organisation - the Instituto Gulbenkian de Ciência

The Instituto Gulbenkian de Ciência (IGC)
is an international biomedical research
and graduate training Institute,
founded and supported by the
Calouste Gulbenkian Foundation,
in Portugal.
This Annual Report covers the Instituto
Gulbenkian de Ciência’s financial year,
from 1st January
to 31st December 2011.

CONTENTS
05
06
12
16
ORGANISATION
THE DIRECTOR'S INTRODUCTION
THE IGC AT A GLANCE
RESEARCH GROUPS
17
18
19
21
23
26
28
30
31
33
34
36
37
38
40
42
43
45
46
47
49
51
52
53
54
55
57
58
59
60
62
64
65
66
67
Protein-Nucleic Acids Interactions − ALEKOS ATHANASIADIS
Plant Stress Signalling - ELENA BAENA GONZÁLEZ
Meiosis and Development − VÍTOR BARBOSA
Epigenetics and Soma - VASCO BARRETO
Variation: Development and Selection - PATRÍCIA BELDADE
Cell Cycle Regulation - MÓNICA BETTENCOURT DIAS
Quantitative Organism Biology - JORGE CARNEIRO
Molecular Neurobiology - DIOGO CASTRO
Population and Conservation Genetics - LOUNÈS CHIKHI
Neurobiology of Action - RUI COSTA
Lymphocyte Physiology - JOCELYNE DEMENGEOT
Plant Molecular Biology - PAULA DUQUE
Cell Biophysics and Development - JOSÉ FEIJÓ
Telomeres and Genome Stability - MIGUEL GODINHO FERREIRA
Collective Dynamics - GABRIELA GOMES
Evolutionary Biology - ISABEL GORDO
Actin Dynamics - FLORENCE JANODY
Epigenetic Mechanisms - LARS JANSEN
Organogenesis - JOAQUÍN RODRÍGUEZ LÉON
Systems Neuroscience - ZACHARY MAINEN
Patterning and Morphogenesis - MOISES MALLO
Early Fly Development - RUI GONÇALO MARTINHO
Development, Evolution and the Environment - CHRISTEN MIRTH
Behavioural Neuroscience - MARTA MOITA
Infection and Immunity - MICHAEL PARKHOUSE
Disease Genetics - CARLOS PENHA-GONÇALVES
Computational Genomics - JOSÉ PEREIRA LEAL
Behaviour and Metabolism - CARLOS RIBEIRO
Complex Adaptive Systems and Computational Biology - LUÍS ROCHA
Inflammation - MIGUEL SOARES
Evolution and Development - ÉLIO SUCENA
Host-microorganism Interactions - LUÍS TEIXEIRA
Evolutionary Genetics - HENRIQUE TEOTÓNIO
Innate Behaviour - MARIA LUÍSA VASCONCELOS
Bacterial Signalling - KARINA XAVIER
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107
120
122
123
135
136
165
171
172
102
103
124
126
127
131
133
166
169
Library
Equipment Purchasing and Maintenance
Administration and Accounts
Ethics Committee
RESEARCH STRUCTURES
PUBLICATIONS
PRIZES AND HONOURS
BUDGET OVERVIEW
GRADUATE TRAINING AND EDUCATION
PhD Programme in Integrative Biomedical Sciences (PIBS)
PhD Programme in Computational Biology (PDBC)
Gulbenkian/Champalimaud International Neuroscience
Doctoral Programme (INDP)
Programme for Advanced Medical Research
- Doctoral Programme for Physicians
GTPB - The Gulbenkian Training Programme in Bioinformatics
THESES
SEMINARS, WORKSHOPS AND MEETINGS
PUBLIC ENGAGEMENT IN SCIENCE
Science Communication and Outreach
Fundraising
PARTNERS AND SPONSORS
ACKNOWLEDGEMENTS
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82
84
69
71
73
74
75
77
78
79
81
85
87
88
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91
92
94
95
97
99
100
101
RESEARCH FELLOWS
Biophysics and Genetics of Morphogenesis - FILIPA ALVES
Plant Genomics - JÖRG BECKER
Network Modelling - CLAUDINE CHAOUYIA
Lupus and Autoreactive Immune Repertoire - CONSTANTIN FESEL
Neuronal Structure and Function - INBAL ISRAELY
Neuroethology Laboratory - SUSANA LIMA
Antigen Presentation and T cell Activation - ELISABETTA PADOVAN
Learning Laboratory - JOSEPH PATON
Immune Regulation - CARLOS TADOKORO
EXTERNAL ASSOCIATED RESEARCH GROUPS
FACILITIES AND SERVICES
Animal Facilities
Transgenics Facility
Plant Facility
Cell Imaging Unit
Genomics Unit
Gene Expression Unit
Histology Unit
Ion Dynamics Facility
Bioinformatics and Computational Biology Unit
Portuguese Bioinformatics Centre
Research Funding Affairs
Innovation and Technology Office
Informatics

ORGANISATION
CALOUSTE GULBENKIAN FOUNDATION
The Calouste Gulbenkian Foundation is a Portuguese private institution of general
public utility created by the will of Calouste Sarkis Gulbenkian, who established its
initial capital, and defined its statutory goals: "charity, art, education and science".
The Foundation’s statutes were set up in 1956.
The Foundation actively pursues its statutory aims in Portugal and abroad,
through a wide range of direct activities and grants supporting projects and
programmes. The Foundation has an orchestra and a choir, organises solo and
collective exhibitions in its museums and exhibition spaces. It also organises
international conferences, meetings and workshops, awards scholarships and
subsidies for specialist studies in Portugal and abroad, and supports programmes
of scientific, artistic and social natures.
BOARD OF TRUSTEES
EMÍLIO RUI VILAR
Chairman
MIKHAEL ESSAYAN
Honoraray Chairman
DIOGO DE LUCENA
Trustee
EDUARDO MARÇAL GRILO
Trustee
ISABEL MOTA
Trustee
MARTIN ESSAYAN
Trustee
TERESA GOUVEIA
Trustee
ANDRÉ GONÇALVES PEREIRA
Non-executive Trustee
ARTUR SANTOS SILVA
Non-executive Trustee
EDUARDO LOURENÇO
Non-executive Trustee
INSTITUTO GULBENKIAN DE CIÊNCIA
SCIENTIFIC ADVISORY BOARD
The Scientific Advisory Board of the IGC oversees the scientific progress, graduate
programmes, recruitment and overall performance of staff and research groups.
The Scientific Advisory Board also advises the Board of the Calouste Gulbenkian
Foundation on all matters of relevance to the mission of the Institute.
SYDNEY BRENNER (The Salk Institute, USA)
Chairman
JONATHAN HOWARD (University of Cologne, Germany)
MARTIN RAFF (University College London, UK)
GINÉS MORATA (Universidad Autónoma de Madrid, Spain)
NICOLE LE DOUARIN (Academie des Sciences, France)
DAVID SABATINI (New York University, USA)
KAI SIMONS (Max Planck Institute for Molecular Cell Biology and Genetics,
Dresden, Germany)
SUSUMU TONEGAWA (Massachusetts Institute of Technology, USA)
RICHARD AXEL (Columbia University, USA)
JEAN−PIERRE CHANGEUX (Pasteur Institute, France)
TERRENCE SEJNOWSKY (The Salk Institute, USA)
IGC DIRECTOR
ANTÓNIO COUTINHO
IGC DEPUTY DIRECTOR
JOSÉ MÁRIO LEITE
DEPUTY TO THE DIRECTOR
JOCELYNE DEMENGEOT

THE DIRECTOR'S
INTRODUCTION
“While unanimously recognised as the epic poet in Portuguese literature, Luis
de Camões wrote many a love poem that most of us, locals, learned by heart
when coming of age. In a beautiful sonnet, Camões explains why Jacob submitted
to serve Rachel’s father for a whole seven years: he wanted Rachel as a
reward and, for that highest goal, was ready to serve for yet another 7 years.
Interestingly, Camões gives no hint as to Jacob’s performance, as if his full dedication
sufficed to qualify him as deserving. Writing the 7th annual report of the
Instituto Gulbenkian de Ciência, I feel I must invoke the same benevolence in
judgment, for full dedication there was in attempting to establish material and
intellectual conditions for the practice of good Science, to strengthen biomedical
research and education in Portuguese institutions, to bring scientific values
to the daily concerns of citizens and politicians. These were the missions that
the Board of Administration of the Calouste Gulbenkian Foundation chose for
this period of IGC’s life, and, looking back, I must say that the Institute has
walked some ground in these seven years. And I must add that, in my metaphor
of Camões’ sonnet, Jacob was not one but many, all of us shepherds and apprentices
dreaming of our Rachel, ready to offer the best we have, in generosity
and commitment, let alone our thoughts and minds.”
This was the first paragraph in the text I wrote for the IGC’s 2005 Annual Report.
Some of my colleagues and I have now served Laban for yet another seven
years, “never serving him but her”, as the poet says. Our Rachel is none other
than Science itself. Laban has been a good master to serve, however: what an
exceptional venture to be associated with this endeavour of reconstructing
the IGC, with the help of a Scientific Advisory Board that is exceptional in all
respects, and with the support, understanding and trust of the Foundations’
Board of Administration. The Institute flourished and accumulated honours and
distinctions, excellent applications from students and scientists, grants, papers
and citations. All this, I am certain, just because the IGC managed to attract outstanding
people of all sorts, who made the Institute their home and, together,
IGC ANNUAL REPORT ‘11
THE DIRECTOR'S INTRODUCTION
6

established a unique and diverse human and intellectual environment. Above
all, the IGC continued to be a joyful place where we all feel well and wish to
be, where diversity, freedom and mutual respect, often friendship but always
warmth, generate intellectual challenge; where the complementarity of interests
fosters cooperation to reach higher and more interesting forms of doing
science together. My younger colleagues will continue for further seven year
periods; sadly for me, but perhaps gladly for the IGC, I shall now serve Rachel
with other Labans. The IGC must reach a yet higher level of excellence and international
reputation, and such new missions require a new operational model,
renewed adaptation to the national and international scientific context, novel
ideas and better practices, in short, a fresh start and a better person to lead the
process of a new reconstruction.
The Board of Administration of the Calouste Gulbenkian Foundation established
the IGC 50 years ago as an instrument to pursue one of the Foundation’s four
statutory goals: Science. If other Foundations and private organisations have
started and maintained research institutes, few have shown an equivalent wisdom:
the Foundations’ Board decided to restructure the IGC at an approximate
rate of once every 15 years. This is an excellent management principle, particularly
for a Science Institute: rather than “keeping going” and getting old,
perhaps bored, with missions that were once relevant, in an operational model
that was once appropriate, the IGC has been reformed several times, and several
times was it reborn from the ashes of the previous structure. Every time,
the expectation is that the Phoenix will rise again, bright gold and scarlet in
colours as the one before. Yet, if the Phoenix is the ultimate example of trust
in the future, there is always a risk that it will not resurrect. All the greater the
joy when it does: the cry of the Phoenix is said to be a most beautiful song.
Being the heralds of innovation in society, however, private foundations must
not fear to take risks. Time has come for yet another such ritual, but this time
of a very special kind. The Board of Administration of the Calouste Gulbenkian
Foundation has decided to attribute to the IGC a novel statute of autonomy. In
the words of its Chairman, Emílio Rui Vilar, at the celebration of the anniversary
in 2011, the scientific model and the mission that were committed to the IGC in
1998 ended their cycle, such that it is time to define a new scientific model and
delineate a novel, perhaps more focused mission. Autonomy will allow for “more
flexibility and better adaptation of the management to a research institute, and
it will reinforce the possibility of establishing partnerships with similar institutions”,
not forgetting “exploring patents and launching start-ups, in a logic of
downstream development of the scientific work.” Risky at it may be, this is a
very exciting time, and we are all profoundly indebted to the Foundation for
the decision, and for the trust in all of us at the Institute that such a decision
implies. With the continuing, even reinforced support of the Foundation, the IGC
will live on, taking on and certainly fulfilling novel missions... for the coming 15
years or so. Would the Institute produce excellent science, would it be competitive
to attract the right people, investigators, technicians, students and support
personnel, would it be able to bring in the necessary external funding, then it
will surely live on, “bright gold and scarlet in colours” for the good of Science, of
this country and of the Foundation’s prestige. I have little doubt that the “new
IGC” will be a tremendous success.
The Institute flourished and accumulated
honours and distinctions, excellent applications
from students and scientists, grants,
papers and citations. All this, I am certain,
just because the IGC managed to attract
outstanding people of all sorts, who made
the Institute their home and, together, established
a unique and diverse human and
intellectual environment.
The Board of Administration of the Calouste
Gulbenkian Foundation has decided to attribute
to the IGC a novel statute of autonomy.
In the words of its Chairman, Emílio Rui
Vilar, at the celebration of the anniversary
in 2011, the scientific model and the mission
that were committed to the IGC in 1998 ended
their cycle, such that it is time to define a
new scientific model and delineate a novel,
perhaps more focused mission.
The “original habitat” of the Phoenix is said to be somewhere between India
(where Garuda was born) and the Fertile Crescent, where agriculture and cities
were once invented; perhaps in Phoenicia, where Cadmus imagined the alphabet
that he later spread while looking for Europa. Rachels, Europas and Phoenixes,
alphabets, kidnappings and rebirths, always this constant wish to explain the
world and ourselves, to understand, to bring to all others the unique liberation
that is knowledge; always this constant drive to create and invent, to derive
new forms of living together. Edward O. Wilson’s last book has raised much
controversy amongst colleagues. Yet, few would argue against the notion that
fitness increases afforded by “societies” (groups of individuals) result in the
unique expansion of the (few) species that show this type of supra-individual
organisation, such that these have taken over the Earth. Wilson concentrates on
the eusocial insects and humans, suggesting that such a “major” evolutionary
transition is quite recent. Cooperation, mutualism, eusociality, altruism, common
goods, “tragedy of the commons”, “cheaters”, policing mechanisms, and
many other terms and notions are loaded with anthropocentric ways of looking
at the world. These were essentially all taken from economic theory, concerned
with analysing the ways by which humans, but not other organisms, trade goods;
IGC ANNUAL REPORT ‘11
THE DIRECTOR'S INTRODUCTION
7

the relationship of these with the reproductive success of individuals, however,
is unclear to say the least, such that there is little biology at the origin of those
terms and notions. Thus, we very well know that “cooperation” is the essence
of life from its very inception, chemical cooperation in this case. Many examples
of collective “behaviour” are already available in bacteria, some of which
can be seen as “cooperative”, for they configure conditions in which individuals
differentially provide for a range of common goods that are “exchanged” for
mutual benefit. If “purposeless” genetic variability in populations of unicellular
organisms is the solution for the unknown future, it also generates standing
genetic variation in the populations, that is, it creates the “differentiation” of
individuals, however rare the variants may be. As one of my bright young colleagues
puts it, if purposeless diversity is the solution for the unknown future,
the differentiation of individuals is the rule of nature. Large populations may
accumulate many such “differentiated” mutants, all the more so as beneficial
mutations are far more frequent than anticipated, in bacteria, yeast, worms and
flies, at least. Hence, even rare variants may reach considerable representation
in the population. Should one of these produce a “common good”, the whole
population profits, changing environments, naturally modulating the relative
frequency of each “sub-type”. The greater the diversity, the higher the chance
for the emergence of new “common goods”, that is, for cooperation. This does
not infringe Hamilton’s rule, for the populations must remain highly related, as
a condition to use the new “common good”. As Maynard Smith had told us, all
“major transitions” in the ways of being alive have been of a cooperative nature,
such that biologists do have an acute sense of the advantages, of the “fitness
increases”, that are afforded by “sharing” with others any given particular way
of living. If I were to pick one single item from the “ethos” catalogue of the
IGC, I would certainly choose “cooperativity” for all that it implies. Diversity, to
start with, for identical individuals gain little in being together, if we are looking
for “emergent novelty”; the group may gain, particularly if individuals are
submitted to a stringent rule, in (biological) brave new worlds of alphas, betas
and gammas, but those are not the kind of worlds we are after. Naturally, each
IGCer takes a lot from many of the others, as she or he provides various kinds
of “goods” to many of the others. If looking at a single variable “good”, we may
identify those that take more than give, and some would speak of “cheaters”.
However, the “cheaters” for a particular “common good” may well be the most
altruistic for another. In short, the “tragedy of the commons” seems more apparent
than real, again solved by the diversity of individuals. This must be true,
as there is little or no “policing”, few rules, and yet, there are no cheaters at the
Institute. Only because, I would think, we do have a common goal that goes well
beyond the diversity of individual interests.
The last year at the IGC was most successful for many of my colleagues. Over
150 publications have appeared in the international scientific literature with an
affiliation to the IGC, many in the most cited journals in the respective fields:
this was the year in IGC’s life with a highest number of publications (some 1,700
for its whole 50 years of life, with over 1,100 since the last reform). For the first
time in its history, citations of work done at the IGC have reach over 4,000/year
(more than 30,000 citations from its foundation, over 20,000 of which for work
published since 1998). IGC’s scientists gained several prestigious international
grants and awards, and they were joined in this success by IGC’s alumni who are
now at other Portuguese institutions. Given the IGC’s mission of educating or “importing”
and then “incubating” the best young scientists, only to “export” them to
other Portuguese institutions, this is a most rewarding outcome. The numbers for
the last five years help to reveal the IGC’s role in the revolution of Life Sciences
in Portugal. For example, thus far, a total of 18 European Research Council grants
were awarded to scientists working in Portugal, 11 of which in Life Sciences: 10 of
these 11 were given to investigators who are or have been at the IGC. If the Life
Sciences appear as the most competitive research area in Portugal, therefore,
this is largely due to IGC’s alumni. Similar results can be seen with programmes of
other international funding agencies: the recent Howard Hughes Medical Institute
“International Early Career Scientists”, the Human Frontiers Science Programme,
and the Bill & Melinda Gates Foundation “Grand Challenges”. In short, the IGC has
contributed to 20 of 23 such grants given to scientists in Portugal. The Institute
itself has also been recognised: the IGC was awarded an Honorary Membership of
the Ordem de Sant'Iago da Espada, by the President of the Portuguese Republic,
received the Oeiras Medal of Honour, the highest attributed by the Municipality,
and for the second consecutive year, the IGC was ranked by “The Scientist - Faculty
of a 1,000” as one of the 10 best places for post-docs to work outside the USA.
Thus, we very well know that “cooperation”
is the essence of life from its very inception,
chemical cooperation in this case.
Many examples of collective “behaviour”
are already available in bacteria, some of
which can be seen as “cooperative”, for
they configure conditions in which individuals
differentially provide for a range
of common goods that are “exchanged” for
mutual benefit.
The greater the diversity, the higher the
chance for the emergence of new “common
goods”, that is, for cooperation.
If I were to pick one single item from the
“ethos” catalogue of the IGC, I would certainly
choose “cooperativity” for all that it
implies.
IGC ANNUAL REPORT ‘11
THE DIRECTOR'S INTRODUCTION
8

After all these years of a half-distant concern with “biomedical sciences”, rather
than just with immunology in my own group, I have learned many things, but
certainly much fewer that I would have wished. If I were to attempt any sort of
“wins and losses balance” of having engaged in science administration, I see
mostly “wins”. The first and foremost “win” would be to have had the opportunity
to enlarge the field of my own scientific exposure, with the necessary consequence
of a continuous wonder with nature. Particularly when, as Pierre Teillard
de Chardin wrote, “facts are illuminated by evolution, the trajectory which all
lines of thought must follow”, and we thus gain a glimpse of understanding:
not just of the genetic, molecular, cellular and systemic mechanisms, but of life
itself and what is to be alive on this planet. Better than I could do, Feynman
wrote “The world looks so different after learning science. For example, trees
are made of air, primarily. When they are burned, they go back to air, and in
the flaming heat is released the flaming heat of the sun which was bound in to
convert the air into tree... These things are beautiful things, and the content of
science is wonderfully full of them. They are very inspiring, and they can be used
to inspire others.” The pleasure of understanding for the first time is a feeling
that we all have had; when it follows many years of attempts, of hypotheses,
of hunches, of hard work, then it reaches unique levels, particularly when the
reasonable doubt is exceedingly small. With two additional gains: most often,
such a novel understanding is a critical piece in the wider consideration (and
wish to understand) of something else, for yet more concerns, but also for more
excitement; then, each of those incremental steps of understanding represents
the objective reality of progress that only science can give: that problem “is
done” and we can go on to further questions.
Over 150 publications have appeared in
the international scientific literature with
an affiliation to the IGC, many in the most
cited journals in the respective fields: this
was the year in IGC’s life with a highest
number of publications (some 1,700 for its
whole 50 years of life, with over 1,100 since
the last reform).
The next mark is an ever-increasing attachment to diversity of individuals and
populations, humans, first of all, but also of all other living beings. The wonder
of life is so present and the fascination of understanding so great that sometimes
one feels that this should be shared by anyone who wishes to have it, and
be instituted as one more “human right”. On those occasions, you cannot avoid
thinking of all those in the world who, because they were born where there is
also no access to running clean water, to proper health care and education, are
excluded from the possibility of contributing to the future of the world, that is,
of being scientists. Knowing that scientists solve problems, I also worry about
all those large numbers of possibilities that we are giving away by excluding so
many brains from science. All the more so as those brains are quite different
from most of those who are already in science, and they may well look at problems,
imagine and see solutions in very novel, “unconventional” manners, as a
result of their cultures. Their exclusion from the science enterprise is certainly a
major concern for the future, but also a strong reason to feel optimistic, would
we come round to solving it. Sometimes, glimpses of understanding of the tremendous
power of evolution – enough to generate human brains starting with
beautiful, yet modest, bacteria – and of its most robust principles, also brings
the wish to extend such principles to the understanding of human societies and
the “government of the city”. As above, “They [the contents of science] are very
inspiring, and they can be used to inspire others.” I guess that many have experienced
this wish before, and I am ever surprised by the rarity of contributions
from serious scientists to politics. As some of my colleagues at the Institute
keep reminding me, science is the only human activity, which has developed
a method to describe, understand and “organise” the world that, at least in
theory, is independent of the individual. As a common enterprise, science also
ensures the respect of all individuals, yet confronting divergent opinions, in a
socially “self-organised manner”.
Last but not least, another mark concerns not science but how to do it. With
some colleagues of my generation, I share the opinion that, coming to our
retirement, we will leave research in much worse condition than we found it,
particularly on ethical terms. I am not speaking of science itself, but of the
way we do it. “Doing science”, when we started, was a common enterprise of
friends, with respect, often admiration, for older or younger, also with emulation,
sometimes competition, always fair and in all openness amongst people of
the same trade, endowed with the same deep conviction that science can only
be done this way. At least, this was the way we felt. To disrespect peers, be that
by secrecy, unprepared bad judgment or unfair competition, amounted to disrespecting
ourselves. Göran Möller, my Thesis supervisor, never finished writing
a paper without preparing 60 copies in the lab’s stencil machine to send to his
best competitors and friends, simultaneously with submitting it to the journal
As some of my colleagues at the Institute
keep reminding me, science is the only human
activity, which has developed a method
to describe, understand and “organise” the
world that, at least in theory, is independent
of the individual. As a common enterprise,
science also ensures the respect of all
individuals, yet confronting divergent opinions,
in a socially “self-organised manner”.
IGC ANNUAL REPORT ‘11
THE DIRECTOR'S INTRODUCTION
9

for publication. For, as he said, it is our duty to the science community to let all
others know of what we found and what we think, the sooner the better. The
excitement with reading the referees’ comments was genuine, concerned with
evaluating how our ideas were accepted, discovering ways of how to improve
our papers. Of course, papers were also rejected at the time, and of course,
we also quite often got upset; but for our misses, rather than for the unfairness
of referees, whom we trusted were doing the best they could. Things have
changed, indeed. As if most colleagues would be more concerned with their own
success, reputation, career or income, than with science itself. As if many would
not care about the means to reach their personal goals. The most worrisome
part of all this evolution, over the last three decades or so, is the danger that
science will no longer be a school of human virtues, a common enterprise of
rigor, criticism and tolerance. We must solve the problem and reverse this trend;
otherwise, the best people in the younger generations will soon recognise this
state of affairs and science will no longer attract them. And with no role models
to look up to, younger scientists will be left in a desert of ethics, where cutthroat
competition will prevail as the law. Looking at young science beginners
today, I most often miss the careless enthusiasm that those in my generation
had; I see instead a grave concern with “career plans”, precisely something we
never had. I am truly sorry for them and I feel that it is our responsibility to try
to explicit the mechanisms that brought us down this path of declining ethics.
The solution and how to implement it, however, cannot be left in the hands of
the very “old amateurs” who let it all happen as it did; this can only be done by
the younger generations.
I am certain that the principal mission of
the IGC, while producing excellent science
and educating the younger generation to
do it, is to remain a place where, whatever
happens, that way of “doing science” will
live on and will continue to attract the best
minds and the best characters.
I am certain that the principal mission of the IGC, while producing excellent science
and educating the younger generation to do it, is to remain a place where,
whatever happens, that way of “doing science” will live on and will continue to
attract the best minds and the best characters.
ANTÓNIO COUTINHO
Director
Oeiras, May 2012
Note added in proof:
Jonathan Howard has now been formally appointed Director of the IGC by the
Board of Administration of the Calouste Gulbenkian Foundation, to take effect
from October 1st, 2012. I have no doubts that there is no better person for this
task. All of us at the Institute are very pleased with the decision and grateful
to Jonathan Howard that he has accepted the challenge. We are sure that the
Phoenix will rise again.
IGC ANNUAL REPORT ‘11
THE DIRECTOR'S INTRODUCTION
10

IGC ANNUAL REPORT ‘11
THE DIRECTOR'S INTRODUCTION
11

THE IGC AT A GLANCE
The Instituto Gulbenkian de Ciência (IGC) is an international biomedical research
and graduate training institute, dedicated to promoting multidisciplinary science
of excellence and a new generation of scientific leaders.
The IGC operates as a host institution that provides an entrance hall into Portugal
for national and international researchers and clinicians, with a view to setting
up and developing research programmes of excellence and strengthening the
scientific community, both nationally and internationally.
The IGC mssions are thus:
• To identify, educate and incubate new research leaders, providing state-
-of-the-art facilities and full financial and intellectual autonomy to pursue
research projects;
• To export new leaders in biomedical research to research centres and academia
in Portugal and internationally;
• To provide international graduate teaching and structured training programmes;
• To promote the values of science in society, scientific literacy, and the
active participation of citizens in scientific research, through engagement
with different communities and stakeholders;
• To foster technology transfer, intellectual property (IP) licensing and commercialization
and start-ups.
The IGC was set up by the Calouste Gulbenkian Foundation, a Portuguese private
institution of general public utility, in 1961.
The institute is part of the Oeiras Campus, home to several other basic and applied
research centres in biology, biotechnology and chemistry, including the
Associated Laboratory ITQB, made up of the IGC, the Instituto de Tecnologia
Química e Biológica (ITQB) the Instituto de Biologia Experimental e Tecnológica
(IBET) and the Centre for the Study of Chronic Diseases (CEDOC).
Since 1998, the IGC has hosted 77 research
groups; 36 of these have moved on to other
research institutes, 31 to research centres
in Portugal.
37 research groups in Portugal are IGC-associated
groups, with access to IGC facilities
and services.
The IGC pioneered graduate training in
Portugal. Since 1993, 6 PhD Programmes
have been set up, with approximately 80
speakers/year/programme;
By October 2011, 540 PhD students had
started their science education at the IGC
in programmes and research groups;
A worldwide network of over 350 Gulbenkian
alumni hold regular meetings.
RESEARCH
Research at the IGC is organism centred, hypothesis driven, integrative and multidisciplinary
in approach. The focus is on the genetic bases of development
and evolution of complex systems, spanning the following areas:
• Evolutionary biology
• Cell biology, cell cycle, DNA repair and ageing
• Inflammation, immunity and auto-immunity
• Host pathogens interactions
• Developmental biology in animals and plants
• Genetics of complex diseases: malaria, diabetes Type I, lupus
• Behavioural neuroscience
• Theoretical and computational biology
IGC PEOPLE
In 2011*:
368 People work at the IGC
• 33 Average age
30 Nationalities
• 275 Portuguese
• 95 Rest of the World
318 researchers (does not include
facilities or services staff)
144 PhD holders
• 35 Principal Investigators
18 Portuguese
17 Rest of the World
17 Female
18 Male
• 9 Research Fellows
• 11 Facility/Service Heads & Staff
• 89 Post-docs
93 PhD students (not including
1st year students)
44 Technicians
31 Trainees
22 Facilities/Service Staff
4 Visiting scientists
13 Masters Students
17 Administrative Staff
4 PhD Programmes
35 Research Groups
9 Research Fellows
2 new Research Fellows
4 departing research groups
*As of December 2011.
IGC ANNUAL REPORT ‘11
THE IGC AT A GLANCE
12

30 Nationalities working at the IGC
1
1
1
10
1
1
1
1
Angola
Argentina
Belgium
Brazil
Bulgaria
Colombia
Denmark
Estonia
14
7
3
1
4
1
4
2
France
Germany
Greece
Hungary
India
Israel
Italy
Japan
4
1
5
2
4
275
1
1
Lituania
Luxemburg
Mexico
Netherlands
Poland
Portugal
Romania
Serbia
7
1
1
1
6
9
Spain
Sweden
Switzerland
Turkey
United Kingdom
USA
IGC ANNUAL REPORT ‘11
THE IGC AT A GLANCE
13

SCIENTIFIC COMMUNICATION
In the last 5 years:
655 Scientific Publications (Source: Web of Science)
In 2011:
154 Peer-reviewed publications
3 Book chapters
3 Proceedings
Published Items with IGC address in each Year.
(Source: Web od Science, May 2012)
Citations to IGC papers in each year.
(Source: Web of Science, May 2012)
6 PhD Theses
7 MSc Theses
173 International presentations by IGC researchers
193 Seminars at IGC
• 107 External speakers
15 Conferences, Meetings, Workshops at IGC
COMPETITIVE AWARDS SECURED BY IGC RESEARCHERS
11 Prizes and Honours, including:
• 1 The Scientist - Faculty of 1000 Best Places for Post-docs Award
• 1 Honorary Membership of the Ordem de Sant'Iago da Espada, Portugal
• 1 Roche Organ Transplantation Research Foundation (ROTRF) Recognition Prize
• 2 Gold Medals of Merit, Oeiras City Council (Portugal)
• 1 Ciencia en Acción - Teaching Resources 1st Place, Ciencia en Acción (Spain)
• 5 Nominations for Editorial Boards
Since 1998, around 4,000 scientists have
given talks and/or lectures at the IGC.
Around 120 conferences, meetings and workshops
have been held.
The IGC was ranked amongst the '10 Best
Places for Post-docs' outside the USA, by
The Scientist - Faculty of 1000' for two
years in a row - in 2010 and 2011.
34 new research grants:
• 1 European Research Council Starting Grant (ERC)
• 2 European Commission Framework Programme 7 (FP7)
• 1 Association for International Cancer Research - AICR
• 1 Wellcome Trust (UK)
• 18 Fundação para a Ciência e a Tecnologia - FCT (Portugal)
• 4 Fundação Bial (Portugal)
• 2 Oeiras City Council (Portugal)
• 2 Luso-American Foundation for Development - FLAD (Portugal)
• 1 Associação Viver a Ciência - Simbiontes (Portugal)
• 1 QREN - PORLisboa (Portugal)
• 1 Sociedade Portuguesa de Diabetologia/Novo Nordisk (Portugal)
And also:
• 2 AXA Research Fund Post-Doctoral Fellowships (France)
• 1 Volkswagen Foundation Meeting Support Grant (Germany)
• 1 Sociedade Portuguesa de Imunologia Travel Grant (Portugal)
IGC ANNUAL REPORT ‘11
THE IGC AT A GLANCE
14

2004 - 2011
NEW RESEARCH GRANTS BREAKDOWN BY SOURCE OF FUNDING
Total grants is 277
(Source: IGC Research Funding Affairs)
FCT (Portugal) PUBLIC
EUROPEAN COMMISSION PUBLIC
OTHERS PUBLIC
OTHERS PRIVATE
OTHERS PRIVATE-PUBLIC PARTNERSHIP
TOTAL
Since 2007, half of the European Research
Council Grants awarded to life science researchers
working in Portugal have gone
to IGC scientists (6 out of 11, with a further
3 grants going to alumni of the Gulbenkian
PhD Programme in Biology and Medicine).
2004 - 2011
PROPORTION OF RESEARCH GRANTS BREAKDOWN BY FUNDING SOURCE
Total grants is 277
(Source: IGC Research Funding Affairs)
4%
59%
11%
9%
Since 2004, IGC researchers have secured
just under 300 project grants, from national
and international funding agencies,
including EU Framework Programmes, European
Research Council, Howard Hughes
Medical Institute (USA), Bill & Melinda
Gates Foundation (USA), Human Frontiers
Science Programme.
17%
FCT (Portugal) PUBLIC
EUROPEAN COMMISSION PUBLIC
OTHERS PUBLIC
OTHERS PRIVATE
OTHERS PRIVATE-PUBLIC PARTNERSHIP
IGC ANNUAL REPORT ‘11
THE IGC AT A GLANCE
15

RESEARCH
GROUPS

PROTEIN-NUCLEIC ACIDS
INTERACTIONS
Alekos Athanasiadis Principal Investigator
PhD in Structural Biology, University of Crete, 1995
Postdoctoral Fellow, ICGEB/Unido
Postdoctoral Fellow, Massachusetts Institute of Technology, USA
Research Scientist, Massachusetts Institute of Technology, USA
Principal Investigator at the IGC since 2009
Sequence is not fate. Proteins demonstrate a fundamental ability not only to
recognise and bind to specific pieces of nucleic acid code but also to alter
its information content by catalysing reactions that rearrange its sequence or
specifically change one nucleotide for another. We study the molecular details
and the fundamental concepts that drive these intimate interactions between
the major biological macromolecules.
RECOGNITION OF FOREIGN NUCLEIC ACIDS IN INNATE IMMUNITY
For vertebrates, innate immunity represents the front-end of their defence
against invading viruses and bacteria. Central in the pathogen recognition process
is the detection of foreign nucleic acids. However, exactly how foreign
nucleic acids are distinguished from self DNA and RNA is poorly understood
and of great importance since false recognition leads to severe auto-immune
disorders. DAI is a protein that was recently identified as a receptor for dsDNA
in the cytoplasm and is a member of a family of proteins involved in interferon
mediated antiviral responses that share a DNA/RNA binding domain that
specifically recognises the left-handed form of nucleic acids helices known as
Z-DNA/Z-RNA. Our aim is to biochemically and structurally characterise the proteins
involved in this interferon response pathway that includes, besides DAI,
the vertebrate specific RNA editing enzyme ADAR1, as well as viral inhibitors of
this pathway found in Pox and Herpes viruses.
In 2011 we determined the structure of a Herpes virus inhibitor of interferon
response that employs the same DNA binding domain found in DAI, the Zalpha
domain at 1.76A resolution, and show for the first time that Zalpha domains can
form dimers through domain swapping (Manuscript in preparation). We have
managed expression of different DAI constructs and obtained preliminary crystals
for some of them with nucleic acids.
A TO I RNA EDITING AND MOLECULAR EVOLUTION
The A to I RNA editing post-transcriptional modification of RNAs is widespread
in all animal species, affecting transcripts of thousands of genes. Often such
modifications are found in coding sequences where they can alter the sequence
of the encoded protein. Targeting of the modification is directed by intronic sequences
that act as guide RNAs. Understanding how this intron encoded modification
alters the rates and direction of protein coding gene evolution is the
aim of this project. Our study is based on simulations of the evolution process
in the presence of RNA editing and the comparative analysis of genes known
to undergo editing through evolution. At the same time we develop methods
for the detection of editing sites in transcript sequences and the prediction of
editing sites based on the genomic sequence.
GROUP MEMBERS
Matteo de Rosa (Post-doc)
Diogo Ribeiro (Masters Student; started in September)
Sónia Zacarias (Masters Student; started in August)
Krzysztof Kus (PhD student; started in October)
Ana Rita Tomé (Research Assistant; left in July)
Theokliti Tsigkri (Research Assistant; left in August)
COLLABORATORS
Maas Stefan (Lehigh University/NIH, USA)
Rich Alexander (Massachusetts Institute of Technology, USA)
Maria Arménia Carrondo (ITQB - Instituto de Tecnologia Química e Biológica,
Portugal)
FUNDING
FP7 Marie Curie International Reintegration Grant, European Commission
Fundação para a Ciencia e Technologia (FCT), Portugal
Instituto Gulbenkian de Ciência, Portugal
Crystals of the herpes virus protein Orf112 developed at IGC.
Crystal structure of Orf112 at 1.76Å resolution based on data measured at ESRF/
Grenoble. The tetrameric structure is formed by two domain swapped monomers.
In 2011 we developed the software platform for the simulation of gene evolution
in the presence of RNA editing. We have already explored a wide range of parameters
in this simulation and demonstrate that RNA editing can significantly
impact the evolutionary rates resulting in acceleration or delay, depending on
the efficiency of the editing process (Manuscript in preparation).
Simulations show accelerated rates of evolution in the presence of RNA editing
at low editing efficiency.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
17

PLANT STRESS
SIGNALING
Elena Baena González Principal Investigator
PhD in Plant Physiology and Molecular Biology, University of Turku, Finland, 2002
Postdoctoral Fellow, Massachusetts General Hospital, Department of Molecular Biology, Boston, MA, USA
Principal Investigator at the IGC since 2008
Environmental stress (drought, shading, cold, salinity, pollutants) has a great
impact on plant growth and developmental decisions. Under stressful conditions
energy production through photosynthesis and/or respiration is reduced,
causing an energy deficit in the cell and subsequent growth arrest. Work in
our laboratory focuses on the SnRK1 signalling cascade, central to the sensing
of stress-triggered energy deprivation and to the subsequent orchestration
of gene expression changes and enzyme regulation necessary for recovery
and adaptation. Our goal is the dissection of this key pathway and the deeper
characterisation of the cellular processes under SnRK1 control as a first step to
understand how stress cues are translated into growth and developmental decisions
that contribute to stress tolerance and adaptation. We use Arabidopsis
thaliana as a model and a combination of cell-based assays, functional genomics,
biochemistry, and genetics.
THE ROLE OF miRNAs IN PLANT ENERGY SIGNALLING
Different types of stress converge in an energy deficiency signal that is translated
into a vast transcriptional response by the SnRK1 protein kinases. The SnRK1-
mediated metabolic switch thereby promotes cell survival and the elaboration of
longer-term growth and developmental responses for adaptation.
GROUP MEMBERS
Ana Confraria Augusto (Post-doc)
Pierre Crozet (Post-doc; started in January)
Leonor Duarte Margalha (PhD student; started in May)
Cláudia Martinho (PhD student)
Mattia Adamo (PhD student; started in November)
Carlos Alexandre Elias (Technician)
Américo Rodrigues (Visiting scientist; started in September)
COLLABORATORS
Jen Sheen (Massachusetts General Hospital, Boston, USA)
Mark Borowsky (Massachusetts General Hospital, Boston, USA)
Brad Chapman (Massachusetts General Hospital, Boston, USA)
Ignacio Rubio Somoza, Detlef Weigel (Max Planck Institute
for Developmental Biology, Tubingen, Germany)
Pedro L. Rodriguez Egea (Instituto de Biología Molecular y Celular
de Plantas, Universidad Politécnica de Valencia, Spain)
Markus Teige, Andreas Bachmair (Max F. Perutz Laboratories,
Univ. Vienna, Austria)
FUNDING
FP7 Marie Curie Reintegration Programme, European Commission
European Molecular Biology Organisation (EMBO), UK
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Marie Curie Initial Training Network, European Commission
Despite the importance of the SnRK1 pathway, it is not known how energydeficiency
information is translated into gene expression changes. Possible
mediators of this response are transcription factors (TFs), some of which have
already been identified. In addition, the signal may be conveyed through micro-
RNAs (miRNAs), which have been implicated in the response to various nutrients
and stresses. Since some of the SnRK1 target genes are known to be regulated
also by miRNAs, we postulate that part of the SnRK1-mediated stress response
is executed through miRNAs and we are currently exploring this hypothesis
employing a combination of cell-based assays, biochemistry and transgenics.
Using plants with impaired small RNA biogenesis we have confirmed that a subset
of SnRK1 targets is indeed repressed through miRNAs, and specific effectors
have been identified through target mimicry-based knocking down approaches.
To understand the biological function and connection to the SnRK1cascade we
are currently characterizing gain- and loss-of-function lines of these miRNAs as
well as of some of their main targets.
NOVEL REGULATORY MECHANISMS OF THE ENERGY SENSOR KINASES
IN ARABIDOPSIS
Regardless of their origin, most abiotic stresses converge as energy-deprivation
signals on the SnRK1 protein kinases (PKs), which promote stress tolerance
and maintain homeostasis through massive transcriptional reprogramming. In
the long-term, the integration of environmental and internal cues through the
SnRK1 system contributes to the optimization of growth and development in an
ever-changing environment.
As a first step to understand how this is accomplished at the molecular level
we seek to gain mechanistic insight into SnRK1 regulation through analysis of
SnRK1 post-translational modification(s) as well as from the identification and
characterisation of the phosphatase(s) that help to reset the system.
Using various heterologous systems we have substantial evidence for the posttranslational
modification of SnRK1 and the residues affected in these assays
have been identified using MS/MS. The occurrence of this modification in vivo is
currently being assessed in various conditions and tissues. In addition, specific
PP2C phosphatases have been identified as negative SnRK1 regulators. These
PP2Cs interact with SnRK1 in Y2H and in plants they inactivate SnRK1 through
dephosphorylation.
The SnRK1 protein kinase integrates environmental stress cues and internal signals
to promote plant stress tolerance and optimise growth and development.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
18

MEIOSIS
AND DEVELOPMENT
Vítor Barbosa Principal Investigator
PhD in Drosophila Genetics, University of Cambridge, UK, 2002
Postdoctoral Fellow, Skirball Institute of Biomolecular Medicine, New York University, USA
Principal Investigator at the IGC since 2009
We study links between meiosis and oocyte maturation. The integrity of meiotic
chromatin in flies is monitored by a checkpoint whose activation affects
gamete polarity. Persistent meiotic double strand breaks activate a conserved
DNA damage response (DDR), which causes dorsal-ventral (DV) polarity defects
in the eggshell. With a panel of germline mutations that cause such defects we
want to:
1. Characterise a new DDR to structural nuclear defects. We have discovered
that an insulator body (IB) component is under surveillance of a new checkpoint;
2. Investigate the role of IBs in oocyte maturation. We focus on oocyte-specific
transcription and on protein interactions in the IBs;
3. Study silencing of selfish genetic elements along oogenesis. Specifically,
we are interested in the conserved PIWI-associated family of non-coding
RNAs (piRNAs). piRNA mutants elicit DDRs specifically in the germ line at
different time points of oogenesis. We created a biased method to identify
piRNA genes.
GROUP MEMBERS
Ana Bernardo (Research Assistant; left in August)
Triin Laos (Research Assistant)
Patrícia Silva (Research Assistant)
Raquel Santos (PhD Student)
COLLABORATORS
Caryn Navarro (Boston University School of Medicine, USA)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
FP7 Marie Curie International Reintegration Grant, European Commission
STUDIES OF CHROMATID COHESION DURING MEIOSIS IN DROSOPHILA
MELANOGASTER REVEAL A NOVEL DNA DAMAGE CHECKPOINT PATHWAY
ESSENTIAL FOR OOCYTE POLARITY
As in vertebrates, Drosophila oocyte differentiation and maturation requires an
ensemble of complex interactions with surrounding cells. Moreover, studying
transcriptional control within the germinal vesicle is partly hindered by meiosisrelated
chromatin remodelling. We show an oocyte-specific localisation of the
cohesion protein dPds5 in foci in mid oogenesis. The dPds5 foci change stereotypically
and are excluded from the meiotic chromatin condensed into a karyosome.
This project aims to understand the oocyte-specific function of dPds5
knowing that to its foci co-localise the insulator body (IB) component CP190.
We ask what are the mechanisms affected by this new nuclear structure. We will
focus on transcription and replication control.
Furthermore, we aim to identify earlier components of the checkpoint that
monitor the meiotic function of dPds5, and define downstream effectors of the
new DDR pathway identified through studies on dPds5 mutants.
dPds5 and CP190 physically interact by immunoprecipitation (IP). The same IPs
from egalitarian (egl) mutant ovaries where oocytes are not maintained show a
significant decrease compared to controls.
RNA synthesis in oocytes occurs in two transcription “bursts”. The latter (in
stage 10) is inhibited in dPds5 mutants. The dpds5 meiotic products show higher
chromatid number compared to controls.
In oocytes dPds5 surveillance requires dATM and dChk2.
DNA DAMAGE CHECKPOINTS ACTIVATION DURING MEIOSIS AND ITS EFFECTS
IN DROSOPHILA OOGENESIS
Ventralisation of the Drosophila egg indicates persistent DNA damage responses
(DDR) to meiotic double strand break (DSB). DDRs activate downstream
“effectors”, which cause incorrect eggshell polarity. What chromatin mechanisms
are under DDR surveillance and what are the “effectors” are our major questions.
We focus on genes of the piwi-interacting RNA (piRNA) biogenesis. piR-
NAs are the major non-coding RNA in transposon element (TE) silencing. Little
is known about the piRNA function as well as the cellular responses to TE amplification.
One response is microtubule acetylation, which causes clumps of motor
complex components such as Bicaudal-D (BicD). We found BicD aggregates
The oocyte nucleus is not arrested during meiotic prophase I. Anterior pole of a
Drosophila egg chamber in stage 7 marked with the insulator body component
CP190 (red), the functional cohesion protein dPDS5 tagged with GFP driven by the
actin promoter (green), and DNA (blue). Whereas polyploidy nurse cells (n.c.) do
not show IBs, the oocyte IBs (arrow) appear far from the condensed chromatin (*),
expand in number during this stage and then disappear.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
19

in known piRNA mutants. We combined eggshell ventralisation with BicD antibody
staining into a screen protocol highly biased toward piRNA mutants. We
will rescreen our collection for new piRNA genes. We will also map the candidate
“effector” troya. The troya phenotype suggests susceptibility for DDR activation.
65% of the lines are screened. Six show Bic-D clumps. We validated positives by
staining for H2Av and by qPCR TEs. All lines with clumps show DDR activation
and TE overexpression. One is allelic to rhino another known piRNA gene. Three
singletons are novel piRNA components as they complement all known piRNA
mutantions on the chromosome. troya show clumps and high TE levels when in
trans with any other 2R mutation in the collection. We mapped troya to a region
with two annotated genes.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
20

EPIGENETICS
AND SOMA
Vasco M. Barreto Principal Investigator
PhD in Immunology, Université Paris VI, France, 2001
Research Associate, Laboratory of Molecular Immunology, The Rockefeller University, USA
Principal Investigator at the IGC since January 2008
Immunoglobulin genes are remarkable in two ways. Unlike almost any other
gene, they undergo a process of somatic editing, rendering each allele from
each maturing B cell unique, and producing antibodies of improved affinity over
the course of an immune reaction. Unlike most other autosomal genes, immunoglobulin
alleles are monoallelically expressed. We study these two phenomena
as part of B cell biology, but our ultimate goals are to address the epigenetic
nature of random monoallelic expression and the impact of DNA editing mechanisms
in a broader context.
ON THE EPIGENETIC NATURE OF IMMUNOGLOBULIN GENE
MONOALLELIC EXPRESSION
In random autosomal monoallelic expression a cell expresses the paternal allele
from an autosomal locus and another cell from the same individual expresses
the maternal allele. This type of mosaicism is reminiscent of X-chromosome
inactivation and it has been suggested that the two processes share epigenetic
marks. Using the heavy and light chain murine immunoglobulin genes as models
for random autosomal monoallelic expression, we have tested whether there is
an imprint in the Ig alleles that, much like X-chromosome inactivation, is established
early in development and is then stably propagated as the cell divides
and becomes a B lymphocyte. Our preliminary data support the notion that
random autosomal monoallelic expression has unique features, not shared with
X- chromosome inactivation.
GROUP MEMBERS
Catarina Cortesão (Post-doc)
Clara Pereira (PhD Student)
Thiago Guzzela (PhD Student)
Inês Trancoso (PhD Student)
Raquel de Freitas (Research Technician; started in August)
Filipa Marta (Research Technician; left in August)
COLLABORATORS
Paulo Vieira (Institut Pasteur, France)
P. Hammarström (Karolinska Institute, Sweden)
Y. Zhao (China Agricultural University, China)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
FP7 Marie Curie International Reintegration Grant, European Commission
A
We have complemented the in vitro data of last year with the analysis of V(D)
rearrangements in in vitro experiments. We have now conclusive evidence that
there are no stable epigenetic imprints in hematopoietic stem cells, but that in
the CLP stage there are transiently stable imprints. One manuscript is in preparation:
Pereira CF, Vieira P., Barreto VM (in preparation) Immunoglobulin Gene
Alleles Rearrange Independently.
AID AND BEYOND
This proposal revolves around the enzyme Activation-Induced Deaminase (AID).
AID plays a pivotal role in adaptive immunity because it underlies the lesions in
the immunoglobulin genes that ultimately lead to somatic hypermutation (SHM),
class switch recombination (CSR) and immunoglobulin gene conversion (Ig GC).
However, its mutagenic ability has a pernicious side effect and AID has been
implicated in B lymphomas and other neoplasias. We study the interactions between
AID and factors that are important for CSR, as well as additional aspects
of the biology of this molecule, such as its role in the germ line.
We have detailed the role of residue S38 in the phylogeny of AID. We have also
shown that AID does not contribute to the frequency of meiotic recombination.
Finally, we have found suggestive evidence for and interaction between AID and
CSR-specific cofactors. Two manuscripts are in preparation (one on AID and CSR
and one on AID and meiotic recombination).
B
C
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
21

A
B
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
22

VARIATION:
DEVELOPMENT
AND SELECTION
Patrícia Beldade Principal Investigator
PhD in Evolution and Development, Leiden University, the Netherlands, 2002
Associate Professor, Institute of Biology, Leiden University, the Netherlands
Principal Investigator at the IGC since 2009
link to external website
My research in evolutionary developmental biology is focused on the mechanistic
basis of phenotypic variation and adaptation. Heritable phenotypic variation
is the raw material for natural selection, and a universal property of biological
systems - including traits of medical importance. Understanding the mechanisms
that generate this variation is a key challenge in biological research. How
does the external environment regulate organismal development to account for
adaptive phenotypic plasticity? What are the gene types (e.g. transcription factors
versus enzymes), specific genes, and gene regions (e.g. regulatory versus
coding sequence) that contribute to evolutionarily relevant variation? How do
they affect development to produce different adult phenotypes? For the dissection
of variation in complex, diversified and ecologically-relevant phenotypes
the lab is currently using two systems: wing colour patterns in butterflies and
caste morphology in ants.
EVOLUTIONARY DIVERSIFICATION:
GENETIC BASIS AND ADAPTIVE SIGNIFICANCE OF VARIATION
IN BUTTERFLY WING PATTERNS
Morphological diversity is the result of the reciprocal interactions between the
developmental processes that translate genotype into phenotype and produce
adult morphologies, and the evolutionary forces that weigh in the performance
of alternative phenotypes to determine their frequency. The project focuses on
butterfly wing patterns to integrate analysis of genetics in a lab model with the
analysis of morphological and genetic diversification across representatives of
different lineages. This type of integrated analysis (from genotypic variation, to
phenotypic variation within-species, to phenotypic diversification across species)
can provide important insights into fundamental issues in evo-devo and
our understanding of morphological diversity. This project analyses different
types of phenotypic variation (quantitative genetic variation and alleles of large
effect) at the ecological (fitness of variant morphologies) and genetic (mapping
and expression analysis) levels.
GROUP MEMBERS
Roberto A. Keller (Post-doc)
Inês Conceição (Post-doc; left in March)
Maria Adelina Jerónimo (PhD student; started in May)
Leila Shirai (PhD student)
Ana Rita Mateus (PhD student)
Filipa Marta (Technician; started in August)
COLLABORATORS
Anthony Long (University of California at Irvine, USA)
Paul Brakefield (Leiden University, The Netherlands)
Tom van Dooren (Ėcole Normale Supėrieure de Paris, France)
Christian Peeters (Université Pierre-et-Marie Curie, France)
Filipa Abreu (Instituto Gulbenkian de Ciência, Portugal)
Vassilis Douris (Leiden University, The Netherlands)
Suzanne Saenko (Leiden University, The Netherlands)
Niklas Wahlberg (University of Turku, Finland)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Speed-dating at Optimus Alive! Festival, Algés, July
Biology in Modern Times Seminar for Teachers,
Instituto Gulbenkian de Ciência, May
Work on this project in 2011 was mostly dedicated to finishing and publishing
work still not published. Specifically, we completed the annotation and comparative
analysis of both protein-coding and non-coding genomic sequence around
eleven genes expressed in developing wings (Conceição et al. PLoS ONE 2011).
The final report, submitted to FCT (National funding agency) was awarded the
top grade, “A”.
THE CONTRIBUTION OF NOVEL GENES TO THE FORMATION
OF EVOLUTIONARY NOVELTIES
The origin and modification of evolutionary novelties (i.e. lineage-restricted
traits such as feathers in birds and wing patterns in butterflies) are key topics
in evolutionary developmental biology. While there is no doubt that conserved
developmental pathways can acquire new functions and be recruited for the
formation of such novel traits, the contribution of genes restricted to specific
lineages remains under-tested. In fact, the popular expression that assigns the
evolution of novelties to “teaching old genes new tricks” might be biased by the
standard approach which studies “shared genes” known in lab models, rather
than identify and pursue "new ones" in non-models. This project will contribute
to overcome this bias and specifically test the involvement of candidate novel
(or highly diverged) new genes in the formation of butterfly wing colour patterns
(evolutionary novelties characteristic of lepidopterans and used in visual
communication).
We completed the in silico sequence analysis of a few hundred candidate novel
genes, (including search for repetitive and coding regions, putative functional
domains, and orthologous genes in public depositories) to generate a short-list
In a paper published in 2011 in the Open Access journal EvoDevo, we report on
a phylogenetic-wide analysis of the expression of the Hox gene Antennapedia
in association with the formation and diversification of a model novel trait. We
show novel patterns of Antennapedia expression in presumptive eyespot organisers
in larval wing discs (before organiser genes Notch and Distal-less) which are
restricted to a particular lineage of eyespot-bearing butterflies.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
23

of ca. 30 candidate genes for expression analysis. For the latter, we have designed
primers and probes and started optimizing semi-quantitative PCR and in
situ hybridisation protocols for analysis of levels and spatial patterns of gene
expression, respectively.
COPING WITH CHANGING ENVIRONMENTS:
GENETIC AND PHYSIOLOGICAL MECHANISMS OF ADAPTIVE PLASTICITY
Phenotypic plasticity is the ability of some genotypes to develop into distinct
phenotypes depending on environmental conditions. Adaptive phenotypic plasticity
leads to a better match between phenotype and selective environment
and can be a solution for dealing with fluctuating environments. Many insects
living in such environments have evolved phenotypic plasticity, including seasonal
polyphenisms in butterfly wing patterns. This study investigates the proximate
mechanisms (genetic and physiological) behind developmental plasticity in
butterfly wing patterns, and explores their potential role in contributing to how
species cope with changing environments.
We analysed the data on the effects on adult phenotypes (including wing patterns
and body-part allocations) of ecdysteroid manipulations in pupae, and
we started preparing two manuscripts where these results will be reported on
(Mateus et al. in prep; Oostra et al. in prep). We also finished gathering images
to characterize wing pattern reaction norms for different genetic backgrounds
(to assess genetic-by-environment effects, and the role of candidate loci in
plasticity).
EVOLUTION OF CASTE POLYPHENISM IN SOCIAL INSECTS:
PATTERNS OF MORPHOLOGICAL DIVERSIFICATION IN ANTS
Caste determination in ants is a classic example of developmental plasticity.
Larvae of the same genotype can develop into adults with very distinct morphologies,
each adapted for different roles within a colony. Typically, one or a
few larger and winged queens ensure the reproductive function, whereas many
wingless workers are responsible for colony maintenance. The developmental
switch into alternative phenotypes is regulated by larval nutrition, which itself
is under the control of the social environment. In collaboration with the group
of Christian Peeters in Paris, this project studies how plastic developmental systems
are regulated, and how they evolve and diversify. Specifically, we want to:
1. Establish a link between caste-specific morphologies and behaviours, in
relation to colony ecology;
2. Characterize the environmental regulation of caste development.
We analysed the data and started to prepare a manuscript (Keller et al. in prep)
on the characterisation of caste-specific morphologies and their correlations
with behaviour (at the level of caste-specific roles within a colony, and of reproductive
strategies of whole colonies) for multiple ant species. Roberto Keller
also established new lab populations of the ant Aphaenogaster senilis and
established “colony partition” protocols to manipulate frequency of different
sexes and castes produced.
MORPHOLOGICAL DIVERSIFICATION THROUGH THE EVOLUTION
OF DEVELOPMENTAL NETWORKS
The genes that regulate development are organized into intricate networks
whose origin and evolution remains a largely unresolved topic. Of great interest
is to what extent the different components of such networks contribute to
phenotypic variation and diversification. The evolutionary outcome of changes
on a developmental network depends on both the nature of the change and
the point in the network hierarchy where the change occurs. The diversified
eyespot patterns that decorate the wings of satyrine butterflies offer the opportunity
to address these issues. Analysis of cross-species diversity and within-species
variation in wing colour patterns can be integrated with an analysis
of the underlying sequence of developmental steps and genetic underpinnings.
Leila Shirai (PhD student) will investigate which type of changes in the underlying
gene networks and respective developmental mechanisms are responsible
for morphological diversification of this model novel trait.
We carried out the phylogenetic analysis of the recruitment of four conserved
genes for expression in association with the early establishment of eyespots and
eyespot-like elements in 13 species. The results of this analysis were prepared
IGC ANNUAL REPORT ‘11
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as a manuscript submitted in 2011 (Shirai et al. BMC Evol Biol 2012). Leila Shirai
has also started to explore a novel technique for the functional analysis of the
Wingless protein in the production of colour rings in pupal wings of two eyespot
lab models.
WOUND RESPONSE AND PIGMENTATION PATTERN FORMATION:
CELLULAR, MOLECULAR AND EVOLUTIONARY CONSIDERATIONS
The healing of damage to the epidermis is a vital and universal process which
involves pathways associated with scab formation, tissue repair and immunity.
Despite the evolutionary conservation of many aspects of wound response,
there is also much diversity in this process. An interesting example occurs
in Lepidopterans that can develop organized pigmentation patterns around
wound sites, which resemble native pattern elements called eyespots (an evolutionary
novelty). In this project, Maria Adelina Jerónimo (PhD student) will
use a butterfly lab model to study the molecular, cellular and genetic mechanisms
behind the formation of damage-induced patterns to gain new insights
both into wound response (healing of developing tissues and involvement of
melanin-pathway genes) and into the origin of evolutionary novelties (such as
butterfly eyespots).
This project started in May 2011 and Adelina Jerónimo has focused mostly on
preliminary data collection and data analysis to optimize experimental protocols
and to help guide experimental design.
IGC ANNUAL REPORT ‘11
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CELL CYCLE
REGULATION
Mónica Bettencourt-Dias Principal Investigator
PhD in Molecular Cell Biology, UCL, Univ. London, UK
Research Associate, University of Cambridge, UK
Principal Investigator at the IGC since 2006
link to external website
Our research focuses on cell cycle progression and the cytoskeleton in normal
development and disease. We are particularly interested in the role played by
microtubule organising structures, such as the centrosome, cilia and flagella.
Despite their importance, we know very little about centrosome and cilia biogenesis
or how they may go awry in human disease. Our laboratory combines
studies in model organisms with studies in human cells, bioinformatics and
mathematical modelling to have an integrated view of this process. An understanding
of the pathways involved in cell cycle and cytoskeleton can generate
diagnostic and prognostic markers and hopefully provide novel therapeutic targets
in human disease.
CONTROL OF CENTRIOLE STRUCTURE AND NUMBER
In this grant we are asking two fundamental questions that are central to human
disease: how is centriole structure and number established and regulated in
the eukaryotic cell? To address these questions we propose to identify new
molecular players, and to test the role of these and known players in the context
of specific mechanistic hypotheses, using in vitro and in vivo models. We
propose to develop novel assays for centriole structure and regulation in order
to address mechanistic problems not accessible with today’s assays. In our
search for novel components we will use a multidisciplinary approach combining
bioinformatics with high throughput screening. The use of in vitro systems will
allow the quantitative dissection of molecular mechanisms, while the study of
those mechanisms in Drosophila will allow us to understand them at the whole
organism level.
GROUP MEMBERS
Adan Guerrero (Post-doc; started November 2011)
Daniela Brito (Post-doc)
Mariana Faria (Post-doc)
Susana Gouveia (Post-doc)
Swadhin Jana (Post-doc; started in June 2011)
Filipe Leal (PhD student)
Inês Bento (PhD student)
Inês Ferreira (PhD student)
Zita Carvalho Santos (PhD student)
Pedro Machado (Technician)
Tiago Amado (Technician)
COLLABORATORS
Eric Karsenti (EMBL, Germany)
David Glover (University of Cambridge, UK)
Michel Bornens (Institut Curie, France)
Keith Gull (University of Oxford, UK)
Juliette Azimzadeh (University of California at San Francisco, USA)
José Pereira-Leal (IGC, Portugal)
Miguel Godinho Ferreira (IGC, Portugal)
Brian Tsou (Sloan Kettering Institute, USA)
Max Loda (Harvard Medical School, USA)
Paula Chaves (Instituto Português de Oncologia, Portugal)
FUNDING
European Molecular Biology Organisation (EMBO), UK
Fundação para a Ciência e a Tecnologia (FCT), Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Speed-dating at Optimus Alive! Music Festival, July
During this year we have been developing tools to follow PLK4 levels and activity
through the cell cycle. Moreover we have been developing assays to follow
centriole biogenesis in vitro. The laboratory will spend some time in the Marine
Biology Laboratory to further develop those assays.
CAUSES AND CONSEQUENCES OF CENTROSOME AND PLOIDY ABNORMALITIES
IN HUMAN CANCER USING BARRETT'S OESOPHAGUS AS A MODEL
Centrosomes are the major microtubule-organising centres in animal cells and
abnormalities in these structures have been observed in cancer. Indeed, compelling
data has shown that cells from many cancers have multiple and abnormal
centrosomes that are either correlated with tumour malignancy or considered
an early event during tumorigenesis. However, to this date, a causative link
between centrosome abnormalities, which can be classified as numerical (e.g.
extra centrosomes) or structural (e.g. longer centrioles), and cancer remains elusive.
Our aim is to investigate how centrosome abnormalities contribute to tumorigenesis
using Barrett's oesophagus (BE), a premalignant condition and only
known precursor of oesophageal adenocarcinoma, as a model for human cancer.
Our initial studies revealed that BE contain cells with abnormal centriolar structure
but fewer cells contain centrosome amplification. Therefore, we decided to
extend our work to breast cancer since in this case centrosome amplification is
well characterised.
REGULATION OF CILIA BIOGENESIS IN DEVELOPMENT AND HUMAN DISEASE
The first described intermediate in centriole assembly showing nine-fold symmetry
is a structure called cartwheel. Bld10/CEP135 and SAS-6 are two components
of the cartwheel. We have recently found that Bld10 is likely to play a
role in the assembly of the transition zone of Drosophila sperm (A1). Mutants in
Bld10 show axonemes that lack the central microtubule pair, are immotile, and
males are sterile. We are exploring these parallels, in particular by studying the
function, regulation and interaction partners of SAS6 and BLD10 in centriole
and axoneme formation. Drosophila testes are particularly useful to tackle this
question as centrioles/basal bodies are particularly long and easy to image.
Electron microscopy of sperm tails.
IGC ANNUAL REPORT ‘11
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We have found a new precursor structure of the central microtubule pair in
spermatocyte primary cilia. These structures are missing in Bld10 mutants. We
have characterised the role of BLD10 in microtubule stabilisation and assembly
of the central microtubule pair of the axoneme.
REGULATION OF CENTRIOLE NUMBER IN DEVELOPMENT
Oocytes are devoid of centrioles. Fertilisation brings the basal body necessary
to form the sperm tail, which becomes the first centriole of the zygote. The
disappearance of centrioles during oogenesis and the inhibition of de novo
formation might be central in avoiding parthenogenesis. We are now describing
the regulation of centrosome proteins in the female germline in order to get
insights into the factors that regulate centriole disappearance and that prevent
de novo formation.
We are completing the description of the cascade of events during oogenesis,
which correlates with centriole loss. We are testing hypotheses regarding how
centriole loss is regulated.
MICROTUBULE REGULATION IN CENTRIOLE BIOGENESIS MECHANISMS
Studies on microtubules (MTs) have originated a vast amount of consistent data
to substantiate their functional mechanisms. Yet, it is quite paradoxical that
while these polymers are recognised to be the major component of centrioles,
little is known about their regulation in centriole biogenesis. This may stem
from the fact that many microtubule regulators (MTRs) have pleiotropic roles.
Our own data and that of other groups suggest that both known MTRs and
centriole specific proteins play an important role in the recruitment of centriole
components and in the assembly and elongation of centriole MTs. We propose
to take advantage of that knowledge to gain further insight on centriole biogenesis.
We will use a highly multidisciplinary approach. We will investigate the function
of two MTRs that we found to play a role in centriole biogenesis. In parallel, we
will acquire a broader picture of this process, by identifying novel MTRs with a
role in centriole initiation and elongation.
We are completing the description of the cascade of events during oogenesis,
which correlates with centriole loss. We are testing hypotheses regarding how
centriole loss is regulated.
MICROTUBULE REGULATION IN CENTRIOLE BIOGENESIS MECHANISMS
Studies on microtubules (MTs) have originated a vast amount of consistent data
to substantiate their functional mechanisms. Yet, it is quite paradoxical that
while these polymers are recognized to be the major component of centrioles,
little is known about their regulation in centriole biogenesis. This may stem
from the fact that many microtubule regulators (MTRs) have pleiotropic roles.
Our own data and that of other groups suggest that both known MTRs and
centriole specific proteins play an important role in the recruitment of centriole
components and in the assembly and elongation of centriole MTs. We propose
to take advantage of that knowledge to gain further insight on centriole biogenesis.
We will use a highly multidisciplinary approach. We will investigate the function
of two MTRs that we found to play a role in centriole biogenesis. In parallel, we
will acquire a broader picture of this process, by identifying novel MTRs with
a role in centriole initiation and elongation. This grant will be focused on the
screen, which we will perform in-house. In task 1 we propose to build a list of
candidates to screen for players in centriole elongation.
We designed two assays to uncover players in the different phases of the centrosome
cycle: centriole duplication and centriole elongation. We are now finishing
the characterisation of the best centriole markers to finally start the
screen.
Drosophila sperm tails stained with centriole marker (red), tubulin (green) and DNA.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
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QUANTITATIVE
ORGANISM BIOLOGY
Jorge Carneiro Principal Investigator
PhD in Biomedicine, Universidade do Porto, 1997
Post-doctoral Fellow, Theoretical Biology and Bioinformatics,
University of Utrecht, NL
Coordinator of the Estudos Avançados de Oeiras
Director PhD Programme in Computational Biology
Principal Investigator at the IGC since 1998
link to external website
We are broadly interested in the mechanisms underlying organismal properties
(namely immunological tolerance, body form and sensorimotor coordination)
and in creating quantitative modelling frameworks that bridge between the biochemical
micro-dynamics of individual cells and the supracellular collective behaviour.
In immunology, we study the cell population dynamics and homeostasis
involved in the interplay between health, autoimmunity and cancer; and search
for methods to measure repertoire diversity and structure. In cell biology, we
study stochastic gene expression and epigenetic regulation focusing on several
instances of monoallelic gene expression (e.g. antigen-receptor and cytokine
genes). We are also interested in understanding cellular form and motility, and
collective tissue dynamics. We are creating new simulation methods and tools
for rigorous comparison of simulation results with live-imaging data.
BIOINSTBOTS:
FROM BIO-INSPIRED TO INSTITUTIONAL-INSPIRED COLLECTIVE ROBOTICS
The main inspiration for collective robotics modelling, analysis and design originated
from the biology of social insects. Despite the success of swarm robotics
in relatively simple applications, there is no systematic method to design individual
behaviours at the micro level, including their interaction-based actions,
in order to obtain a desired collective behaviour at the macro level. In fact,
the emergent nature of the collective behaviour is a principle that precludes
goal- or performance-oriented design. We seek to study and formalise laws
that govern collective systems with the aim of synthesising systems of relatively
simple robots that display complex behaviour. In order to achieve this goal,
we study both biological systems and social systems. From biology, we focus
on cell populations. A single cell is relatively simple when compared with a cell
population, a cellular tissue or an organism. While from sociology, we focus on
institutional economics. Our objective is to bring together theories, ideas and
inspiration from institutional economics and cell biology under a common formal
framework for large robot populations modelling and analysis.
GROUP MEMBERS
Danesh Tarapore (Post-doc)
Thiago Guzella (PhD student) (co-supervised by Vasco Barreto))
Tiago Macedo (PhD student)
Tom Weber (PhD student)
Pedro Silva (Masters student) (left in September)
COLLABORATORS
Alberto Darszon (Instituto de Biotecnologia, UNAM, Cuernavaca, Mexico)
Gabriel Corkidi (Instituto de Biotecnologia, UNAM, Cuernavaca, Mexico)
Michal Or-Guil (Research Center ImmunoSciences (RCIS),
Humboldt University, Berlin, Germany)
Carmen Molina-Paris and Grant Lythe (Department of Mathematics.
University of Leeds, UK)
Pedro Lima (Institute of Systems and Robotics. IST/UTL, Portugal)
Anders Lyhne Christensen (Instituto de Telecomunicações
& Instituto Universitário de Lisboa (ISCTE-IUL), Portugal)
FUNDING
Fundação para a Ciência e a Tecnologia, (FCT), Portugal
Conacyt - Consejo Nacional de Ciencia y Tecnología, Mexico
For detailed quantitative simulations of cell populations and tissues that can be
rigorously formalised and validated by comparison with the natural system, we
focused on two cases studies:
1. CD4 T cell population dynamics;
2. Spatial pattern formation and dynamics in cell aggregates and tissues.
We redeployed T cells dynamics within a multiagent robotic system showing
that the collective dynamics brings forth a classification of environmental objects
according to some proto “self-nonself” categorisation that was not prescribed
to the individual agents.
MORPHODYNAMIC MODELLING AND IMAGING OF SEA URCHIN SPERMATOZOA
SWIMMING AND CHEMOTAXIS
Flagella and cilia are structurally conserved, present in many cell types and are
fundamental for many biological processes. Multiple diseases, including disruption
of left-right body asymmetry, result from ciliar protein mutations. Flagellar
driven sperm motility is crucial for gamete encounter and fertilisation. The objective
of this collaborative project with the group of Alberto Darszon from the
Institute for Biotechnology, UNAM (Cuernavaca, Mexico) is to gain insight into
sea urchin spermatozoa flagellar morphodynamics, making use of state of the
art imaging techniques and mathematical modelling. We search to understand
how molecular signals produced by the egg regulate intracellular [Ca2+] and flagellar
beating to guide spermatozoon towards the egg in the 3D world. We aim
to develop morphodynamical models of sperm cells and deploy these models
for quantitative image analysis.
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We have previously developed a spermatozoon model that integrates the molecular
signalling networks, the flagellum morphodynamics, and the swimming
behaviour in presence or absence of environmental cues. This model semiquantitatively
describes the trajectories of chemotatic and non-chemotatic
spermatozoa of L pictus and S purpuratus, respectively. After calibrating the
morphodynamical model using high temporal timelapse imaging of L pictus
sperm we used the model to successfully track S purpuratus spermatozoa
[Pedro Silva's Masters thesis, 2011].
A
B
C
INTEGRATED MORPHODYNAMICAL MODEL OF A CHEMOTACTIC SEA URCHIN
SPERMATOZOON.
A - signal transduction network controlling intracellular [Ca2 + ] and flagellar beating
pattern. B - observed (left) and modelled (right) time course of intracellular
[Ca2 + ]-spike trains observed in single cells following the response to sperm activating
peptide (SAP). C - observed (blue graph) and modelled (red graph) chemotactic
trajectory of spermatozoon in response to SAP gradient.
IGC ANNUAL REPORT ‘11
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MOLECULAR
NEUROBIOLOGY
Diogo S. Castro Principal Investigator
PhD in Cell and Molecular Biology, Karolinska Institute, 2001
Post doctoral fellow, MRC National Institute for Medical Research, London, UK
Senior Investigator Scientist, MRC National Institute for Medical Research, London, UK
Principal Investigator at the IGC since 2010
The assembly of a functional nervous system depends on the coordinated
generation of neurons and glia cells from multipotent neural stem cells in the
developing embryo. The progression of this differentiation process is associated
and controlled by changes in gene expression programmes that need to
be very tightly regulated. For the moment we are mostly interested in understanding
the role played by various transcription factors, with a special focus
on bHLH proneural proteins, in neurogenesis. We aim at characterising their
transcriptional networks, as well as understanding the molecular mechanisms by
which such programmes are regulated, and how they contribute to the acquisition
of specific cellular phenotypes. In our work we take advantage of recently
developed genomic approaches that allow the characterisation of transcriptional
programmes at a genome wide level, complemented with more classical
methods to study gene expression, having the mouse embryo as a model
system.
GROUP MEMBERS
Alexandre Raposo (Post-doc, started in August 2011)
Vera Teixeira (Post-doc, started in May 2011)
Francisca Vasconcelos (PhD student)
Pedro Rosmaninho (PhD student, started in April 2011)
COLLABORATORS
François Guillemot (MRC National Institute for Medical Research, London, UK)
Stefan Momma (Johann Wolfgang Goethe University, Frankfurt, Germany)
Deolinda Lima (Faculdade de Medicina da Universidade do Porto,Portugal)
Vania Broccoli (San Raffaele Scientific Institute, Milan, Italy)
Carlos Parras (Hôpital de la Pitié-Salpêtrière, Paris, France)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Instituto Gulbenkian de Ciência (IGC), Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Biology in Modern Times seminars for teachers, IGC, April
TRANSCRIPTIONAL CONTROL OF VERTEBRATE NEUROGENESIS
BY THE PRONEURAL FACTOR MASH1
Vertebrate neurogenesis is controlled, to a large extent, by basic helix-loophelix
proneural factors such as Mash1 (aka Ascl1). The use of Mash1 in reprogramming
protocols aiming at generating mature neurons from other cell types
stresses the importance of understanding the molecular mechanisms that underlie
its activity. Recently, we have performed the first genome wide characterisation
of a neurogenic programme downstream of Mash1, by the large
scale identification of its transcriptional targets. Strikingly, our results showed
that Mash1 directly controls both early (eg. cell fate commitment) and late (eg.
neurite outgrowth) steps of neurogenesis. This project aims at investigating
the epigenetic and transcriptional mechanisms that contribute to the temporal
regulation of neurogenesis by Mash1, by analysing the role played by the
chromatin landscape and interactions with other transcriptional networks that
operate in neural progenitors.
We have identified the zinc-finger transcription factor Myt1 as a direct target of
Mash1 in a neurogenic context. A transcriptional synergy between the two factors
in promoting differentiation suggests they may define an important feedforward-loop
at the onset of neurogenesis. The genome-wide characterisation
of Myt1 binding events in neural progenitors predict functional interactions with
other important transcriptional regulators, currently being investigated.
THE TRANSCRIPTIONAL NETWORK OF THE ZINC-FINGER FACTOR ZEB1
AND ITS FUNCTION IN NEURAL STEM/PROGENITOR CELLS
Current interest in neural stem cells derives from the prospect of using them
in brain repair strategies, but also to understand neurodevelopmental pathologies.
This will require, however, a significant improvement of our understanding
of the gene expression programmes associated with their maintenance and differentiation,
and how these are regulated. Recently, several lines of evidence
suggest a regulatory function for the zinc-finger transcription factor ZEB1, both
in embryonic neural stem/progenitor cells, and in human tumours of neural
origin. Here we propose to use a multidisciplinary approach, combining mouse
genetics and genomics, to characterise the function of ZEB1 in neural development.
Moreover, a comparison of the ZEB1 transcriptional programmes in human
foetal- and glioma-derived stem cells will be carried out, providing important
insights into ZEB1 function in tumour initiation and development.
We have begun to characterise the transcriptional programme downstream of
Zeb1 in neural stem/progenitor cells, having performed its genome-wide location
analysis, by chromatin immunoprecipitation followed by deep sequencing
(ChIP-seq).
HES6 PROMOTER.
Genome-wide location analysis by ChIP-seq shows binding of the transcription
factors Mash1, Hes1 and Myt1 to the proximal promoter region of the neurogenic
gene Hes6.
IGC ANNUAL REPORT ‘11
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POPULATION
AND CONSERVATION
GENETICS
Lounès Chikhi Principal Investigator
PhD in Population Genetics, Pierre et Marie Curie (Paris VI), 1995
Chargé de Recherche 1ère classe CNRS (Centre National de la Recherche Scientifique)
Principal Investigator at the IGC since 2007
link to external website
The Population and Conservation Genetics Group (PCG) carry out research in
the area of conservation and human population genetics. Genetic data can be
used to reconstruct the recent demographic history of populations and species
to identify key features of that history such as contractions and expansions.
We are interested in understanding the statistical properties of genetic data
in wild or managed populations to determine when and how genetic data can
be used to make statements about populations’ recent evolutionary history.
We are also working on the conservation of rare and endangered species providing
estimates of the numbers of remaining lemurs in the north and northwest
of Madagascar. Our work involves field and lab work together with data analysis,
computer simulations, and the development of simulation tools.
DEMOGRAPHIC AND GENETIC RESPONSES TO HABITAT FRAGMENTATION
AND HABITAT LOSS IN TWO LARGE FOREST MAMMALS
Habitat loss and habitat fragmentation are among the major causes of biodiversity
loss affecting tropical forests across the world. The project fosuses on
two endangered species from Borneo whose environment has undergone intensive
deforestation in the last 100-150 years. The Bornean Asian forest elephant
(Elephas maximus borneensis) and the Bornean orang-utan (Pongo pygmaeus)
are among the most endangered species living in Sabah (North Borneo), and are
affected by the increasing conversion of forest into oil-palm plantations. While
genetic data are accumulating on African great apes and elephants, the data
on their Asian relatives are very few and mostly based on captive populations.
There is a need for comparative data (across species and habitats), and for
conceptual and theoretical tools. The project aims at using population genetics
modelling and genomic data from non-invasive samples to analyse the patterns
of genetic diversity within and between populations.
The genomic markers identified using NGS techniques have been tested and typed
on DNA extracted from blood and faecal material. Very limited genetic diversity
across microsatellites and SNPs was identified this way. Altogether eight papers
were published (three in 2009, four in 2010 and one in 2012), including two in Genetics,
one in Molecular Ecology, one in Heredity, and two in Mol. Ecol. Resources.
Three are currently being written. We thus expect 11 papers for this project.
GROUP MEMBERS
Cécile Vanpé (Post-doc)
Reeta Sharma (Post-doc)
Bárbara Parreira (PhD student)
Isabel Alves (PhD student, started in May)
João Alves (PhD student)
Jordi Salmona (PhD student)
Rita Rasteiro (PhD student, left in September)
Isa Pais (Research Assistant)
Célia Rodrigues (Trainee & Optimus Alive Research Fellow)
Sam Viana (Optimus Alive Research Fellow, left in March)
COLLABORATORS
Benoît Goossens (School of Biosciences, Cardiff University, UK & Danau
Girang Field Center - Sabah Wildlife department, Malaysia)
Nurzhafarina Othman (Universiti Malaysia Sabah, Kota Kinabalu, Malaysia)
Michael Bruford (School of Biosciences, Cardiff University, UK)
Marc Ancrenaz (Kinabatangan Orang-utan Conservation Project, Sukau,
Sabah, Malaysia)
Isabelle Lackman-Ancrenaz (Kinabatangan Orang-utan Conservation Project,
Sukau, Sabah, Malaysia)
Brigitte Crouau-Roy (Univ. de Toulouse, France)
Christophe Thébaud (Univ. de Toulouse, France)
Clément Rabarivola (Univ. Mahajanga, Madagascar)
Brigitte Crouau-Roy (Univ. de Toulouse, France)
Christophe Thébaud (Univ. de Toulouse, France)
Clément Rabarivola (Univ. Mahajanga, Madagascar)
Ute Radespiel (Institute of Zoology, Univ. of Veterinary Medicine Hannover,
Germany)
Mark Beaumont (University of Bristol, UK)
Mathias Currat (Department of Anthropology and Ecology, University
of Geneva, Switzerland)
Juan Montoya-Burgos (University of Geneva, Switzerland)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Fondation pour la Recherche sur la Biodiversité, France
PUBLIC ENGAGEMENT IN SCIENCE
Talks for school students, Porto (May)
Optimus Alive! Biodiversity Activity, Algés (July)
GENETIC EFFECTS OF HABITAT LOSS AND FRAGMENTATION:
COMPARATIVE ANALYSIS OF SEVERAL LEMUR SPECIES
IN TWO NEIGHBOURING REGIONS OF MADAGASCAR - I
Madagascar is well known for its extremely diverse and mostly endemic fauna and
flora. However, the island has suffered from drastic environmental changes in last
millennia, leading to the extinction of many species. Lemurs are forest-dwelling
animals and are thus particularly affected by these changes. The relative importance
of natural and anthropogenic factors in the extinction of populations and
species is likely to have varied from one region to another and from a group of
species to another. However, the consequences of these disturbances on the
genetic structure of fragmented populations have not been studied for many
species and are still poorly understood. Our aim in this project is to carry out
the first comparative analyses across several lemurs genera and study the effect
of habitat loss and fragmentation in the north and northwest of Madagascar,
and to develop new genetic markers for this aim.
Non-invasive material has been collected and densities have been estimated for
several Propithecus species increasing the regional sampling that had been initiated
in the previous years. Papers have been published on both the genetic and density
estimation work. Sampling of the Eulemur species has proven more difficult and
sample sizes for wild animals are still limited. Altogether eleven papers were published
(in Proc. Roy Soc. B, BMC Evol. Biol., Biol. Cons., Am J Prim, Mol Ecol, Genetics.)
IGC ANNUAL REPORT ‘11
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GENETIC EFFECTS OF HABITAT LOSS AND FRAGMENTATION:
COMPARATIVE ANALYSIS OF SEVERAL LEMUR SPECIES
IN TWO NEIGHBOURING REGIONS OF MADAGASCAR – II
The island of Madagascar is one of the most important biodiversity hot spots
in the world with extremely high levels of endemism in primates, amphibians,
reptiles, and plants. Lemurs, with around 100 species represent one of the most
spectacular adaptive radiation. However, landscapes are now reduced to a mosaic
of fragmented forests. Despite this alarming situation, most genetic studies
focus on the identification of new species, or on the diversity within one or two
populations, and analyse one species in one geographical area. In this project
our aim is to:
1. Study HL&F across lemur taxa in two neighbouring regions;
2. Develop inferential methods that explicitly model and account for the past
demographic history of populations and species;
3. Develop genomic markers to answer these questions.
Population sizes and densities have been estimated in the field for nocturnal
(Microcebus and Lepilemur genera) and dirunal (Propithecus) lemurs. Microcebus
and Lepilemur have been captured and biopsies collected for both genera.
Five papers were published, including one on the density of Microcebus and
Lepilemur, and one on Propithecus coronatus, and some theoretical papers on
spatial processes. Three manuscripts have been submitted.
IGC ANNUAL REPORT ‘11
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32

NEUROBIOLOGY
OF ACTION
Rui M. Costa Principal Investigator
PhD in Biomedical Sciences, Universidade do Porto, Portugal, 2002
Section Chief, NIH, USA
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Member of IGC Ethics Committee
Principal Investigator at the IGC since 2009
link to external website
To study actions is to study the way we do things, which is different than studying
how we remember stimuli, or facts and events. Some actions are innate or
prewired. Others are learned anew throughout life, likely through a process of
trial and feedback. We currently focus on understanding the processes mediating
the latter.
Our overall goal is to understand how changes in molecular networks in the
brain modify neural circuits to allow the generation of novel actions and their
shaping by experience. To achieve this, we subdivided our experiments into different
sub-goals to study action generation, action shaping and automatisation
and action goals.
NEURAL MECHANISMS OF SKILL AND SEQUENCE LEARNING
Understanding how novel actions are learned and consolidated as sequences
of movements and skills are the main aims of this project. We have uncovered
neural activity in basal ganglial circuits that are related to the learning and execution
of sequences of movements. We also used optogenetics to identify and
manipulate the neurons mediating this activity.
CORTICOSTRIATAL MECHANISMS UNDERLYING GOAL-DIRECTED
ACTIONS AND HABITS
Our goal is understanding the difference in the brain between intentional actions
and habits or routines. We have uncovered that the dopamine transporter is a
critical gate for habit formations; and also that different corticostriatal circuits
dynamically interact during the shift between goal-directed actions and habits.
GROUP MEMBERS
Catherine French (Post-doc)
Cristina Afonso (Post-doc)
Fatuel Aguilar (Post-doc)
Gabriela Martins (Post-doc)
Rodrigo Oliveira (Post-doc, started in April)
Vitor Paixão (Post-doc)
Albino Maia (Clinical Research Fellow)
Rosalina Fonseca (Clinical Research Fellow)
Ana Mafalda Vicente (PhD student)
Eduardo Ferreira (PhD student)
Fernando Santos (PhD student)
Ana Maria Vaz (Research Technician)
COLLABORATORS
Jose Carmena (UC Berkeley, USA)
FUNDING
European Research Council (ERC), European Commission;
FP7 Marie Curie Integration grant, European Commission
Champalimaud Foundation, Portugal
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Contract research, EcBio, Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Brain Awareness week, Lisbon area, March
Visits to schools, Lisbon and Guarda
NEURAL MECHANISMS UNDERLYING THE GENERATION OF NOVEL ACTIONS
This project aims to understand how new self-initiated actions are generated
and how this ability is hampered in Parkinson´s disease. We have developed a
new methodology to classify in an unbiased manner different behavioural and
neural states.
SPECIFICITY OF CRE EXPRESSION IN in PV Cre AND ChAT Cre MICE.
A - Montage of images from an adult brain section through the striatum demonstrating
YFP colocalisation with PV in the PV Cre mouse line crossed with a ROSA26-
YFP reporter mouse. B-G - The inset in dorso-lateral striatum depicts the location
from where the smaller images were obtained. B-D - The first column demonstrates
PV immuno-reactivity (in red; B), YFP expression (green; C), and colocalisation
of both (yellow; D) in the PV Cre -ROSA-YFP mouse striatum. E-G - The second
panel shows ChAT immuno-reactivity (in red; E), YFP expression (green, F), and
colocalisation of both (yellow; G) in a ChAT Cre -ROSA-YFP mouse striatum. Scale
bars = (A) 500µm; (D) 125µm for (B-G). (by Gabriela Martins)
THE ROLE OF DIFFERENT STRIATAL CIRCUITS IN ACTION LEARNING.
Left - Mice performing a behaviour task-walking on a rotating rod-which requires
action learning that depends on striatal circuits in the brain. Right - Identification
of striatal medium spiny neurons of the direct pathway expressing D1 dopamine
receptor (in red) and striatal medium spiny neurons of the indirect pathway expressing
D2 receptor (in green). Note the two populations do not overlap.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
33

LYMPHOCYTE
PHYSIOLOGY
Jocelyne Demengeot Principal Investigator
PhD in Cellular and Molecular Biology, Université AIX-MARSEILLE II, 1989
Post-doctoral Fellow, Columbia University, NY, USA
HHMI Research Associate - Harvard Medical School, Boston, USA
Research Associate, Institut Pasteur, Paris, France
Deputy Director for Scientific Affairs
Scientific supervisor of the Antibody production facility
Head of the Animal House facility
Principal Investigator at the IGC since 1998
We are concerned with those properties of the immune system that guarantee
tissue integrity as well as tolerance to commensals and food antigens while
maintaining the ability to mount efficient responses to infectious agents. We
approach the cellular and molecular bases of immune regulation through the
analysis of various mouse models, notably of spontaneous or induced autoimmune
and immuno-pathological inflammation. Keeping in mind that the vertebrate
immune system relies on the production of a very large diversity of
antigen receptors through genomic rearrangement by the RAG recombinases,
we also maintain a line of research assessing the consequences of deregulated
RAG activity on genomic integrity and on lymphocyte homeostasis. Our
interests merge within various collaborative projects, notably addressing the
efficiency of immunotherapies for Systemic Lupus Erythematosus, Rheumatoid-
Arthritis and Type-1 Diabetes.
GROUP MEMBERS
Andreia Lino (Post-doc)
Elodie Mohr (Post-doc)
Marie Bonnet (Post-doc)
Marie Louise Bergman (Post-doc)
Ricardo Paiva (PhD student)
Sandra Gama Garcies (PhD student, left in October)
Aleksandra Gumienny (Technician, started in October)
Ana Paula Regalado (Technician, started in November)
Catarina Martins (Technician)
Maria Espírito Santos (Technician, left in June)
Rosa Maria Santos (Technician, left in November)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Framework Programme 7, European Commission
RAG MEDIATED DNA REARRANGEMENT
The adaptive immune system of the jawed vertebrates emerged about 500
million years ago involving, as a major novelty, the somatic generation of an
extremely large diversity of antigen receptors by a mechanism of site specific
DNA recombination. The Rags introduce DNA breaks at specific sequences -
named Recombination Signal Sequences (RSS) found at the border of a large set
of gene segments. RSS are composed of either 28 or 39 nucleotides, only a few
of which are conserved. Given this degeneracy, RSS-like sequences can be identified
outside the antigen receptor loci. Such “cryptic-RSS” (cRSS) have been occasionally
tested, shown to support Rag mediated recombination and involved
in the emergence of some lymphoid tumours. With the aim to formally establish
the frequency, efficiency and nature of cRSS in the genome, we joined with five
other groups at IGC to combine experimental, bio-informatic and mathematical
approaches to perform unbiased large-scale analyses.
To calibrate a novel model identifying RAG targets, we experimentally scored
60 RSS pairs using our new fluorescence based reporter of Rag activity. We also
classified epigenetic markers and defined the genetic repertoire in differentiating
lymphocytes, at the corresponding V locus. In parallel, we confirmed that our
novel transgenic mouse model, where Rag activity can be induced upon oral administration
of tamoxiphen, is amenable to test the effect of Rag activity in vivo.
IMMUNE REGULATION
A subset of T cells, expressing the transcription factor Foxp3, dampens immune
responses in an antigen specific manner. These cells are first selected in the
thymus through interaction with an MHC-peptide expressed locally and therefore
encompass a TCR repertoire enriched in self-reactivities. Yet, a wide array
of molecules produced by commensals, brought in by food or expressed by the
foetuses is also tolerated by the immune system. This paradox calls for a formal
evaluation of the rules governing Treg differentiation, their maintenance and
expansion as well as their domain of competences. Our specific aims are:
1. To establish the origin of the antigens that drive regulatory T cells;
2. To establish the origin of regulatory T cell specific to strictly peripheral
antigens;
3. Along with the hygiene theory, to test the role of the microbiota in modulating
immune tolerance;
4. To asses the role of B cells and B cell products in the control of T cell
homeostasis.
CONFOCAL MICROSCOPY IMAGES OF SPLEEN SECTIONS REVEALING A SPECIFIC
ROLE FOR SECRETED IMMUNOGLOBULIN M (IGM) IN THE CONTROL OF MARGINAL
ZONE (MZ) B CELLS NUMBER.
Arrowheads indicate the MZ B cells (IgM+, blue) at the periphery of the periarteriolar
lymphatic sheaths formed by the T zone (CD3e+, green) and the follicles
(IgM+IgD+, pink). A) wild-type mice. B) AID-/- mutant that produces IgM but no
other immunoglobulins. C) µS-/- mutant that cannot secrete IgM but produces
other immunoglobulins.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
34

During this year we demonstrated that:
• Thymic epithelial cells present and cross-present antigens to drive Treg
differentiation.
• Pregnancy associates with the de novo differentiation of foetus specific
Foxp3+ cells, necessary for the mother's survival.
• Recent thymic emigrants are the precursors of Treg differentiated in the
periphery.
• B cells and immunoglobulins control lymphocytes homeostasis (see picture).
IMMUNOTHERAPIES
The use of specific monoclonal antibodies, a class of "biologicals" in the treatment
of autoimmune patients has provided spectacular clinical results. However
a large fraction of patients develop an immune response against the drug and
produce antibodies, thus subverting the benefit of the therapy. We aimed at
conducting a pilot study to assess the relevance of drug immunogenicity in
clinical practice in Portugal.
We implemented ELISA assays to measure anti-drug antibody levels and drug
level in sera. We monitored 30 patients treated with neutralizing anti-TNF antibodies.
A retrospective analysis of the clinical data and their correlation with
the ELISA data reveal that routine monitoring is highly advisable for the proper
management of patients and for economic concerns.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
35

PLANT
MOLECULAR BIOLOGY
Paula Duque Principal Investigator
PhD in Physiology and Biochemistry, Universidade de Lisboa, 1998
Postdoctoral Fellow, The Rockefeller University, New York, USA
Postdoctoral Associate, The Rockefeller University, New York, USA
Adjunct Assistant Professor, Queens College, City University of New York, USA
Principal Investigator at the IGC since 2006
The Plant Molecular Biology group uses Arabidopsis thaliana as a model system
to investigate how plants perceive and respond to environmental signals and
endogenous developmental cues at the molecular level. In particular, we focus
on the role of pre-mRNA splicing in the regulation of gene expression. The versatility
of this mode of regulation suggests that it is likely to play an important
contribution in ensuring the developmental plasticity and stress tolerance that
are essential for plant survival. Another major line of work in the lab is examining
the role of Major Facilitator Superfamily membrane transporters in plant
tolerance to abiotic stresses.
THE FUNCTIONAL SIGNIFICANCE OF ALTERNATIVE SPLICING IN ARABIDOPSIS
Alternative splicing is a key post-transcriptional mechanism for expanding proteomic
diversity and regulating gene expression in higher eukaryotes, with its
prevalence in many genomes pointing to crucial roles in biological processes.
In plants, stress-associated genes are particularly prone to alternative splicing,
which is also markedly affected by a wide variety of abiotic stresses.
In support of a functional role for alternative splicing in plant stress responses,
SR proteins, which are widely recognised as the major modulators of alternative
splicing, are stress-regulated at the transcriptional, post-transciptional and
translational levels in plants, indicating that these splicing factors may act as
central coordinators of responses to environmental changes. This project aims
at investigating the potential in vivo stress roles of plant-specific SR proteins.
GROUP MEMBERS
Estelle Remy (Post-doc)
Raquel Carvalho (PhD Student)
Sofia Carvalho (PhD Student)
Rita Batista (Trainee, left in August)
Carolina Feijão (Trainee, started in December)
COLLABORATORS
Ji He (The Samuel Roberts Noble Foundation, USA)
John Brown (The James Hutton Institute, UK)
Anthony Kinney (Dupont, USA)
Elena Baena-González (IGC, Portugal)
Isabel Sá-Correia (Instituto Superior Técnico, Portugal)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Public Talk, Centro Ciência Viva de Bragança, Portugal, June
Functional analysis of two Arabidopsis SR genes has revealed roles in the regulation
of sugar signalling and osmotic/salt stress responses during the early
stages of plant development, via modulation of the abscisic acid (ABA) stress
signalling pathway. The identification of endogenous targets of these splicing
factors is uncovering the first mechanistic links between SR protein function
and plant stress tolerance. We have started preparing two manuscripts reporting
these findings.
ROLE OF PLANT MAJOR FACILITATOR SUPERFAMILY TRANSPORTERS
IN ABIOTIC STRESS TOLERANCE
One way by which a living cell can achieve multiple drug resistance (MDR) is
by actively extruding toxic compounds via membrane pumps that catalyse
the efflux of a broad range of chemically distinct substrates. In Saccharomyces
cerevisiae, TPO1, a plasma membrane MDR transporter belonging to the
Major Facilitator Superfamily (MFS), determines the resistance to one of the
most widely used herbicides worldwide, 2,4-dichlorophenoxyacetic acid (2,4-D)
and to other xenobiotic compounds, presumably via active direct extrusion
from the yeast cell. Based on the role played by this MFS transporter in yeast
adaptation to toxic compounds, and in view of the substantial conservation of
molecular pathways among eukaryotic organisms, we are collaborating with the
Instituto de Biotecnologia e Bioengenharia at Instituto Superior Técnico with
the main goal of evaluating the role played by Arabidopsis thaliana MFS transporters
in 2,4-D resistance in particular and MDR in general.
The Arabidopsis sr45-1 mutant is hypersensitive to glucose during early seedling
development.
Using reverse genetics, we have found that three Arabidopsis MFS genes encoding
transporters sharing homology with the yeast TPO1 positively regulate
different aspects of abiotic stress response in plants, such as drought tolerance
(Remy et al., submitted) phosphate uptake during phosphorus starvation (Remy
et al., submitted) and resistance to elevated zinc levels in the soil (Remy et al.,
in prep.).
The ZIF2 MFS transporter conferring zinc resistance is specifically expressed in the
cortex and endodermis of the Arabidopsis root.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
36

CELL
BIOPHYSICS
AND DEVELOPMENT
José A. Feijó Principal Investigator
PhD in Cell Biology, Universidade de Lisboa, 1995
Full Professor, University of Lisbon, Portugal
Head of Cell Imaging & Ion Dynamics Facilities
Principal Investigator at the IGC since 2005
Research in our group is focused on developing integrated models of cellular
growth and morphogenesis using the pollen tube as a biological model, ion
dynamics as an experimental paradigm and theoretical modeling as an integrative
tool.
We have characterised novel ion channels essential for the pollen tube, by
means of imaging, electrophysiology, genetics and molecular biology. Furthermore,
we contributed to or deciphered some of the genetic and cellular mechanisms
behind pollen tube guidance and fertilisation in plants. Our group has
provided novel insights into the transcriptional status of plant male gametes
and its consequences for plant reproduction and improvement.
The members of the group were involved in imaging, transcriptomics and vibrating
probe electrophysiology services of the IGC.
ELECTROPHYSIOLOGICAL CHARACTERISATION OF MEMBRANE TRANSPORTERS
IN Arabidopsis thaliana POLLEN TUBE
In this project we are carrying out patch-clamp characterisation of chloridechannels
in pollen protoplasts, as well as genetic and transport phenotype
characterisation of three different classes of chloride channels expressed in
Arabidopsis pollen.
GROUP MEMBERS
Ana Bicho (Post-doc)
Claúdia Campos (Post-doc)
Kai Konrad (Post-doc, left in December)
Maria Teresa Portes (Post-doc, started in January)
Michael Wudick (Post-doc, started in February)
Ana Barbara Santos (PhD Student, left in June)
Patrícia Domingos (PhD Student)
Pedro Dias (PhD Student)
Pedro Lima (PhD Student)
COLLABORATORS
Liam Dolan (Oxford University, UK)
Ana Lourenço (FCT/UNL- REQUIMTE, Portugal)
Alice Cheung (University of Massachusstes, Amherst, USA)
Gerhard Obermeyer (University of Salzburg, Austria)
Matthew Gilliham (University of Adelaide, Australia)
Rob Martienssen (Cold Spring Harbor Laboratory, USA)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
We established, for the first time, the existence of reliable and reproducible
anion currents in pollen protoplasts of lily and Arabidopsis. These are grouped
within three populations of currents, are sensitive to Ca2+ and show at least an
equal affinity to chloride and nitrate. These might be the first bona fide chloride
channels in plasma membrane of plant cells. Based on the electrophysiological
profiles, we started a systematic screen of mutants of putative chloride channels.
A SYSTEMS APPROACH TO APICAL CELL GROWTH
The aims of this project are the definition of electrical equivalent models based
on the individual fluxes described; modelling of internal ion concentrations
based on membrane activity, and the description of glutamate receptors as possible
calcium channels in pollen. We established numerical methods to model
how membrane activity results in specific patterns of cytosolic free concentration
of a given ion.
Based on experimental data from tobacco and lily, these models seem to be a
good representation for Ca2+ and pH dynamics. The model appears to predict
that observed proton fluxes at the plasma membrane are sufficient to explain
the cytosolic choreography of this ion. On the contrary, intracellular sequestration,
besides plasma membrane activity, is needed needs to be considered to
explain cytosolic free Ca2+.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
37

TELOMERES
AND GENOME STABILITY
Miguel Godinho Ferreira Principal Investigator
PhD in Cell Biology, University College London, UK, 1999
Post-doc, LRI - Cancer Research UK, London, UK
Post-doc, University of Colorado Health Sciences Centre, Denver, USA
Principal Investigator at the IGC since 2006
link to external website
The strongest risk factor for cancer is age, with 75 per cent of cases diagnosed
in people aged 60 and older. Thanks to our ever-increasing knowledge of tumour
formation, emergent therapies have improved our ability to fight cancer.
Our challenge now lies in understanding the molecular mechanisms responsible
for ageing in order to reduce the lifetime risk for cancer, leading to a healthier
life. Telomeres protect the ends of linear eukaryotic chromosomes from being
recognized as deleterious DNA double strand breaks (DSB). Just a single DSB is
able to stop cell division and activate repair processes. In contrast, all telomeres
prohibit DNA repair, as this may lead to chromosome-end fusions - a source of
genomic instability and a step in tumorigenesis. Our goal is to investigate the
mechanisms underlying chromosome-end protection and the outcomes of its
failure, from the cellular level to the organism level. Ultimately, we aim to prevent
the incidence of cancer associated with ageing.
THE ROLE OF TELOMERES IN AGEING AND CANCER
To analyse the consequences of telomere dysfunction in the whole organism,
we have chosen to work with zebrafish, an organism with naturally shorter telomeres.
Our goal is to use the knowledge acquired on the molecular nature of
telomere protection to understand the consequences of its failure at the organism
level. Our fundamental hypothesis implies that telomere dysfunction signals
a cascade of events that triggers cellular senescence and organism ageing. We
aim to test whether telomere protection in a few key tissues will postpone ageing
in the whole organism and, as a consequence, reduce the frequency of ageassociated
diseases, in particular, cancer. We will test this idea by manipulating
telomere dysfunction (in a time- and tissue-specific manner), using transgenic
zebrafish.
We have two main projects running in our lab. The first concerns the broader
question of whether telomere defects are cell-autonomous or, alternatively,
whether telomere dysfunction acquired in specific tissues somehow signals
other organs, thereby coordinating organism ageing. The second question relies
on use of telomerase-mutant zebrafish to genetically determine the stage
at which telomerase expression is required during cancer development, using
an established model of invasive melanoma.
CONSEQUENCES OF GENOME INSTABILITY TO ADAPTATION AND SPECIATION
As a consequence of telomere deprotection, chromosomes undergo breakagefusion-bridge
cycles resulting in gross chromosome rearrangements (GCRs).
Even if most of these events are deleterious, several clones survive when telomere
function is restored. GCRs comprise the chromosome instability observed
in most human cancers. Similar to cancer cells, we propose that GCRs, when not
lethal, may be adaptive and causative of reproductive isolation in speciation
evolutionary processes. We will investigate how chromosome rearrangements
impact on cell proliferation and adaptation. We will use fission yeast as a biological
model to manipulate genomic instability.
GROUP MEMBERS
Catarina Henriques (Post-doc)
Clara Reis (Post-doc)
Tiago Carneiro (Post-doc)
Ana Teresa Avelar (PhD Student)
Hugo Almeida (PhD Student)
Madalena Carneiro (PhD Student, started in June)
Joana Nabais (Trainee)
COLLABORATORS
Isabel Gordo (IGC, Portugal)
António Jacinto (CEDOC –Centre for Chronic Diseases, Portugal)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Pecha Kucha at Researchers' Night, Pavilhão do Conhecimento, Lisbon,
September
We use fission yeast to understand the molecular nature of telomere protection
(in the top two pictures, the sub-telomeres of chromosome III are stained in green,
highlighting a telomere fusion. Red - SPB and blue - DNA).
We use zebrafish to study the consequences of telomere dysfunction in cancer and
ageing (the two pictures show crypts and villi of the intestine with proliferating
cells in red and apoptotic cells in green. Blue - DNA).
We generated ten GCR-containing S. pombe strains (2 inversions and 8 translocations)
using a pre-established Cre-loxP system. These GCRs constitute the
sole difference from the parental wt strain. We show that for three specific
translocations, chromosome structure is required for optimal growth. In contrast,
the remaining GCRs are neutral in normal growth conditions. As expected,
we observed reduced viability of offspring in hybrid crosses that varied from
10-40%.
MODEL FOR THE NON-CELL AUTONOMOUS EFFECTS OF TELOMERE SHORTENING
IN AGEING.
Cell divisions erode telomeres in proliferative tissues. In time, non-proliferative
tissues become damaged and the whole organism wastes.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
38

GENOME-WIDE ANALYSIS OF TELOMERE PROTECTION IN S. pombe
We aim to carry out a whole genome screen for genes involved in chromosomeend
protection, to characterise telomere length and the localisation of the
newly identified factors with telomeres. Finally, we aim to study the physical
interactions between telomere components.
We started using the fission yeast whole genome deletion library looking for
telomere protection factors by southern blot on the available ca. 3000 viable
mutants. All telomere protection mutants described to date are non-essential,
thus this strategy should produce several remaining players. Presently, we have
screened 80% of the deletion library.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
39

COLLECTIVE
DYNAMICS
Gabriela Gomes Principal Investigator
PhD in Mathematics, University of Warwick, UK, 1993
Post-doctoral Researcher, Mathematics Institute, University of Warwick
Wellcome Trust Research Training Fellow in Mathematical Biology, Department of Biological Sciences, University of Warwick
Principal Investigator at the IGC since 2002
We study collective phenomena, such as self-organisation, criticality, and pattern
formation, arising from spatial and temporal constraints in physical and
biological systems, with a current focus on infectious disease ecology and evolution.
The central theme of our research derives from a conceptual model of
partial immunity whose collective outcome - the reinfection threshold - underlies
a phenomenological transition in epidemic dynamics, with practical implications
ranging from extreme geographical variability in the effect of vaccination
programmes to destabilised transmission favouring polymorphism in antigenically
diverse pathogens. We are interested in refining concepts and methodologies
by performing specific experiments in the laboratory and in natural
populations.
MOLECULAR EPIDEMIOLOGY OF MYCOBACTERIUM TUBERCULOSIS IN PORTUGAL:
IMPLEMENTING AND ANALYSING A DATABASE
We propose to genotype all the strains from sputum of smear positive pulmonary
tuberculosis cases with recent methods based on the variability of mycobacterial
interspersed repetitive units (MIRU) and variable number tandem
repeats (VNTR). A database that includes mycobacterial genotype and clinical
and demographic information about patients will be implemented, constituting
a valuable resource for molecular epidemiology studies, transmission models
and applied research on mycobacterial evolution and pathogenesis.
A total of 2286 isolates of M. tuberculosis DNA were genotyped for 90 SNPs.
About 300 strains were genotyped in the first year and 743 strains were genotyped
during the second year. In the last period of the project, 1239 more samples
were included. Increasing the number of genotyped strains is our immediate
goal and will allow us to infer on the genetic diversity of M. tuberculosis
circulating in the Portuguese population.
EXPLORING PATHOGEN DIVERSITY IN DISEASE EPIDEMIOLOGY
AND VACCINE RESEARCH
Viruses, bacteria and parasitic pathogens have evolved multiple strategies to
evade innate and acquired immune responses, facilitating transmission, allowing
the establishment of persistent and recurrent infections, and often hampering
the development of effective vaccines. Antigenic variation of immune
response targets is one such pathogen strategy that can only be confronted
with the support of a highly specialised research programme combining basic
and applied research. This is the theme of this project. The team integrates basic
research in infection, population genetics, and mathematical epidemiology,
with a range of practical aspects of experimental design from the laboratory
to the field. The overall research strategy is to unravel the molecular bases and
epidemiological significance of immunity in order to guide vaccine design and
deployment.
GROUP MEMBERS
João Sollari Lopes (Post-doc, started in April)
Ana Isabel Franco (Post-doc, started in September)
Cátia Bandeiras (Trainee, started in December)
Delphine Pessoa (Trainee)
Bruno Ceña (Trainee)
Caetano Souto Maior Mendes (Trainee, started in October)
COLLABORATORS
José Pereira-Leal (IGC, Portugal)
Isabel Marques (IGC, Portugal)
Carlos Penha-Gonçalves (IGC, Portugal)
Lounes Chikhi (IGC, Portugal)
Ana Godinho (IGC, Portugal)
Anabela Miranda
(INSA - Instituto Nacional de Saúde Dr. Ricardo Jorge, Portugal)
Ana Abecasis (CMDT-IHMT - Instituto de Higiene e Medicina Tropical,
Portugal)
Diogo Pinheiro (ISEG - Instituto Superior de Economia e Gestão, Portugal)
Raquel Sá-Leão (ITQB - Instituto de Tecnologia Química e Biológica,
Portugal)
Cláudia Codeço (Fundação Oswaldo Cruz, Brazil)
Alessandro Vespignani (Institute for Scientific Interchange, Italy)
Lewi Stone (Tel Aviv University, Israel)
Dirk Brockmann (Max Planck Institute Gottingen, Germany)
Ronald Smallenburg (Grote Griepmeting, The Netherlands)
John Edmunds (London School of Hygiene and Tropical Medicine, UK)
Olof Nyrén (Swedish Institute for Infectious Disease Control, Sweden)
Marc van Ranst (Rega Institute for Medical Research, Belgium)
Shlomo Havlin (Bar Ilan University, Israel)
Stefano Merler (Fondazione Bruno Kessler, Italy)
Daniele Miorandi (Center for Research and Telecommunication
Experimentation for NETworked communities, Italy)
Mário Silva (Faculdade de Ciências, Universidade de Lisboa, Portugal)
Natalia Mantilla (Universidad Nacional Autónoma de México, México)
Glória Teixeira (Universidade Federal da Bahia, Brazil)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Framework Programme 7, European Commission
We compared key parameters underlying pneumococcal transmission in Portuguese
and Finnish day care centres using a continuous-time event history model
in a Bayesian framework. We developed mathematical and statistical models to
elucidate the design of novel pre-clinical and clinical trials to assess intervention
efficacy both in the laboratory and in the field. The new designs are being
refined using Drosophila-Wolbachia as an experimental system.
EPIWORK - DEVELOPING THE FRAMEWORK FOR AN EPIDEMIC FORECAST
INFRASTRUCTURE
In recent years a huge flow of quantitative social, demographic and behavioural
data is becoming available, spurring the quest for innovative technologies that
can improve the traditional disease-surveillance systems, providing faster and
better localised detection capabilities and resulting in a broad practical impact.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
40

Improved ICT techniques and methodologies support the inter-linkage and integration
of datasets causing a qualitative change in the ways we can model epidemic
processes. The EPIWORK project proposes a multidisciplinary research
effort aimed at developing the appropriate framework of tools and knowledge
needed for the design of epidemic forecast infrastructures. The research considers
most of the much-needed development of modelling, computational and
ICT tools.
We have focused on two specific project deliverables:
1. Models of disease transmission under seasonality and other external drivers;
2. Models of spread, impact and evolution of vector-borne pathogens, including
the demography and ecology of host species.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
41

EVOLUTIONARY
BIOLOGY
Isabel Gordo Principal Investigator
PhD in Evolutionary Biology, Edinburgh, 2002
Principal Investigator at IGC since 2004
link to external website
All natural populations have to adapt to new environments. Knowledge of the
genetics of adaptation should provide the centrepiece of a unified theory of
evolution. Despite its extreme importance, the process of adaptation is far from
being understood. For example: What is the rate at which positive Darwinian
selection occurs? Does the rate of adaptation depend on genetic background?
What is the distribution of fitness effects of mutations? Does adaptation involve
the fixation of mutations with small or large effects? How do mutations interact?
What are the relative costs and benefits in bacterial cells with high mutation
rates? These are some of the questions that we try to address.
ANTIBIOTIC RESISTANCE AND THE GEOMETRY OF COMPENSATORY EVOLUTION
The distribution of effects of beneficial mutations is key to our understanding
of biological adaptation. Fisher geometrical model of adaptation predicts
that this distribution should have a given functional form and should depend
on the genotype. Yet empirical estimates of this distribution are scarce and its
functional form is largely unknown. Here we study the rate and distribution of
adaptive mutations that compensate for the effect of a single deleterious mutation,
which causes antibiotic resistance.
GROUP MEMBERS
Ana Margarida Sousa (Post-doc)
Patrícia Brito (Post-doc)
João Batista (PhD student)
Migla Miskinyte (PhD student)
Sandra Trindade (PhD student)
Catarina Bourgard (Technician)
Maria Azevedo (Technician)
COLLABORATORS
Jocelyne Demengeot (IGC, Portugal)
Karina Xavier (IGC, Portugal)
Miguel Godinho Ferreira (IGC, Portugal)
Paulo Campos (Universidade Federal Rural de Pernambuco, Brasil)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
European Research Council (ERC); European Commission
The following manuscripts have resulted form work carried out up to an including
2011: Sousa, Magalhães and Gordo 2011, Cost of resistance and the geometry
of adaptation Molecular Biology and Evolution; Trindade, Sousa and Gordo
Robustness in Antibiotic Resistance (submitted). Silva RF, Mendonça SC, Carvalho
LM, Reis AM, Gordo I, Trindade S, Dionisio F. PLoS Genet. 2011 Jul; 7(7):e1002181.
ADAPTATION WITHIN ECOSYSTEMS
Experimental evolution with bacteria presents us with the opportunity to directly
measure key parameters and to test theoretical predictions about the
genetic basis of adaptive evolution in increasingly complex ecosystems. As
Dobzansky pointed out “The greater the diversity of inhabitants in a territory,
the more adaptive opportunities exist in it.” The main goal of this research project
is to measure rates and effects of adaptive mutations, as well as patterns of
epistasis amongst beneficial mutations in different environments with different
strengths of abiotic versus biotic interactions. In this way the importance of
ecology is increasingly emphasized so as to understand its impact on the statistical
laws governing adaptation.
The following manuscripts have been completed: Trindade, Sousa and Gordo
(submitted), Robustness and Stress in Antibiotic Resistance; Gordo and Campos
(submitted), Evolution of clonal populations approaching a fitness peak; Batista,
Sousa, Bergman, Xavier, Demengeot and Gordo, Adaptation of Escherichia coli
in its natural ecosystem, and M Miskinyte, ML Bergman, I Caramalho, S Magalhães,
J Demengeot and I Gordo Rapid microbial adaptation to escape the sentinels
of innate immunity.
ADAPTATION OF COMMENSAL BACTERIA TO THE MAMMALIAN GUT
The conduction of this project will for the first time determine the dynamics
of adaptation of E. coli in mice bearing a normal immune system and a complex
microbiota and determine the importance of clonal interference during
adaptation in vivo. Next, it will determine the contribution of the microflora on
these dynamics. Finally, the possible double-edged contribution of the immune
system, an original hypothesis, will be formally tested. This work will also open
new avenues for the community and for the three groups involved. Future investigations
will likely address the nature of the mutations, the effect of specific
bacterial species and variants and the precise immune mechanism behind the
selective pressure. This project was started in 2011
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
42

ACTIN
DYNAMICS
Florence Janody Principal Investigator
PhD in Cell biology, Structural Biology and Microbiology, Université de la Méditerranée, France, 1999
Research Associate, Developmental Biology Institute of Marseille Luminy (IBDML), France
Research Associate, Skirball Institute, New York, USA
Principal Investigator at the IGC since 2006
The actin cytoskeleton controls numerous cellular processes. Actin filaments
(F-actin) are not found in the cells as disorganised mesh-works, but rather as
networks with precise organisations, assembled in specific locations within the
cell cytoplasm. For instance, at least 15 distinct actin filament structures have
been identified in mammalian cells in culture, but it is likely that many more exist.
Numerous lines of evidence indicate that the geometrical, mechanical and
dynamic properties of each F-actin network are specifically adapted to perform
a particular cellular function.
In order to understand the cell biology and pathologies linked to the actin microfilament
system, we aim to reveal mechanisms that control actin filament identity
in epithelia and characterise the function of distinct F-actin networks, in particular,
in mediating signal transduction pathways involved in tissue growth control.
ACTIN-CAPPING PROTEIN AND THE HIPPO PATHWAY REGULATE F-ACTIN
AND TISSUE GROWTH IN DROSOPHILA
The actin cytoskeleton is a key cellular component, controlling numerous processes
that include the generation and maintenance of cell morphology and
polarity, endocytosis, intracellular trafficking, contractility and cell division.
Actin filament (F-actin) growth, stability, disassembly and organisation into
higher-order networks are controlled by a plethora of cytoskeletal proteins,
strongly conserved between species. There is little doubt that several of these
proteins are positively associated with cancer. However, the contribution of
F-actin dynamics to oncogenic transformation is far from clear.
GROUP MEMBERS
Beatriz García Fernández (Post-doc)
Catarina Bras Pereira (Post-doc)
Pedro Miguel Gaspar (PhD Student)
Barbara Jezowska (PhD Student)
Ana Rita Amândio (Technician, started in November)
COLLABORATORS
Fernando Casares (Universidad Pablo de Olavide, Spain)
Nicolas Tapon (Cancer Research UK, London, UK)
Jochen Guck (IPATIMUP Porto, Portugal)
Laurent Perrin (Technological Advances for Genomics and Clinics,
INSERM U928, Marseille, France)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Media interviews (May, July, September)
Talks for school students, IGC (December)
We aimed in this project to get insight into the role of the actin microfilament
system in preventing oncogenic transformation. We took advantage of Drosophila
genetics, which allows easy manipulation of gene expression in the context
of intact epithelia, to identify ABPs that are involved and determine how
tumor suppressors and oncogenes regulate the actin cytoskeleton.
The conserved Hippo tumor suppressor pathway is a key kinase cascade that
controls tissue growth. Our work reveals an interdependency between Hippo
signaling activity and actin filament dynamics in which actin-Capping Protein
(CP) and Hippo pathway activities inhibit F-actin accumulation, and the reduction
in F-actin in turn sustains Hippo pathway activity, preventing Yorkie nuclear
translocation and up-regulation of proliferation and survival genes (García
Fernández et al., 2011).
A DUAL FUNCTION OF DROSOPHILA CAPPING PROTEIN
ON DE-CADHERIN MAINTAINS EPITHELIUM INTEGRITY
AND PREVENTS JNK-MEDIATED APOPTOSIS.
E-Cadherin (E-Cad) plays a pivotal role in epithelial cell polarity, cell signaling and
tumor suppression. We have shown that Capping Protein (CP), which prevents
F-actin polymerisation, stabilises DE-Cad at cell-cell junctions and inhibits upregulation
of the DE-cad gene. DE-Cad would otherwise provide an active signal,
which promotes JNK-mediated apoptosis. However, when cells are kept alive,
JNK is converted into a potent inducer of proliferation (Jezowska et al., 2011).
ACTIN FILAMENT DYNAMICS TRIGGERS NEOPLASTIC TUMOR
TRANSFORMATION DOWNSTREAM OF THE SRC PROTO-ONCOGENE.
c-Src is the oldest and most investigated proto-oncogene that is activated in a
broad range of cancer types. Our work reveals that in restricted Drosophila epithelia,
over-activation of Src promotes apical F-actin accumulation through the
Tec kinase Btk29A and Rho1. In turn, F-actin appears to have a dual function on Src
signalling activity: it controls the balance between proliferation and cell death and
triggers Src activation through phosphorylation (Jezowska et al., in preparation).
(A-A´ to C-C´) Capping actin filaments inhibits proliferation of "undead" Src overexpressing
tissues. (D) Model of the interplay between F-actin and signaling activity
through Hippo and Src. Hpo activity controls the sub-apical F-actin meshwork,
which regulates Yorkie (Yki) transcriptional activity, while Src, Btk29A and Rho1
regulate the circumferential F-actin cable, which mediates Src signaling activity.
Capping Protein regulates both F-actin networks.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
43

THE HIPPO TUMOR SUPPRESSOR PATHWAY AND THE SRC PROTO-ONCOGENE
REGULATE DISTINCT F-ACTIN NETWORKS.
Eukaryotic cells generate a diversity of F-actin networks. We observed that
Hippo and Src signaling activities control distinct F-actin webs at specific subcellular
locations. Moreover, we identified ABPs specifically involved in mediating
Hpo or Src signaling activities. This argues that the geometrical, mechanical
and dynamic properties of each F-actin network are specifically adapted to
regulate Hippo and Src signaling activities (Gaspar et al., in preparation).
THE EYE SELECTOR GENE DACHSHUND PROMOTES CYTOSKELETAL
REARRANGEMENT AND EXIT FROM THE FURROW STATE.
Despite the fact that epithelium architecture constrains cells in their ability to
move, they can be engaged in a large number of morphogenetic rearrangements
and adopt a different repertoire of cell shape. Actin filaments (F-actin) are major
determinant of cell shape and can form a diversity of networks with precise
mechanical and dynamic properties. Although it becomes increasingly clear that
cell shape has a critical impact on cell differentiation and tissue morphogenesis,
the role of cell architecture in these processes is far from clear.
We aimed in this project to get insight on how F-actin is regulated to promote
cell shape changes and how this impacts on tissue morphogenesis and cell differentiation.
To do so, we used the developing Drosophila eye, to investigate
the role of actin isoforms, actin regulatory proteins, eye selector genes and
signaling pathways in triggering cell shape changes required for neuronal differentiation.
Dachshund (dac), the most downstream element among the known RDGN,
encodes a nuclear protein related to the Sno/Ski protein family of proto-oncogenes.
We found that Dac promotes cell shape required for proper differentiation
of the retina. Our results argue that one function of the Dac nuclear
factor is to regulate cytoskeletal rearrangement required to exit the furrow
state thereby controlling the timing of differentiation (Brás-Pereira et al., in
preparation).
THE RETINAL DETERMINATION GENE DACHSHUND ENSURES PATTERNED CELL
PROLIFERATION BY LIMITING YORKIE FUNCTION
Recent studies have demonstrated an important role for the human Dac homolog
DACH1 in tumorigenesis. We showed that in the Drosophila eye imaginal
disc, Dac suppresses inappropriate tissue growth by inhibiting Yorkie activity,
which mediates Hippo signaling. Since Dac interacts physically with the Yorkiebinding
partner Homothorax, our findings indicate that Dac is recruited to the
promoter of Yorkie targets to inactivate proliferation and survival genes (Brás-
Pereira et al., in preparation).
HOMEOSTASIS OF THE DROSOPHILA ADULT RETINA BY CAPPING PROTEIN
AND THE HIPPO PATHWAY
The conserved Hippo signaling pathway regulates multiple cellular events, including
tissue growth, cell fate decision and neuronal homeostasis. We provide
evidence that the actin cytoskeleton promotes neuronal homeostasis of the
adult Drosophila retina through misregulation of the Hippo pathway. We propose
a model by which F-actin dynamics is involved in all processes that require
the activity of the core Hippo kinase module (Brás-Pereira et al., 2011).
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
44

EPIGENETIC
MECHANISMS
Lars Jansen Principal Investigator
PhD in Molecular Genetics, Leiden University, 2002
Postdoc, Ludwig Institute for Cancer Research, La Jolla, CA, USA
Principal Investigator at the IGC since 2008
In addition to genomic information embedded in the primary DNA sequence,
additional epigenetic information is propagated along cell divisions that “memorises”
gene activity states and specific chromatin structures. Epigenetic inheritance
forms the basis for many aspects of biology that includes development,
gene regulation and disease. Several molecular components such as histone
proteins and modifications thereof have been implicated in this process but in
most cases we don’t understand the logic of how something other than DNA
can be faithfully duplicated when a cell divides. We have a broad interest in how
this works. We use the mammalian centromere as a model for chromatin-based
epigenetic inheritance. We employ molecular genetic and cell biological tools
with a focus on novel fluorescent labelling techniques, high-end microscopy and
the latest tricks in genetic engineering of human cells to tackle a wide range of
problems in this emerging and fascinating area of biology.
DETERMINING THE EPIGENETIC MECHANISM OF CENTROMERE PROPAGATION
The centromere is a unique specialised chromatin domain responsible for driving
chromosome segregation. The centromere complex is maintained epigenetically,
independent of direct DNA sequence information. How this works is poorly
understood. We have devised fluorescent pulse labelling techniques which
have established that the centromeric histone H3 variant CENP-A generates
an extremely stable chromatin structure, consistent with providing epigenetic
identity to the centromere. Replenishment of new CENP-A is tightly coupled to
the cell cycle ensuring synchrony between cell division and centromere propagation.
We focus on determining the mechanism of CENP-A maintenance, and
its cell cycle coupling. We use novel cell-biological tools, human somatic cell
gene knockouts in conjunction with other molecular genetic and biochemical
assays to determine the logic and mechanism of epigenetic centromere maintenance.
We have shown that the Cdk1 and Cdk2 kinases maintain the CENP-A
assembly machinery in an inactive state throughout S, G2 phase and mitosis
thereby restricting CENP-A loading to G1 phase of the cell cycle (Silva et al,
Developmental Cell). In a collaborative effort we have shown that centromeric
DNA transcription is involved in CENP-A assembly by generating a chromatin
structure that allows recruitment of a key CENP-A assembly factor. (Bergman et
al, EMBO Journal).
HISTONE VARIANT ASSEMBLY AND MAINTENANCE ACROSS THE CELL CYCLE
Histone proteins that package DNA into chromatin are implicated in carrying
epigenetic information through locus specific post translational modification or
incorporation of histone variants. We are determining how epigenetic markers
are propagated across mitotic divisions with a specific focus on the histone H3
variants H3.1 and H3.3. These variants are implicated in maintaining centromere
identity and gene activity respectively. We are aiming at developing a temporal
affinity purification strategy that is based on using the SNAP-tag as an affinity
tag. This will allow us to determine protein turnover and assembly at specific
cell cycle positions at gene resolution. This biochemical approach also allows
broadening of our focus and answers critical question e.g. on the H3.3 replacement
histone that is associated with epigenetic memory of gene activity.
GROUP MEMBERS
Luis Valente (Post-doc)
Mariana Silva (PhD student)
Mariluz Gomez (PhD student)
João Mata (Research Technician)
Dani Bodor (Trainee)
COLLABORATORS
Helfrid Hochegger (Sussex Centre for Genome Damage and Stability, UK)
Don W. Cleveland (Ludwig Institute for Cancer Research, San Diego, USA)
Daniel R. Foltz (University of Virginia, USA)
Ben E. Black (University of Pennsylvania, USA)
Genevieve Almouzni (Institut Curie, Paris, France)
Bill Earnshaw (Wellcome Trust Centre for Cell Biology, Edinburgh, UK)
FUNDING
FP7 - Marie Curie Programme, European Commission
European Molecular Biology Organisation (EMBO)
Fundação para a Ciência e a Tecnologia (FCT), Portugal
COUNTING MOLECULES AND CHROMOSOMES.
Fluorescent proteins and cell compartment markers (nucleus - green, cell - red)
are used to accurately determine how much of a specific protein is where in the
cell. Dots are centromeres, protein clusters that organise chromosome segregation
during cell division.
We have developed a protocol to detect and isolate in vivo pulse labelled histone
proteins in chromatin. Using this method we are in the process of measuring
histone variant turnover rates at gene resolution and are determining the
role of gene transcription in histone dynamics. In a collaborative effort we have
determined the role of histone H3.1 and H3.3 specific chaperones in chromatin
assembly (Ray-Gallet, Mol Cell).
DNA staining of specific chromosomes (green and red dots) reveals normal diploid
(top) or aberrant chromosome numbers after severe mitotic failure.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
45

ORGANOGENESIS
Joaquín Rodríguez León Principal Investigator
PhD in Biology, University of Extremadura, Spain, 2000
Principal Investigator at the IGC since 2008
Our group focuses on the study of the cellular and molecular mechanisms controlling
limb development and fin regeneration. We are trying to understand
how the main signalling centre in limb development, the Apical Ectodermal
Ridge (AER), is established and maintained through development and how different
molecules, namely those related to stemness, are involved in these processes.
Also, we have developed a line of research directed to depict how ion
dynamics can control limb development, digit differentiation and fin regeneration.
In these studies we use the chicken and zebrafish embryos as well as adult
zebrafish as animal models.
ROLE OF STEMNESS GENES DURING FORMATION OF COMPLEX ORGANS
This project is framed into a general line of work in our lab that focuses on
the study of different genes that are involved in the maintenance of stemness
in vitro, and their in vivo role during development of complex organs. We are
studying how oct4 plays a role in the formation of limbs during vertebrate
development. Our main objective is to unveil how oct4 controls the activity of
a signalling centre essential for limb formation, the Apical Ectodermal Ridge
(AER). The aims of this project are:
GROUP MEMBERS
Ana Catarina Certal Afonso (Post-doc, left September)
Rui Castanhinha (PhD Student)
Joana Monteiro (External PhD student)
Rita Felix (Masters Student)
Ana Rita Aires (Research Technician)
COLLABORATORS
Yolanda Gañán Presmanes (University of Extremadura, Spain)
Domingo Macías Rodríguez (University of Extremadura, Spain)
Michael Levin (Tufts University, USA)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Talk for school students, Colegio Arias Montano, Badajoz, Spain (April)
Talk for school students, Escola Santo António e Escola António Aleixo,
Figueira de Castelo Rodrigo, Portugal (November)
1. To characterise oct4 expression during limb bud development;
2. To characterise the dynamics of proliferation versus apoptosis in the Apical
Ectodermal Ridge during limb bud development;
3. To understand the role of oct4 during limb bud development and its implication
in the maintenance of AER structure, function and cell behaviour;
4. To correlate the activity of FGFs, Wnts and RA and the control of oct4
expression with the AER structure, function and cell behaviour.
We have found that Wnts and Fgfs control and maintain oct4 expression in the proliferative
areas of the AER. On the contrary, BMPs and Retinoic Acid signaling act
as negative factors that abolish oct4 expression in the apoptotic areas of the AER.
We have also performed experiments involving pulses of BrdU and these manipulations
show that proliferative cells in the dorsal and ventral sides of the AER will
migrate towards its centre and will die by apoptosis. Manuscript is in preparation.
ION DYNAMICS DURING FIN REGENERATION
With this project we intend to assess the role of electric currents as coordinating
signals during the re-establishment of the P-D axis after amputation of
adult vertebrate appendages. We want to extend the current knowledge on the
molecular and cellular bases of bioelectric signals as well as the mechanisms
that convert them into cellular responses. The aims of this project are:
Limb bud after oct4 overexpression and double in situ for fgf8 (orange) and msx-1
(blue).
1. To describe the ion composition of electric currents associated with the regeneration
of caudal fins and to generate a spatial-temporal map of the intracellular
and extracellular dynamics of particular ion species during regeneration;
2. To unveil the molecular and cellular bases of ion dynamics associated with
regeneration;
3. To understand the role of specific ion transporters in the regeneration
mechanism;
4. To establish a link between ion dynamics and known molecular pathways
involved in the regeneration process.
We have demonstrated that during regeneration, a proton outward flux gradient is
established along the proximo-distal axis. Moreover, we have identified the V-AT-
Pase as the most likely molecular source that triggers the detected regenerationspecific
H+ efflux. Inhibition of this ion pump decreases regeneration rate. Hence,
we suggest that V-ATPase mediated proton flux in involved in the spatial coordination
of genes that will dictate the position-dependent rate of regeneration.
Scanning electron microscopy micrograph showing the surface of the regenerating
blastema in a zebrafish caudal fin 6 hours after amputation.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
46

SYSTEMS
NEUROSCIENCE
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Zachary Mainen Principal Investigator
PhD in Neurosciences, University of California, San Diego, 1995
Associate Professor, Cold Spring Harbor Laboratory, New York, USA
Head of the Champalimaud Neuroscience Programme at IGC
Principal Investigator at the IGC since 2007
link to external website
We are interested in understanding the principles underlying the complex adaptive
behaviour of organisms. Starting with quantitative observations of animal
behaviour, we aim to integrate quantitative cellular and systems level experimental
analysis of underlying neural mechanisms with theoretical, ecological
and evolutionary contexts. Rats and mice provide flexible animal models that
allow us monitor and manipulate neural circuits using electrophysiological, optical
and molecular techniques. We have made progress using highly-controlled
studies of a simple learned odour-cued decision task and are extending our
focus toward more complex behaviours. Projects in the lab are wide-ranging
and continually evolving. Current topics include:
1. Olfactory sensory decision-making;
2. The function of the serotonin system;
3. The role of uncertainty in brain function and behaviour;
4. The neural dynamics of choice.
OPTOGENETIC IDENTIFICATION AND CONTROL OF SEROTONIN NEURONS
IN BEHAVING ANIMALS
Serotonin (5-HT) is an important neurotransmitter implicated in a wide variety
of physiological functions and psychopathologies, but whose function is not
well understood. Critically, very little is known about the activity of serotoninreleasing
neurons in the brain. This problem is greatly exacerbated by the difficulty
in identifying these neurons during physiological recordings. To address
these problems, we will develop and validate optogenetic methods that target
5-HT neurons, gaining access to record and perturb this system optically with
high temporal and genetic specificity. We will combine these tools with behavioural
analysis and electrophysiological recordings toward understanding the
role of 5-HT in adaptive behaviour. Our aims are to use these approaches to
stimulate, silence and monitor 5-HT function in the context of spontaneous
behaviours, value-related decision-making, sensorimotor function and behavioural
timing.
GROUP MEMBERS
Cindy Poo (Post-doc, started in May)
Eran Lottem (Post-doc, started in January)
Enrica Audero (Post-doc/Project manager, started in February)
Eric Dewitt (Post-doc)
Magor Lorincz (Post-doc)
Hope Johnson (Post-doc)
Masayoshi Murakami (Post-doc)
Guillaume Dugué (Post-doc)
Niccolò Bonacchi (PhD Student)
Ana Rita Fonseca (PhD Student)
André Mendonça (PhD Student)
Maria Inês Vicente (PhD Student)
Patricia Correia (PhD Student)
Sara Matias (PhD Student)
Gil Costa (PhD Student)
COLLABORATORS
Adam Kepecs (Cold Spring Harbor Laboratory, USA)
Alex Pouget (Department of Brain and Cognitive Sciences,
University of Rochester, USA)
Matthieu Luis (Centre for Genomic Regulation (CRG), Barcelona, Spain)
Trevor Sharp (Department of Pharmacology, University of Oxford, UK)
FUNDING
European Research Council (ERC), European Commission
Human Frontiers Science Programme (HFSP)
Champalimaud Foundation (CF), Portugal
Fundação para a Ciência e a Tecnologia (FCT), Portugal
We continued to validate techniques for stimulating light-gated channelrhodopsin-2
in 5-HT neurons, using slice physiology, pharmacology, microdialysis,
in vivo recordings and demonstrated a light-activated field potential as a measure
of 5-HT stimulation (manuscript in preparation). We found effects of 5-HT
stimulation on olfactory neural activity in the piriform cortex. We demonstrated
a new system for chronically monitoring neural activity in genetically-defined
neuronal populations.
OLFACTORY OBJECTS AND DECISIONS:
FROM PSYCHOPHYSICS TO NEURAL COMPUTATION
Object recognition is an important and difficult problem solved by the nervous
system. According to theoretical accounts, object recognition can be understood
as a process of probabilistic inference. Under this hypothesis, complex
stimuli are represented using a probabilistic population code. To link these normative
ideas to specific neurophysiological and behavioural predictions, we are
formalising them using computational models. Experimentally, our primary goal
is to monitor and perturb object representations in the functioning, computing
brain. To this end, we deploy olfactory psychophysical tasks in rats, which formalise
complex real-world problems. By combining such quantitative paradigms
with large-scale neural ensemble recordings in the olfactory cortex, we can
study how populations of neurons encode and process complex odour scenes,
attempt to account for behavioural performance, and test the predictions of
our theoretical models.
IGC ANNUAL REPORT ‘11
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47

We compared speed-accuracy trade-offs (SATs) in odour detection and categorisation
and found large differences between tasks, demonstrating that SAT is
problem-specific and suggesting that the locus of performance-limiting noise
is a critical variable (manuscript in preparation). We developed a computational
model of these tasks, which can be fit to the data, and which has allowed us to
formalise these hypotheses.
ACTION SELECTION AND ACTION TIMING IN THE PREMOTOR CORTEX
Executing the right action at the right moment is important for adaptive behaviour.
Thus, not only how we choose one action among multiple options but also
how we determine the timing of actions are fundamental questions.
Our goal is to understand what features of future actions are represented in
the neuronal firing patterns in these areas, and how the interaction between
neurons gives rise to the action selection and action timing processes.
To achieve this goal, we are using multiple single-unit recording techniques
in behaving rodents. By correlating the activity of neurons with the animal’s
behaviour, we are seeking to understand the internal representation of future
actions in the motor cortex. Furthermore, by analysing the relationships of
spiking activity amongst multiple neurons, we hope to gain insight into computations
within the microcircuits in the motor cortex. Finally, we will apply
optogenetic techniques to perturb specific circuits and observe the impact on
behaviour.
We analysed neural correlates of action timing in the premotor cortex, documenting
two classes of waiting-time predictive neurons and a dynamical systems
analysis of the ensemble activity (manuscript submitted). We also developed a
task in which we can manipulate the availability of potential action options. We
began testing optogenetic interventions in these contexts.
EVALUATING THE RELIABILITY OF KNOWLEDGE:
NEURAL MECHANISMS OF CONFIDENCE ESTIMATION
Humans and other animals must often make decisions on the basis of imperfect
evidence. What is the neural basis for such judgments? How does the brain
compute confidence estimates about predictions, memories and judgments?
Previously, we found that a population of neurons in the orbitofrontal cortex
(OFC) tracks the confidence in decision outcomes. We are seeking to extend
these observations by testing whether confidence-related neural activity in the
OFC is causally related to confidence judgments. We are also addressing how
the uncertainty about a stimulus in the course of decision-making is computed
in olfactory sensory cortex. We are currently establishing similar confidencereporting
tasks in humans and testing them in a range of behaviours. These
experiments will give us further insights into the nature of the neural processes
underlying confidence estimation.
In rats, we used chronic multi-electrode recordings to assay neural ensemble
function in the olfactory tubercule of rats performing a confidence reporting
task (study in progress). We also found that inactivation of the rat orbitofrontal
cortex impairs confidence reporting but not choice behaviour (manuscript under
review). In humans we tested confidence reporting tasks similar to those we
deployed in rats under several different psychophysical paradigms.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
48

PATTERNING
AND MORPHOGENESIS
Moisés Mallo Principal Investigator
PhD in Molecular Biology, Santiago de Compostela, Spain, 1991
Postdoctoral Fellow, Roche Institute of Molecular Biology, Nutley, NJ, USA
Junior Group Leader, Max Planck Institute of Immunobiology, Freiburg, Germany
Head of the IGC Transgenics Unit
Principal Investigator at the IGC since 2001
Our group is interested in several aspects of vertebrate embryonic development.
The ultimate goal of our research is to understand the molecular mechanisms
that translate patterning information into morphogenetic processes
during formation of the vertebrate embryo. For a number of years, we have
explored different developmental processes, including ear formation, neural
crest induction/migration and differentiation of branchial arches. Our most
recent work is focused on the development and evolution of the vertebrate axial
skeleton, mostly focused on the role that Hox genes play in these processes.
We are particularly interested in understanding the molecular mechanisms that
mediate Hox activity, with special focus on the functional interactions between
Hox genes and chromatin.
GROUP MEMBERS
Ana Cristina Santos (Post-doc)
Ana Casaca (Post-doc)
Arnon Jurberg (PhD Student)
Ozlem Isik (PhD Student)
Ana Nóvoa (Research Technician)
Andreia Nunes (Trainee)
COLLABORATORS
Sara Monteiro (Instituto Superior de Agronomia de Lisboa, Portugal)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
THE ROLE OF SPECIFIC PEPTIDE MOTIFS AND POST-TRANSLATIONAL
MODIFICATIONS IN ACTIVITY OF HOX GROUP 10 GENES
Functional assays using transgenic embryos showed that different Hox genes
display remarkable degrees of specificity. A paradigmatic example of this is the
ability of Hox10 genes to block rib formation, a property that is not shared by
any other Hox gene tested under the same assay conditions. We set to identify
the characteristics that provide Hox10 proteins their rib-repressing activity.
We searched for motifs shared by Hox10 genes, which are not shared by other
Hox proteins. We identified at least two of them. In this project we are analysing
the contribution of these motifs to the protein's function by mutating them or
their introduction into another Hox protein without rib-repressing properties
to test their functional effects. We also want to analyse how these motifs affect
post-translational modifications in these proteins to determine if any of these
modifications is required for the protein's function.
We have shown that one of the motifs that we found to be specific to Hox10
proteins is indeed essential for the rib-repressing activity of these proteins.
M1 needs to be phosphorylated to produce an active Hox10 protein. This motif
interacts with the N-terminal sequences of the protein and with the homeodomain
to modulate the phosphorylation status of two conserved tyrosine
residues that influence the DNA binding properties of the molecule. We have
submitted a paper with these findings.
THE CONTROL OF MYF5 AND MYF6 EXPRESSION BY HOX GENES
We have previously shown that Myf5 and Myf6 expression are controlled by Hox
genes of groups 6 and 10, specifically in the hypaxial myotome. This regulation
is a key element of the mechanism by which genes of those two Hox groups
control rib formation. The control of Myf5/6 expression by Hox genes involves
direct interaction with a specific enhancer located 56 kb upstream of Myf5. In
this process, Hox proteins interact with Pax3, which is also essential to regulate
this enhancer. We now want to understand the mechanisms of this control. Given
the long distance between the Hox/Pax responsive enhancer and the genes it
controls, we hypothesised that part of this control involves modulation of chromatin
structure. In addition, some data suggest that Hox10 genes could act as
pioneer factors to promote or block Pax3 activity on this enhancer. Therefore,
one of the main aims of this project is to determine the effect of Hox and Pax
activity on the chromosome structure at the Myf5/6 locus.
We have generated a BAC reporter assay to study the chromatin structure associated
to the Hox/Pax-responsive enhancer of Myf5. For this, we introduced a
small sequence tag next to the enhancer, in the context of a BAC that contains
all relevant areas of the Myf5 locus required to control developmental expression
of this gene. We have created transgenic mouse lines with these BACs,
which will be used to analyse the effect of Hox activity on the chromosome
structure of the Myf5 genomic region.
Wild Type
Mouse-Type H1 enhancer
Dll1-mHoxa10
Dll1-snkHoxa10
Skeletons of a wild type embryo and of two transgenic embryos expressing either
the mouse or snake Hoxa10 genes (Dll1-mHoxa10 and Dll1-snkHoxa10, respectively).
The data shows that the snake Hoxa10 gene is able to block rib formation as efficiently
as its mouse counterpart.
Snake-Type H1 enhancer
β-galactosidase expression from BAC reporter transgenes in which the
β-galactosidase gene was inserted into the Myf5 transcription unit. In the embryo
on the left, the BAC contains the Hox-responding H1 enhancer normally found
in the mouse genome. In the embryo on the right, the H1 enhancer of the BAC
was modified to introduce the polymorphism that we have identified in the snake
genome. In the latter embryo, expression is extended in the hypaxial myotome at
the hind limb level, showing that this polymorphism is indeed functional in vivo.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
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HOXA10 AND THE EVOLUTION OF THE VERTEBRATE BODY PLAN
One of the functions of Hox genes of the paralogue group 10 during patterning
of the axial skeleton is to block rib formation. This function is essential for the
formation of the rib-less areas of the vertebral column caudal to the ribcage,
such as the lumbar vertebrae. It has been shown that in snakes Hoxa10 is expressed
within the rib-forming area, suggesting that in snakes this gene has lost
the ability to block rib formation. Whether this is an intrinsic property of the
protein itself or due to alterations in the networks downstream to this gene,
remains to be determined. In this project we aim at understanding this problem.
We found that the snake Hoxa10 blocks rib formation when assayed in mouse
embryos. Therefore, the absence of activity in the snake is not due to intrinsic
properties of the protein. We identified a polymorphism in the Hox-responsive
enhancer of Myf5 that renders the enhancer unable to bind Hox proteins. When
assayed in transgenic mice using a BAC reporter approach, we saw that this
polymorphism is functionally relevant, which explains the inability of Hoxa10 to
block rib formation in snakes.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
50

EARLY FLY
DEVELOPMENT
Rui Gonçalo Martinho Principal Investigator
PhD in Biology, University of Sussex, UK, 2000
Associate to Howard Hughes, Skirball Institute - New York Medical Center, NYC, USA
Principal Investigator at the IGC since 2006
Our main research interests relates to mitosis, cell proliferation, and tissue morphogenesis.
More specifically:
1. We are taking advantage of Drosophila melanogaster as a model system
to better define the molecular mechanisms responsible for the correct orientation
of the mitotic spindle during symmetric mitosis of epithelial cells;
2. We want to understand the differential requirements of protein N-terminal
acetylation in somatic and germ-line stem cells mitosis;
3. Explain why a known human tumour suppressor gene is specifically important
for the onset of zygotic expression and tissue morphogenesis in the
earliest stages of Drosophila development.
GROUP MEMBERS
Leonardo Gaston Guilgur (Post-doc)
Paulo Costa(Post-doc, started in September)
Tania Ferreira (PhD Student)
Pedro Prudêncio (Laboratory Manager)
Ana Ribeiro (Trainee, started in November)
Barbara Kellen (Trainee)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
CHARACTERISATION OF MESENCHYMAL TO EPITHELIAL TRANSITION
IN Drosophila melanogaster
This project aims at defining the role of atypical protein kinase C (aPKC) during
tissue morphogenesis, MET, and cell proliferation (submitted manuscript).
ANALYSIS OF THE ROLE OF N-TERMINAL ACETYLTRANSFERASES
DURING DROSOPHILA DEVELOPMENT
Defining the role of N-terminal acetylation during cell proliferation is the main
objective of this research project. Findings have been submmited for publication.
CONSTRAINTS ON GENE EXPRESSION DURING EARLY EMBRYONIC
DEVELOPMENT
The main aim is the characterisation of Drosophila early zygotic transcription.
We identified a mutant that is specifically defective for pre-mRNA splicing of
early zygotic transcripts.
IGC ANNUAL REPORT ‘11
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DEVELOPMENT,
EVOLUTION
AND THE ENVIRONMENT
Christen Mirth Principal Investigator
PhD in Zoology, University of Cambridge, UK, 2002
Post-doctoral associate, Department of Zoology, University of Wahsington, Seattle, USA
Research Specialist, Janelia Farm Research Campus, HHMI, Ashburn, USA
Principal Investigator at the IGC since 2010
link to external website
Our lab studies the regulation and evolution of environmentally-dependent
traits in species from the genus Drosophila. Recently, our efforts have focused
on two traits that depend on nutritional cues:
1. Body size;
2. Larval foraging behaviour.
We use the genetic tools available in Drosophila melanogaster to dissect how environmental
signals, like nutrition, regulate larval growth and foraging choices.
By analysing the changes in these mechanisms across species, we hope to identify
how these environmentally-dependent traits evolve to create species-specific
differences in foraging behaviour and adult body size.
GROUP MEMBERS
Takashi Koyama (Post-doc)
Marisa Oliveira (PhD Student)
Cláudia Mendes (PhD Student, started in April)
Sara Lennox (Technician)
Marisa Rodrigues (Trainee)
COLLABORATORS
Alexander Shingleton (Department of Zoology, Michigan State University, USA)
Élio Sucena (IGC, Portugal)
Marta Zlatic (Janelia Farm Research Campus, Howard Hughes Medical
Institute, USA)
FUNDING
Calouste Gulbenkian Foundation, Portugal
NUTRITION-DEPENDENT REGULATION OF BODY SIZE
IN Drosophila melanogaster
Organisms of all phyla regulate their body size in response to a number of environmental
factors, including nutrition. Both the rate of growth and the length of
the growth period determine final body size. Nutrition regulates growth rates
via the insulin and target of rapamycin (TOR) pathways. In insects, a size-dependent
checkpoint, known as critical weight, determines when growth ceases.
Insulin and TOR signaling in the prothoracic gland (PG) regulates critical weight
by controlling on the production of the steroid hormone ecdysone. Thus nutrition
directly affects both the rate and duration of the growth period. We aim to
understand how nutrition regulates final body size by:
1. Investigating how insulin/TOR controls the nutrition-dependent synthesis
of ecdysone;
2. Determine the role of ecdysone signalling on the growth and differentiation
of the developing adult tissues.
Two manuscripts are in preparations:
Oliveira, M.M., Shingleton, A.W. & Mirth, C.K. (in preparation). How old are you?
A new tool using gene patterning to characterise developmental time in Drosophila
larvae.
Mirth, C.K.,Tang,H.Y., Makhon-Moore, S., Salhadar, S., Riddiford, L.M. & Shingleton,
A.W. (in preparation). Juvenile Hormone controls body size by regulating
insulin signalling in Drosophila.
THE ENVIRONMENTAL REGULATION AND EVOLUTION OF FORAGING
STRATEGIES IN THE GENUS Drosophila
The environment and evolution act to generate a vast diversity of foraging strategies
in insects. We examine two aspects of foraging behaviour: how environmental
cues interact with development to regulate larval foraging behaviour in
D. melanogaster and how behavioural suites evolve to produce differences in
larval foraging strategies between species of the genus Drosophila.
Our most recent efforts investigate the evolution of larval foraging behaviour
using a collection of 47 species of Drosophila. To date, we have analysed all
species for burrowing behaviour. We are continuing our exploration by characterising
the array of behaviours observed when larvae come into contact on
the surface of the food. Exploring these behaviours allows us to generate a
behavioural profile for each species.
We use these profiles to identify closely related species exhibiting divergent
behaviours. Our ultimate goal is to identify genomic sites responsible for the
evolution of foraging strategies. A manuscript is in preparation:
Rivera Alba, M., Kelstrup, H.C.P., Riddiford, L.M. & Mirth, C.K. (in preparation).
The evolution of burrowing behaviour in fruit flies from the genus Drosophila.
Knocking down FoxO and Usp in the prothoracic gland (PG) causes premature
expression of Senseless (Sens) in wing discs of larvae starved of protein. A) A
wing disc from a control larva (PG>). B) A wing disc from a larva in which FoxO is
knocked down in the PG. C) A wing disc from a larva in which Usp is knocked down
in the PG. D) A wing disc from a larva in which both FoxO and Usp are knocked
down in the PG. Arrows point to Sens positive sensory organ precursors.
IGC ANNUAL REPORT ‘11
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BEHAVIOURAL
NEUROSCIENCE
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Marta Moita Principal Investigator
PhD in Neuroscience, Universidade do Porto, Portugal
Post-doctoral Fellow, Cold Spring Harbor Laboratory, USA
Principal Investigator at the IGC since 2004
link to external website
We are interested in understanding the neural mechanisms underlying behavioural
plasticity using a combination of behavioural, pharmacological, molecular
and electrophysiological tools. In particular, we are studying how prior experience
and how social interactions shape behaviour. To this end, we are studying
fear; both how animals learn to fear cues that are predictive of aversive events
or threats, and how fear can be socially transmitted, i.e. how animal respond to
the distress of con-specifics. We chose fear learning since it is conserved across
species, entailing fast robust learning and very long lasting memories. We are
also studying decision-making in the context of social interactions, using game
theory to test how rats learn and evaluate the payoffs that result from the interaction
with another individual.
NEURAL MECHANISMS OF TRACE AUDITORY FEAR CONDITIONING
This project focuses on the role of different memory systems in trace auditory
fear conditioning (tAFC). We hypothesised that the mechanism underlying the
association between a tone and a shock depends on the length of the trace
interval memory and in the case of long intervals they rely on episodic memory
between the two stimuli, where in the case of a short interval rats rely on working
memory.
GROUP MEMBERS
Kensaku Nomoto (Post-doc)
Ana Pereira (PhD student)
Andreia Pereira (PhD student)
Elizabeth Rickenbacher (PhD student)
Marta Guimarãis (PhD student)
Scott Rennie (PhD student)
COLLABORATORS
Hugh Blair (University of California Los Angeles (UCLA), USA)
Alfonso Renart (Champalimaud Foundation, Portugal)
Susana Lima (Champalimaud Neuroscience Programme, Portugal)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Champalimaud Foundation, Portugal
We have tested the role of contextual learning in auditory trace fear conditioning.
We found that decreasing the saliency of the training environment disrupts
learning to fear a tone that precedes shock by several seconds and that inactivating
the hippocampus does not decrease it further. In addition we are studying
the role prefrontal cortex in trace conditioning by performing single-unit
recordings in this structure during learning.
COOPERATION IN SOCIAL DILEMMAS IN RATS
Game theory has constituted a powerful tool in the study of the mechanisms of
reciprocity. Having shown that, in a Prisoner’s Dilemma game, rats shape their
behaviour according to the opponent’s strategy and the relative size of the
payoff resulting from cooperative or defective moves, we now aim at dissecting
the mechanisms.
We tested whether rats learn to coordinate in a game where coordination with a
conspecific leads to highest number of rewards. We have found that rats learn to
coordinate and that they are not simply following the other rat, since decreasing
the reward for coordinating leads to a significant decrease in coordination.
NEURAL MECHANISMS OF SOCIAL TRANSMISSION OF FEAR IN RATS
This project aims at investigating the mechanisms underlying social transmission
of fear (STF) in rats, i.e. how rats respond to the fear displayed by a
conspecific. In order to unravel the neural circuit underlying STF, we will first
determine how prior self-experience with shock contributes to STF and what
are the sensory cues that mediate this process.
We found that rats do not rely on visual cues, alarm calls or short range chemical
signals to detect fear in a conspecific. Instead, they use auditory cues which are
likely to signal the sudden transition from motion to immobility. Through sound
playback experiments, we found that the absence of movement-evoked sound
was necessary and sufficient to induce fear in rats. In addition we have found that
prior experience with shock is necessary, but not sufficient for vicarious fear.
IGC ANNUAL REPORT ‘11
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53

INFECTION
AND IMMUNITY
Michael Parkhouse Principal Investigator
PhD in Biochemistry, University of London
Head Immunology, Institute Animal Health, Pirbright, UK
Director, Centro Nacional de Biotechnologia, Madrid, Spain
Special Appointment-equivalent to University Professor, National Institute for Medical Research, Mill Hill, London
Principal Investigator at the IGC since 2000
The theme of the group is the reciprocal adaptation between an infectious
organism and its host. The necessity to recognise and destroy invading pathogens
has played a crucial role in the evolution of the immune system of both
vertebrates and invertebrates. At the same time, pathogens, in particular viruses,
have evolved strategies to manipulate the immune system. An efficient
immune system must select the immune effector mechanism most appropriate
to the biology of the pathogen. Thus, the study of how pathogens control immune
responses will offer novel approaches for the manipulation of the immune
responses in health and disease, with novel vaccines and strategies to
downregulate the immune system (e.g. inflammation) being the most obvious
possibilities. Therefore, we are identifying and characterising virus host evasion
genes directed towards subversion of cell biology and innate immunity. The two
viruses that we have selected are Herpesvirus and the African Swine Fever Virus.
EVALUATING AND CONTROLLING THE RISK OF AFRICAN SWINE FEVER (ASF)
IN THE EU
The aim is to provide new tools and strategies for the control of ASF in Africa and
reduce the risk of importation and/or spread of the disease in EU member states.
GROUP MEMBERS
Rute Nascimento (Post-doc, started in July )
Sílvia Correia (Post-doc)
Helena Costa (PhD student)
Sónia Ventura (PhD student)
Emanuel Costa (Research Technician)
COLLABORATORS
Sun Huaichang (College of Veterinary Medicine, Yangzhou University, China)
Alexandre Leitão (Faculdade de Medicina Veterinária, Universidade Técnica
de Lisboa, Portugal)
John Sinclair (University of Cambridge, UK)
Steve Goodbourn (St. George's Hospital, University of London, UK)
FUNDING
Framework Programme 7 (FP7), European Commission
Fundação para a Ciência e a Tecnologia (FCT), Portugal
We produced B602L, p54, A104R and K205R recombinant proteins which have
been used as antigens to field test ASFV isolates in new recombinant ELISAs by
Dr Carmina Gallardo, CISA-INIA. As the K205R protein revealed high IgM titres,
it has been produced and sent to Dr Carmen Vela, INGENASA, to develop a new
commercial kit able to detect recently ASFV infected animals. An additional ASFV
Interferon evasion gene has been identified using luciferase reporter assays.
INHIBITION OF THE RESPONSE OF THE AFRICAN SWINE FEVER VIRUS AGAINST
HOST INTERFERON
Our objective is to determine the mechanisms and consequences of three nonhomologous
host evasion genes (I329L, K205R and A276R) of the economically
important, frequently fatal African Swine Fever Virus (ASFV). All three genes
inhibit a major component of innate immunity, the Interferon (IFN) response,
and may have practical application through the development of novel pharmaceuticals
that manipulate IFN responses and through the construction of an
attenuated gene deletion ASFV vaccine.
We identified the I329L gene as an inhibitor of TLR3 signalling pathway through
targeting of TRIF (Ventura et al. 2012, in prep). The K205R gene was identified
as an interacting partner of STAT2, therefore inhibits the host antiviral response
by inhibiting the expression of interferon stimulating genes (ISGs) (Correia et al
2012, in prep). Definition of their cellular targets and impact on cellular processes
is a necessary step prior to the construction of a deletion mutant virus vaccine.
MECHANISM AND CONSEQUENCES OF AN IL-8 INDUCING HERPESVIRUS GENE
The project builds on our own observations and experience with UL76 gene
from Human Cytomegalovirus (HCMV), a novel virus host evasion gene previously
lacking a function and, with the exception of the herpesviruses, still without
any homologue in the database. The main objective of this project is to define
the mechanisms employed by UL76 to induce IL-8 expression and G2/M cell
cycle arrest. Understanding this virus strategy for manipulating cell division and
stimulating IL-8 expression may be exploitable for the rational control of these
important infections in humans, for example, the construction of attenuated
herpes virus vaccines, and the development of possible novel approaches for
the manipulation of host cell biology in health and disease.
We demonstrated that UL76 induces IL-8 expression through NF-kB activation
using deletion mutants of IL-8 promoter luciferase reporter. The activation of
NF-kB by UL76 is dependent of IKK-beta and the degradation of IKB-alpha proteins.
Moreover, expression of UL76 results in p65 translocation to the nucleus
and in increased binding of p65 to the IL-8 promoter region as shown by chromatin
immunoprecipitation.
IGC ANNUAL REPORT ‘11
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DISEASE
GENETICS
Carlos Penha Gonçalves Principal Investigator
PhD in Immunology, University of Umea, 1999
Full Professor, Universidade de Lisboa, Portugal
Head of Genomics Unit
Principal Investigator at the IGC since 2005
Our scientific interests are concerned with the genetic basis of resistance/susceptibility
to disease with special focus on malaria and diabetes. We aim to
develop research programmes based on the systematic analysis of individual
genetic factors involved in disease resistance/susceptibility, both in humans
and in mouse models. Two diseases are the focus of our work: malaria and
type-1 diabetes (T1D). We aim to investigate the pathogenesis of these diseases
by combining cell and molecular biology methodologies with classical genetics
techniques. In coming years a strong theme in the lab will be deciphering the
role of particular cell types of the innate immune system in:
1. Mediating pathogen-induced pathology (in pregnancy and cerebral malaria);
2. Conferring infection resistance (in malaria liver stage);
3. Shaping the responsiveness to auto-antigens (in T1D).
PREGNANCY-ASSOCIATED MALARIA
Pregnancy-associated malaria (PAM) is a severe clinical complication of P. falciparum
infection threatening the life of the mother and the foetus. Infected red
blood cells (iRBC) adhesion and sequestration in the placenta are the inaugural
events in placental malaria pathology but key investigations on the pathogenesis
mechanisms are not amenable in human placenta. We developed two mouse
models of PAM using Plasmodium berghei ANKA infected BALB/c females enabling
us to follow several lines of investigations:
GROUP MEMBERS
Luciana Moraes (Post-doc)
Nadia Duarte (Post-doc)
Ligia Deus (PhD student)
Joana Corte-Real (PhD student, left in December)
Joana Rodo (PhD student)
Lurdes Duarte (PhD student)
Elizabeth Ball (PhD student)
COLLABORATORS
Lars Hviid (University of Copenhagen, Denmark)
Chris Jansen (Leiden University Medical Center, Netherlands)
Claúdio Marinho (Universidade de São Paulo, Brazil)
Maria Mota (Instituto de Medicina Molecular, Portugal)
Jon Clardy (Harvard Medical School, USA)
Peter Crompton (National Institute of Health, USA)
Taane Clark (London School of Hygiene and Tropical Medicine, UK)
Rosário Sambo (Hospital Pediátrico de Luanda, Angola)
Maria Jesus Trovoada (Centro Nacional de Endemias, S. Tomé e Príncipe)
Dan Holmberg (University of Conpenhagen, Denmark)
Linda Wicker (University of Cambridge, UK)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Calouste Gulbenkian Foundation, Portugal
• We use confocal and two-photon intra-vital microscopy techniques to measure
the dynamics of increased adhesion of PAM parasite to the placenta
tissue, in vivo;
• We are testing the hypothesis that PM is not driven by a systemic condition
but is rather a heterogeneous and localised inflammatory process.
We propose that locally-acting immuno-mediators provided by the foetal tissues
would have a crucial role in recruiting cellular components to the inflammatory
infiltrate.
Two manuscripts summarise the results obtained in 2011:
Intravital placenta imaging reveals microcirculatory impact on sequestration
dynamics and phagocytosis of Plasmodium-infected erythrocytes (Submitted).
Distinct placental malaria patterns caused by Plasmodium berghei-derived
strains that fail to induce cerebral malaria in the C57Bl/6 mouse (Submitted).
PLASMODIUM DEVELOPMENT IN HEPATOCYTES
The Plasmodium liver stage is an appealing target for the development of strategies
to control malaria infection and has been a source of promising candidate
vaccines. During malaria liver stage infection single parasites infect individual
hepatocytes and develop into thousands of merozoites. This developmental
process is largely asymptomatic and not amenable to study in humans, therefore
malaria mouse models are instrumental in revealing parasite and host factors
involved in the establishment of the liver stage infection. We propose to
investigate mouse genetic models where we found alterations of liver parasite
expansion with the aim of identifying host factors that hinder the regulation
and efficiency of Plasmodium development in the liver. For this purpose we will
use an exclusive tool set that includes a significant collection of relevant mouse
strains and parasite mutants as well as our established expertise on mouse primary
hepatocyte cultures and imaging techniques.
IGC ANNUAL REPORT ‘11
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One manuscript summarizes results obtained in 2011:
Fas Signalling and Macrophage-Derived HGF Induce Hepatocyte Apoptosis in
Response to Plasmodium Liver Stage Infection. (Submitted).
MALARIA IMMUNOGENETICS
This project aims to identify genetic and immunological components in clinical
and asymptomatic malaria infections by interrogating human sample collections
from Angola and the Island of Principe.
In the Angola collection malaria cases will be compared will healthy controls and
with relatives to identify genetic variants controlling different clinical forms of
severe malaria. The Island of Principe covers approximately 142 square kilometres
with only about 6000 inhabitants and little emigration. We collected
samples from a total of 1867 healthy individuals in 10 different localities in
Principe in the years 2004, 2005 and 2008. This may represent one of the very
few examples of a whole-population based study in malaria. We found out that
in 2005, while the disease coursed at the mesoendemic level, 20% of the apparently
healthy individuals were infected with Plasmodium. We aim to use this
collection to identify genetic factors that are determining the non-symptomatic
carrier status.
One manuscript summarizes results obtained in 2011:
Involvement of IFNAR1 in cerebral malaria reveals a pathogenesis mechanism
dependent on CD8+ cells (Submitted).
B1 CELLS AND NATURAL ANTIBODIES IN TYPE 1 DIABETES (T1D) PATHOGENESIS
Type-1 diabetes (T1D) is generally known as a T-cell mediated autoimmune disease
where the pancreatic β-cells are destroyed and insulin secretion abrogated.
Yet, B lymphocytes were proven necessary in disease pathogenesis and
the detection of autoantibodies to Beta-cell antigens are one of the earliest indicators
of disease. We propose that autoreactive natural antibodies (NAbs) act
as effector molecules that fuel the autoimmune process through complement
system activation, increased antigen presentation to T cells and/or autoreactive
B cell proliferation in the pancreatic lymph nodes. By exploring on one hand the
involvement of B1 cells and in particular autoreactive NAbs in T1D pathogenesis
and on the other hand the genetic factors determining the dysfunctions in this
cell compartment, we will be able to uncover the missing links. This project will
elucidate mechanisms that link early B1 cell development to autoantibody secretion
and to T1D pathogenesis in murine and human disease.
IGC ANNUAL REPORT ‘11
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COMPUTATIONAL
GENOMICS
José Pereira-Leal Principal Investigator
PhD in Biomedical Sciences, Universidade do Porto, Portugal, 2001
Post-Doc at EMBL European Bioinformatics Institute - Cambridge, UK
Post-doc & Career Development Fellow at MRC Laboratory of Molecular Biology,
Cambridge, UK
Head of Bioinformatics Unit
Principal Investigator at the IGC since 2006
link to external website
We are interested in the evolutionary mechanisms underlying the origins and
evolution of cellular life and the complex structures within the cell, the transitions
to multi-cellularity, and the medical applications of evolutionary genomics.
Our research encompasses themes that are broadly classified as evolutionary
cell biology, systems biology, pathogenomics, and translational or medical
bioinformatics.
EVOLUTIONARY CELL BIOLOGY
The aims of this project are to study the origins of cellular structures, and to
develop the methods and resources that enable evolutionary studies in cell
biology. We have developed three data integration platforms: TrafficDB, CentrioleDB
and SporeDB, where automated methods for sequence classification are
integrated with morphological information, described by image data and novel
controlled vocabularies.
GROUP MEMBERS
Joana Cardoso (Post-doc, started in May)
Pedro Coelho (Post-doc, started in October)
Sofia Braga (PhD student)
Yoan Diekmman (PhD student)
Beatriz Gomes (MSc student, started in October)
Diogo Santos (Research student, started in November)
COLLABORATORS
José Luis Passos Coelho (Instituto Português de Oncologia
Dr. Francisco Gentil, Portugal)
Paula Chaves (Instituto Português de Oncologia Dr. Francisco Gentil,
Portugal)
David Pellman (Harvard Medical School, USA)
Max Loda (Harvard Medical Shool, USA)
Monica Bettencourt-Dias (IGC, Portugal)
PUBLIC ENGAGEMENT IN SCIENCE
Public lecture - AR, Champalimaud Centre for the Unknown, November
In collaboration with the Cell Cycle Regulation laboratory we characterised the
evolutionary pathway of the centriolar duplication machinery using both computational
and experimental approaches (published). We have also discovered
that there is a selective loss of genetic redundancy when bacteria adopt an
obligate intracellular lifestyle, such as chloroplasts and mitochondria (accepted
for publication).
CELL BIOLOGY OF CANCER
Within this project we aim to understand the molecular basis of tumour heterogeneity
and cancer progression.
We are studying the molecular and clinical heterogeneity of breast cancer, and
our preliminary results suggest two distinct entities, driven by different molecules
and processes and with distinct outcomes. Using gene expression data
we have identified novel prognostic markers for breast cancer. We are currently
collaborating with pathologists at Portuguese hospitals to test our computational
predictions by immunohistochemistry in human samples.
IGC ANNUAL REPORT ‘11
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BEHAVIOUR
AND METABOLISM
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Carlos Ribeiro Principal Investigator
PhD in Cell Biology, University of Basel, Basel, Switzerland, 2003
Postdoctoral fellow, Biozentrum, University of Basel, Switzerland
Postdoctoral fellow, Research Institute of Molecular Pathology (IMP)
and Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences, Vienna, Austria
Principal Investigator at the IGC since 2009
link to external website
We are interested in understanding how molecular and cellular mechanisms control
complex biological processes at the level of the whole organism. For this
we are focusing on how the internal metabolic state of the fruit fly Drosophila
melanogaster affects its behavioural decisions. Starting from novel behavioural
paradigms we use molecular genetic techniques to identify and characterise
genes and neuronal populations involved in producing the appropriate behavioural
response to a specific metabolic need of the fly.
MOLECULAR MECHANISMS OF NUTRIENT CHOICE
We want to understand how Drosophila knows what type of nutrients it needs
and which are the molecular mechanisms used by the nervous system to change
the behaviour of the animal to allow it to find and eat the required nutrients.
We have continued investigating how conserved nutrient sensing pathways act
in the nervous system to control feeding. Furthermore, by analysing genes identified
as being required for nutrient choice in a neuronal whole-genome RNAi
screen we are investigating novel molecular mechanisms mediating nutrient homeostasis.
Taken together these studies are providing us with a model and an
entry point for studying nutrient balancing and value-based decision-making at
the molecular level.
GROUP MEMBERS
Laura Napal Belmonte (Post-doc)
Pavel Itskov (Post-doc, started in March)
Ricardo Gonçalves (Post-doc, started in July)
Samantha Herbert (PhD Student)
Veronica Corrales (PhD Student, started in October)
Ana Paula Elias (Lab Manager and Research Assistant)
Célia Modesto Baltazar (Research assistant)
COLLABORATORS
Aldo Faisal (Imperial College London, UK)
Matthew Piper (UCL, London, UK)
Mattias Allenius (Linköping University, Sweden)
FUNDING
Champalimaud Foundation (CF), Portugal
BIAL Foundation, Portugal
NEURONAL MECHANISMS OF NUTRIENT CHOICE
We want to identify and analyse the neuronal networks used by Drosophila
to change the behaviour of the animal to allow it to find and eat the required
nutrients.
We have used genetic approaches to identify neuronal populations which are
required for nutrient choices. Currently we are analysing the identified neuronal
substrates for nutrient homeostasis to understand how these neuronal populations
act to guide feeding decisions.
What type of food should the animal choose?
QUANTITATIVE ANALYSIS OF FEEDING BEHAVIOUR IN DROSOPHILA
In collaboration with the laboratory of Aldo Faisal at Imperial College London
we use automated video analysis to quantitatively link genetics to feeding
behaviour in the fruit fly. These studies are providing us insights into the behavioural
strategies used by the fly to maintain nutrient homeostasis as well as
their biological implementation in the nervous system.
Drosophila adult brain (gold) with specific neuronal subsets marked by GFP (green).
Automatically tracked path of a foraging fly.
IGC ANNUAL REPORT ‘11
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COMPLEX ADAPTIVE
SYSTEMS AND
COMPUTATIONAL BIOLOGY
Luis Mateus Rocha Principal Investigator
PhD in Systems Science, State University of New York, 1997
Postdoctoral Fellow, Los Alamos National Laboratory (NM. USA)
Associate Professor, Indiana University, USA
Principal Investigator at the IGC since 2000
link to external website
We are interested in the informational properties of natural and artificial systems
which enable them to adapt and evolve. This means both producing computational
models of biological systems to understand the evolutionary role of
information, as well as abstracting principles from biology to produce adaptive
information technology. Our current research projects are on complex dynamics
in biological networks (gene regulation, cell signalling, and metabolic networks),
text and literature mining (in proteomics, protein-protein interaction
and pharmokinetics), computational models of RNA editing, artificial immune
systems, genomic multivariate analysis, evolutionary systems, artificial life, cognitive
science, and biosemiotics.
BIOMEDICAL LITERATURE MINING
The aims are to carry out literature-based automatic discovery, classification
and annotation of protein-protein and gene-disease interactions, pharmokinetic
data, protein sequence family and structure prediction, functional annotation
of transcription data, enzyme annotation publications, etc.
We are currently looking at automated mechanisms for document classification
and obtained preliminary results that are being prepared for publication.
This entails close collaborations with Analia Lourenço (Minho) and Hagit Shatkay
(Queens University, Canada).
COLLECTIVE DYNAMICS IN COMPLEX BIOCHEMICAL NETWORKS
Modelling of the dynamics of complex biochemical networks, to identify control,
modularity, robustness and collective computation. Currently working with
models of genetic regulation in yeast, body segmentation in Drosophila, intracellular
signal transduction in fibroblasts, a genome-scale transcriptional and
metabolic network for E. coli, and others.
GROUP MEMBERS
Manuel Marques-Pita (Post-doc)
Artemy Kolchinsky (PhD Student)
Azadeh Nematzadeh (PhD Student)
Tiago Simas (PhD Student)
Alaa Abi-Haidar (PhD Student, left in January)
Santosh Mannika (PhD Student, started in June)
COLLABORATORS
Anália Lourenço (Universidade do Minho, Portugal)
Hagit Shatkay (Queen's University, Canada)
Marta Cascante (University of Barcelona, Spain)
Jim Crutchfield (University of California, Davis, USA)
Santiago Schnell (Michigan University, USA)
Luis Amaral (Northwestern University, USA)
Chistof Teuscher (Portland State University, USA)
Stefan Mass (Lehigh Univeraity, USA)
Alekos Athanasiadis (IGC, Portugal)
Jorge Carneiro (IGC, Portugal)
Pedro Lima (Instituto Superior Técnico, Portugal)
Porfirio Silva (Instituto Superior Técnico, Portugal)
Nuno Crato (Instituto Superior de Economia e Gestão, Portugal)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
FLAD Computational Biology Collaboratorium, Portugal
Uninova collaboration
PUBLIC ENGAGEMENT IN SCIENCE
Manuel Pita, Public lecture - AR, Champalimaud Centre for the Unknown,
November
We have completed the first year of our FCT funded R&D grant on studying collective
information processing in biochemical networks.
COMPUTATIONAL MODELS OF RNA EDITING
We are building computational models to study the evolutionary implications of
genotype editing in the living organisation. Our goal is twofold:
1. To study the role of RNA Editing regulation in the evolutionary process;
2. To investigate the conditions under which genotype edition improves the
optimisation performance of evolutionary algorithms.
After developing a set of computational tools needed for a number of simulations
and studies on artificial RNA editing systems, we are currently generating
and analysing data in the context of our collaborations with Alekos Athanasiadis
(IGC) and Stefan Mas (Lehigh).
ARTIFICIAL MODELS OF T-CELL CROSS-REGULATION
We use Carneiro's Model of Cross-regulation in T-Cell dynamics to produce bioinspired
algorithms for binary classification. The goal is to gain further insights
into T-cell cross-regulation in the vertebrate immune system, and produce useful
bio-inspired algorithms for text mining and spam detection. After one of our
team members 'completion of his PhD on this project, we are currently redefining
the next goals, and approaches for its continuation, as well as preparing
grant applications to hire new team members.
STOCHASTIC MODELS OF TOPOLOGY CONSTRAINTS ON COMPLEX NETWORKS
This project aims to study of transitive properties of complex networks modelled
as weighted graphs. Studying the impact of alternative distance measures
on scale free and small-World behaviour, and developing stochastic
models of vertex aging in networks, to better predict network growth. Ongoing
analysis of large-scale Wikipedia data, networks of neuronal activity, etc.
Started collaboration with Nuno Crato (ISEG) to model decision-tree searches.
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INFLAMMATION
Miguel P. Soares Principal Investigator
PhD in Science, University of Louvain, Belgium, 1995
Research Fellow, Harvard Medical School, Boston, MA, USA
Instructor in Surgery, Harvard Medical School, Boston, MA, USA
Lecturer, Harvard Medical School, Boston, MA, and USA
Invited Professor at Lisbon Medical School, Universidade de Lisboa, Portugal
Head of IGC Histopathology Unit
Principal Investigator at the IGC since 2004
Inflammation is an immediate response to foreign challenge and/or tissue injury
characterised by local and transient extravasation of soluble molecules and leukocytes
from blood into non-lymphoid tissues. While the physiologic purpose
of inflammation is to restore homeostasis there are many instances where inflammation
becomes pathological. Moreover, there is a general consensus that
some of the major causes of human morbidity and mortality are in fact due to
pathological conditions in which inflammation and/or immunity are the underlying
cause of disease. The research effort developed in our laboratory is aimed
at understanding the cellular and molecular mechanisms assuring that in the
overwhelming majority of cases inflammation exerts its physiologic purpose
without becoming pathological. Our body of work supports the notion that one
of such mechanisms relies on the expression of cytoprotective genes that allow
inflammation to progress without causing irreversible tissue damage.
MODULATION OF PROGRAMMED CELL DEATH BY FREE HEME
Under homeostasis, the reactivity of heme prosthetic groups is controlled by
their insertion into the “heme pockets” of hemoproteins. Under oxidative stress
however, some hemoproteins can release their heme prosthetic groups. The
non-protein-bound (free) heme becomes highly cytotoxic, most probably due
to the Fe atom contained within its protoporphyrin IX ring. When this occurs,
free heme can catalyse, in an unfettered manner, the production of free radicals
via Fenton chemistry and sensitise cells to undergo programmed cell death.
In our laboratory we have shown that the cytotoxic effect of free heme plays
an important role in the pathogenesis of a variety of inflammatory diseases in
which hemoproteins release their prosthetic heme groups.
MECHANISMS OF DISEASE TOLERANCE
Malaria, the disease caused by Plasmodium infection, remains one of the main
causes of morbidity/mortality worldwide. Epidemiologically however, less than
1-2% of Plasmodium-infected individuals succumb to severe forms of malaria.
This suggests that Plasmodium has co-evolved with its human host to
reach an evolutionary “trade off” in which infection “rarely” compromises host
viability. This trade off is thought to rely almost exclusively on the ability of the
host’s immune system to control parasite burden, a defence strategy referred
to as resistance to infection. However, there is an additional host defence strategy
that operates during Plasmodium infection and that limits disease severity
irrespectively of parasite burden, i.e. tolerance to infection. The mechanisms
underlying host tolerance to Plasmodium infection remain poorly understood.
We are exploring the hypothesis that several genes that regulate the deleterious
effects of free heme might control host tolerance to infection.
GROUP MEMBERS
Ana Ferreira (Post-doc, left in March)
Josina Filipe (Post-doc, left in January)
Virgínia Oliveira Marques (Post-doc, left in January)
Ana Cunha (Post-doc)
Rafaella Gozzelino (Post-doc)
Susana Ramos (Post-doc, started in February)
Rasmus Larsen (Post-doc)
Zélia Gouveia (External PhD Student)
Andreia Cunha (PhD student)
Nadja Pejanovic (PhD student)
Ivo Marguti (PhD student, left in July)
Bahtiyar Yilmaz (PhD Student)
Sofia Rebelo (Lab Manager)
Sílvia Cardoso (Laboratory Assistant)
COLLABORATORS
Josef Anrather (Cornell University, New York, USA)
Leo Otterbein (Harvard Medical School, Boston, USA)
Ann Smith (University of Missouri - Kansas City, USA)
Ingo Bechmann (Johann Wolfgang Goethe-University, Frankfurt/Main,
Germany)
Yves Beuzard (Hospital Saint Louis, Paris, France)
Lukas Kühn (Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland)
Carlos Penha Gonçalves (IGC, Portugal)
Jocelyne Demengeot (IGC, Portugal)
Henrique Silveira (Instituto de Higiene e Medicina Tropical (IHMT), Portugal)
Salome Gomes (IBMC- Universidaded do Porto, Portugal)
FUNDING
FP6 Framework Programme 6, European Commission
GEMI Fund Linde Healthcare
The Bill & Melinda Gates Foundation, USA
Fundação para a Ciência e a Tecnologia (FCT), Portugal
PROTECTION AGAINST MALARIA BY "NATURAL" ANTIBODIES
We are testing the hypothesis that antibodies directed against a specific carbohydrate
produced by gut pathogens might play a role in immunity against
severe forms of malaria. Newborns and young children, who are most susceptible
to these severe forms of the disease, have not yet built up antibodies to this
carbohydrate. We will assess whether stimulating production of this antibody
after birth can offer increased protection.
REGULATION OF ADAPTIVE IMMUNITY BY HEME OXYGENASE-1 (HO-1)
Over the past few years we extended our original studies to test the hypothesis
that HO-1 might regulate T cell mediated autoimmunity leading to the pathogenesis
of immune mediated inflammatory diseases such as diabetes, arthritis
or multiple sclerosis (MS). We found that this is indeed the case for MS, where
disease progression is caused by T cell driven neuroinflammation, leading to
central nervous system injury. The mechanism underlying the protective effect
of HO-1 against autoimmune neuroinflammation is not clear. We are testing the
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hypothesis that expression of HO-1 by antigen presenting cells, and in particular
by dendritic cells, regulates their immunogenicity in a manner that arrests the
pathogenesis of autoimmune diseases.
ANTI-ATHEROGENIC EFFECT OF HEME OXYGENASE-1: MECHANISM OF ACTION
Expression of HO-1 exerts anti-atherogenic effects that are mediated, at least
in part, by the production of the gasotransmitter carbon monoxide (CO). The
hypothesis tested under this project is that CO can prevent the pathogenesis
of atherosclerosis via a mechanism that involves the modulation of monocyte/
macrophage activation as well as the inhibition of smooth muscle cell (SMC) proliferation.
We have shown that the effect of CO is associated with it's ability to
suppress the pro-inflammatory phenotype of monocyte/macrophage activation
and to block smooth muscle cell (SMC) proliferation via a sequence of events
that requires the activation of the p38 mitogen-activated protein kinases
(MAPK). We aim to investigate whether inhaled CO can be used therapeutically
to suppress the development of lipid-mediated atherosclerosis.
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EVOLUTION
AND DEVELOPMENT
Élio Sucena Principal Investigator
PhD in Evolution and Development, Genetics, Cambridge, UK, 2001
Post-Doc at Princeton University, USA
Post-Doc at University of Western Ontario, Canada
Liaison with the Champalimaud Foundation
Principal Investigator at the IGC since 2003
Research in my lab focuses on evolutionary novelties, defined as a novel body
part that is neither homologous to any body part in the ancestral lineage nor
serially homologous to any other body part of the same organism. This concept
can be extended to other traits, for example, physiological or behavioural.
We have identified several instances of novelty, as defined above, that we are
experimentally dissecting:
1. At the genetic level, looking at gene function evolution upon gene duplication;
2. At the cellular level, approaching immune cell function diversity in Drosophila;
3. At the morphological level by studying the evolutionary origin of dorsal
appendage formation in the Drosophila clade.
DISSECTING THE DEVELOPMENTAL GENETIC BASIS OF EVOLUTIONARY NOVELTY
The eggshell's dorsal appendages are structures unique to the Drosophila lineage,
found throughout the lineage in various numbers, shapes and sizes. With
Adrien Fauré and Claudine Chaouiya we have progressed in the establishment
of a model that recapitulates the epithelial patterning, and with which we are
now able to explore the variation in number this structure displays across Drosophila
species. In addition, our research into eggshell patterning of Ceratitis
capitata, a species without dorsal appendages outside of the Drosophila clade,
has led to a renewed understanding of the role played by the Dpp pathway
during oogenesis. With the combination of these two lines of research we continue
to investigate both the possible origin as well as the diversification of this
evolutionary novelty.
GROUP MEMBERS
Nelson Martins (Post-doc)
Kohtaro Tanaka (Post-doc, started in May)
Alexandre Leitão (PhD student)
Barbara Vreede (PhD student)
Vítor Faria (Research Assistant)
COLLABORATORS
Jen Sheen (Massachusetts General Hospital, USA)
Mark Borowsky (Massachusetts General Hospital, USA)
Brad Chapman (Massachusetts General Hospital, USA)
Ignacio Rubio Somoza, (Max Planck Institute for Developmental Biology,
Germany)
Detlef Weigel (Max Planck Institute for Developmental Biology, Germany)
Pedro L. Rodriguez Egea (Instituto de Biología Molecular y Celular
de Plantas, Universidad Politécnica de Valencia, Spain)
Markus Teige (Max F. Perutz Laboratories, Univ. Vienna, Austria)
Andreas Bachmair (Max F. Perutz Laboratories, Univ. Vienna, Austria)
Claudine Chaouiya (IGC, Portugal)
Adrien Fauré (IGC, Portugal)
Thiago Carvalho (IGC, Portugal)
Jocelyne Demengeot (IGC, Portugal)
Luis Teixeira (IGC, Portugal)
Fernando Roch (Centre de Biologie et Developpement, France)
Sara Magalhães (Faculdade de Ciências, Universidade de Lisboa, Portugal)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Instituto Gulbenkian de Ciência (IGC), Portugal
Comparing the patterning network of Drosophila with a species without dorsal
appendages, the mediterranean fruitfly Ceratitis capitata, has pointed us
toward a key node in the network: the gene mirror. This transcription factor is
absent in Ceratitis oogenesis, but performs a key function in defining the cells
that make up the dorsal appendages, as well as defining the dorso-ventral axis
of the future Drosophila embryo. We are currently exploring this co-option in
more detail.
FUNCTIONAL EVOLUTION UPON GENE DUPLICATION
We have been studying a recently expanded gene family in Drosophila, the
Three Finger Domain Protein (TFDP), in particular the nine genes of clusters III
and V. Given their expression patterns in the Drosophila eye disc, we hypothesise
that, in higher Diptera, TFDP genes have been co-opted by the ancestral
eye development gene network. Different genes of this recently expanded family
have been deployed in specific glial/neural cell subsets as to participate in
the highly dynamic process leading to the formation of both photoreceptor
axonal tracks and their respective myelin sheaths. This study establishes the
TFDP gene family evolution as an example of neo/sub-functionalisation by gene
duplication. Further work will clarify the specific impact of regulatory evolution
over the gene network driving the cellular mechanisms in the developing eye of
holometabolous insects.
In order to have a comprehensive description of expression pattern evolution
of these nine TFDP genes in Drosophila, we extended our analysis to Tribolium,
Anopheles, Megaselia and Ceratitis. With this wide phylogenetic coverage, we have
a clear idea of the duplication history of these genes and hence a strong basis to
define instances of sub- and neo-functionalisation for future promoter dissection.
IMMUNE CELL FUNCTION DIVERSITY IN DROSOPHILA
We had previously shown that, contrary to the current view, Drosophila plasmatocytes
(the functional analogues of vertebrate macrophages) constitute a
heterogeneous population. For this we have established a novel protocol for
PARASITOID WASP EGG SURROUNDED BY HOST IMMUNE CELLS (PLASMATOCYTES).
Heterogeneity of plasmatocyte population is apparent by the differential expression
of green (Cg25C) and red fluorescence (eater).
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hemocyte purification using a combination of GFP lines, specific staining and
FACS analysis. Recently, we have shown that immune challenge leads to changes
in total cell number and subset proportions. Moreover, using G-trace technique,
we have determined that such changes are not due to shifts in cell identity but
rather the result of differential proliferation and/or recruitment.
We have now found new plasmatocyte subsets and shown that some of these
subsets change dynamically during larval development. After confirming the
long standing hypothesis that hemocytes are essential to resist parasitoid egg
infections we have described the plasmatocyte heterogeneity during this immune
response. The results show that there is a dynamic change in all plasmatocyte
subsets during the immune response while they maintain the expression of
a differentiated plasmatocyte marker.
EVOLUTION OF Drosophila melanogaster IMMUNE RESPONSE
The mechanistic basis of the immune response in Drosophila has been widely
studied; however, little is known about the evolutionary and physiological
mechanisms that drive local adaptation to pathogens. It is also unknown if this
adaptation is dependent on factors such as the infected life-stage, route of infection,
pathogen type or multiple infections, and the associated trade-offs. Using
experimental evolution in Drosophila, to different and contrasting immune challenges,
we have established the grounds to address these questions and gain
insights about the genes and mechanisms involved in adaption to pathogens.
We have imposed 20 generations of experimental evolution in Drosophila under
different immune challenges. These replicate populations have adapted to
contrasting conditions and perform significantly better that controls. We are
currently testing for the establishment of trade-offs and will pursue the genetic
basis of this adaptation.
Cages containing Drosophila populations undergoing experimental evolution.
Phylogenetic relationships between different dipterans used in the lab to study
the origin and diversification of egg dorsal appendages (right panels).
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HOST
MICROORGANISM
INTERACTIONS
Luis Teixeira Principal Investigator
PhD in Biomedical Sciences, Faculdade de Medicina da Universidade de Lisboa, 2005
Postdoctoral Fellow, Cambridge University, UK
Principal Investigator at the IGC since 2009
Multicellular organisms and microorganisms are continuously interacting. Many
of these interactions are mutually beneficial. However, multicellular organisms
have to actively thwart invasion by pathogenic microbes. We are studying the
interaction of the model organism Drosophila melanogaster with different microorganisms,
in particular intracellular ones. Recently it has been shown that
there are conserved innate immunity pathways against viruses, between insects
and mammals. We are investigating mechanisms of resistance to viruses in the
fruit fly. Interestingly, we have found that the intracellular bacteria Wolbachia
confer resistance to RNA viruses in D. melanogaster. We want to understand
the molecular basis of this induced resistance. Finally, we are interested in the
interplay between Drosophila and Wolbachia itself, at the molecular level, in
particular how the host controls Wolbachia or Wolbachia manipulates the host.
IDENTIFICATION AND CHARACTERISATION OF GENES INVOLVED
IN DROSOPHILA-WOLBACHIA INTERACTIONS
This project aims at studying the interaction between the genetic model organism
Drosophila melanogaster, and one of the most widespread intracellular
bacteria known: Wolbachia. Wolbachia are vertically transmitted, obligatory
intracellular proteobacteria that infect a wide range of arthropods and filarial
nematodes. Very little is known of the Wolbachia-host interaction at the cellular
or molecular level. We propose here to identify and characterize genes of
D. melanogaster and Wolbachia involved in this interaction through a genetic
screen. We will also identify Wolbachia genes that interact with the host. Many
intracellular bacteria manipulate the host through the secretion of effector proteins
into the host's cells. We will express candidate effector proteins in uninfected
Drosophila cells in order to test the induction of a panel of phenotypes
in these cells. Positive hits will be considered bona fide effector proteins and
further characterised.
ANALYSIS OF WOLBACHIA PROTECTION AGAINST VIRUSES
IN Drosophila melanogaster
The intracellular bacteria Wolbachia protects Drosophila melanogaster against
viral infections. The presence of Wolbachia greatly increases the survival of flies
infected with Drosophila C virus (DCV) and Flock house virus. However, it only
affects the titres of DCV. We will extend this analysis by studying the interaction
with a larger panel of viruses. By identifying to which kind of viruses Wolbachia
increases resistance we will gain insight into the mechanism of protection.
We will also test the induction of viral resistance by different strains of Wolbachia.
The purpose is to find how much variation exists in this phenotype and
if this variation is correlated with other characteristics of the tested Wolbachia
strains. Finally, an important unresolved question is if the induced protection
is cell-autonomous. We will test if Wolbachia protection to viruses extends to
Drosophila cells in culture and address this question.
GROUP MEMBERS
Álvaro Gil Ferreira (Post-doc)
Catarina Carmo (Post-doc)
Ewa Chrostek (PhD Student, started in April)
Inês Pais (Master student, left in October)
Joana Pereira (Technician, started in October)
Marta Marialva (Technician, left in October)
Sara Esteves (Technician, left in October)
COLLABORATORS
Alain Kohl (University of Cambridge, UK)
Élio Sucena (IGC, Portugal)
Gabriela Gomes (IGC, Portugal)
Karina Xavier (IGC, Portugal)
Francis Jiggins (University of Cambridge, UK)
Sara Magalhães (Faculdade de Ciências, Universidade de Lisboa, Portugal)
PUBLIC ENGAGEMENT IN SCIENCE
Talk for school students - Grémio de Instrução Liberal de Campo
de Ourique (April)
Practical class on Morgan’s experiments with Drosophila, Escola Secundária
Stuart de Carvalhais, Massamá (November)
HMI DROSOPHILA MICROBIOTA
Bacteria from Drosophila microbiota growing on an agar plate.
We have one manuscript in preparation concerning the lack of Wolbachia protection
to Sigma virus, a negative single strand RNA virus. This negative result
indicates that Wolbachia only protects against positive single strand RNA viruses.
We have also found differences in protection to viruses by different wMel
substrains. We are concluding experiments in order to complete the manuscript.
WOLBACHIA AS A DEFENSE AGAINST RNA VIRUSES IN INSECTS
The bacterial symbiont Wolbachia can make insects resistant to viral infection
and prevent them from transmitting disease. The aim of this project is to understand
this effect, by investigating how Wolbachia causes viral resistance using
the tools of virology, molecular and evolutionary genetics. Our results will be
important for attempts to use Wolbachia to prevent disease transmission in
natural populations.
GUT VIRUS
Drosophila adult gut infected with Drosophila C virus (Actin in red, DNA in blue,
and virus in green).
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EVOLUTIONARY
GENETICS
Henrique Teotónio Principal Investigator
PhD in Evolutionary Genetics, Universidade de Lisboa, Portugal, 2000
Postdoc, Princeton University
Postdoc, University of Oregon Eugene
Principal Investigator at the IGC since 2003
The study of natural selection and its consequences are central to any understanding
of biology because they provide a framework for the origin, divergence
and maintenance of diversity. We are specifically investigating how the
interactions between mating between individuals and meiotic recombination
determine the evolution of polygenic phenotypes. For this we use populations
of C. elegans with standing diversity and alternative mating systems in demographic
conditions defined by discrete non-overlapping generations at constant
high population sizes. We then manipulate the frequency of environmental
change and follow the evolution of phenotypes and genotypes in real time.
Analysis of data involves computer simulations of experimental evolution under
several selection scenarios.
THE INFLUENCE OF MATING, RECOMBINATION AND NATURAL SELECTION
IN C. elegans EXPERIMENTAL EVOLUTION
Understanding adaptation following an environmental shift is necessary to
explain the evolution of biological diversity. The mechanisms thought to limit
diversity mating among related individuals because they cause inbreeding, meiotic
recombination because they determine extent of gametic linkage among
loci, and the degree of dominance or epistatic gene interactions because they
define natural selection. We aim to resolve the influence of these mechanisms
on the adaptation of large populations by employing an experimental evolution
approach in the androdioecious nematode Caenorhabditis elegans under
varying levels of outcrossing rates, initial standing genetic variation and frequency
of environmental change. During experimental evolution several levels
of structural organization, from fitness-proxy and life history phenotypes to
genome wide RNA expression are characterized in their genetic and environmental
components.
GROUP MEMBERS
Ivo Chelo (Post-doc)
Yoannis Theologidis (Post-doc)
Peter Sandner (Post-doc, started in June)
Sara Carvalho (PhD student)
Bruno Afonso (PhD student)
Christine Goy (Lab Manager)
Judit Nedli (Technician, started in September)
COLLABORATORS
Matt Rockman (New York University, USA)
Boris Shraiman (University of California, Santa Barbara, USA)
FUNDING
European Research Council (ERC), European Commission
Human Frontiers Science Programme (HFSP)
PUBLIC ENGAGEMENT IN SCIENCE
Radio Interview, February
The project also includes hitchhiking mapping of relevant loci, by whole
genome linkage disequilibrium (LD) association mapping and computer simulations
of directional and balancing selection during experimental evolution.
We have completed the characterization of >350 SNPs in experimentally evolved
populations and the characterization of reproduction and viability under several
osmotic and anoxic environmental stress conditions.
ROLE OF GENETIC INTERACTIONS AND RECOMBINATION IN EXPERIMENTAL
EVOLUTION OF C. elegans
Adaptation from standing genetic variation is central to the evolution of phenotypes,
yet its dependence on the molecular details that connect genotype,
phenotype, and fitness is a major unsolved problem in genetics. The effect of
recombination, in particular, is expected to depend on the extent of genetic
interaction among alleles. We propose a multidisciplinary investigation of the
roles of recombination and genetic interactions. We will study laboratory adaptation
of C. elegans populations that start with high genetic variability and are
engineered to have different rates of inbreeding and outcrossing. The project
integrates experimentally determined genome-wide genotype distributions,
multidimensional phenotype (gene expression) measurements, and fitness data
across 100 generations of laboratory populations that differ in their rates of
outcrossing. This integration forms the empirical test bed for theoretical models
of the role of genomic architecture in adaptation.
We will test the predicted positive correlation among non-additive genetic
effects and levels of linkage disequilibrium across the genome. The derivation
of three ancestral populations for experimental evolution with exclusive selfing,
mixed selfing and outcrossing and obligatory outcrossing has been achieved,
as well as derivation of recombinant inbred lines from population at genetic
equilibrium.
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INNATE
BEHAVIOUR
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Maria Luísa Vasconcelos Principal Investigator
PhD in Developmental Neurobiology, Universidade Nova de Lisboa, Portugal, 2004
Principal Investigator at the IGC since 2008
link to external website
Animals exhibit behavioural repertoires that are often innate and result in stereotyped
sexual and social responses to their environment. Innate behaviours
do not require learning or experience and are likely to reflect the activation of
developmentally programmed neural circuits. We are interested in the nature of
defined neural circuits: how activation of circuits elicits specific behaviours. In
complex organisms it has been extremely difficult to study a circuit beyond the
early stages of sensory processing. Drosophila melanogaster is an attractive
model system to understand a circuit because flies exhibit complex behaviours
that are controlled by a nervous system that is numerically five orders of magnitude
simpler than that of vertebrates. We use a combined behavioural, genetic,
imaging and electrophysiological approach to determine how defined neural
circuits and their activation elicit specific behaviours.
FEMALE RECEPTIVITY
Genetic studies have elucidated how Drosophila male courtship behaviour is
specified and its circuit components are being dissected at a surprising speed.
The circuit of female behaviour, on the other hand, has been largely uncharacterised.
We use a behavioural protocol that allows us to selectively inactivate
subsets of neurons in the adult flies only. We use this behavioural approach and
combine it with anatomical and functional dissection of the circuit.
GROUP MEMBERS
Márcia Aranha (Post-doc, started in February)
Nélia Varela (Post-doc)
Ricardo Neto (Post-doc, left in November)
Dennis Herrmann (PhD Student)
Nuno Martins (Masters Student, left in July)
Joao Afonso (Research Technician, left in September)
Sophie Dias (Research Technician)
FUNDING
FP7 - Marie Curie Re-integration Grant, European Commission
Fundação para a Ciência e Tecnologia (FCT), Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Talk at the “biolunch” organised by the biology students of Instituto
Superior de Agronomia, Lisbon (October)
Interview for TVI, Lisbon (October)
A
B
We explored the involvement of apterous neurons (ANs) in receptivity further.
We verified that locomotion is unaffected, as well as the fly’s attractiveness. We
characterised the pattern of ANs. We masculinised the neurons and saw no phenotype,
indicating that ANs are not sexually dimorphic. We have tested females
that have inhibited ANs for their egg laying. Egg laying in virgins is unchanged
indicating that there is not an activation of the postmating switch, at least to
the full extent.
ACROSS SPECIES STRESS ODOUR RESPONSE
Stressed Drosophila melanogaster release an aversive odorant that elicits a robust
avoidance response in test flies. Our data indicate that stress odour avoidance
is not common to all Drosophilids. This behavioural difference between
melanogaster and some of its sister-species provides a powerful framework,
amenable to genetic, developmental and anatomical dissection, to investigate
how evolution has shaped distinct responses to an environmental cue.
We have traced the neurons that innervate the v glomerulus. We observed three
projection neurons connect solely with the lateral horn and one projection neuron
that connects additionally to the Mushroom Body. This result suggests that
the CO 2
response can be modulated.
We tested the response of seven Drosophilidae to CO 2
. We observe a salt and
pepper variation across the phylogenetic tree indicating multiple occurrences
for gain/loss of behaviour.
C
D
PHOTOACTIVATION ALLOWS VISUALISATION OF THE NEURONS INNERVATING THE
V GLOMERULUS.
A - Before photactivation. B - After photoactivation. C - Schematic generated by
automated filament tracing. D - schematic of the projection neuron that connect
to lateral horn and mushroom bodies.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
66

BACTERIAL
SIGNALLING
Karina B. Xavier Principal Investigator
PhD in Biochemistry, Universidade Nova de Lisboa, 1999
Research Scientist, Princeton University, USA
Principal Investigator at the IGC since 2006
Bacteria use small molecules called autoinducers to communicate with one another
by a process called quorum sensing. This process enables bacteria to regulate
behaviours which are only productive when many bacteria act as a group,
similarly to multi-cellular organisms. Behaviours regulated by quorum sensing
are often crucial for successful bacterial-host relationships whether symbiotic
or pathogenic. We use an integrative approach, from molecules to circuits, to
understand the role of quorum sensing in bacterial behaviours. Our research
involves elucidation of the molecules used as signals, the network components
involved in detecting the signals and processing information inside individual
cells, and characterisation of the behaviour of the bacterial community in multispecies
bacterial consortia. We aim to determine the role of cell-cell communication
in multispecies consortia such as the microbiota of the mammalian gut, a
community of great importance to human health.
INTER-SPECIES CELL-CELL SIGNALLING:
ITS ROLE IN BACTERIA CONSORTIA
This project will start in 2012.
GROUP MEMBERS
Jessica Thompson (Post-doc, started in April)
Pol Nadal (Post-Doc, started in February)
Catarina S. Pereira (PhD student)
Rita Valente (PhD student)
Paulo J. Correia (Trainee)
COLLABORATORS
Isabel Gordo (IGC Portugal)
Jocelyne Demengeot (IGC, Portugal)
Stephan Miller (Swarthmore College, USA)
Rita Ventura (ITQB, Portugal)
FUNDING
Howard Hughes Medical Institute (HHMI), USA
Fundação para a Ciência e a Tecnologia (FCT), Portugal
PUBLIC ENGAGEMENT IN SCIENCE
TV interview for science & technology series
In this project we will use an integrated approach towards the characterisation
of the molecular mechanisms involved in inter-species cell-cell communication
and its role in bacterial-host interactions. Our approach is composed of three
specific aims:
1. Characterisation of the molecular mechanisms involved in the regulation of
sensing and response to AI-2, the best studied interspecies signal, in the
model bacteria Escherichia coli;
2. Identification of novel inter-species signals. There is substantial evidence
of additional signals mediating interspecies quorum sensing in
γ-proteobacteria but the molecules remain unidentified;
3. Study of AI-2 signalling directly in vivo. We propose to extend our approaches
to study interspecies interactions directly in the gut of mice.
This work can lead to the rational development of novel therapies that specifically
target inter-species quorum sensing to control complex bacterial communities.
INHIBITION OF BACTERIAL PLANT VIRULENCE BY INTERFERENCE
WITH INTERSPECIES CELL-CELL COMMUNICATION.
In Erwinia carotovora virulence is regulated by non-species specific signal that
foster interspecies communication. In this project we aim to identify receptor
protein(s) and the molecular components of signal transduction involved in recognition
and response to interspecies signals. We will study how these mechanisms
influence gene expression in Erwinia carotovora to determine its impact
in virulence using the potato tuber infectious assay. These bacteria can persist
in the Drosophila gut and induce inflammation. We are studying the effect of
mutants impaired in interspecies communication in Erwinia-Drosophila interactions
in the presence or absence of other bacterial species. We hypothesise that
Erwinia uses Drosophila as a vector for infection and that interspecies communication
has an important role in this process.
We have performed a genetic screen for mutants impaired in regulation of virulence
factors mediated by interspecies signals. We are analysing these mutants
to identify a new signal involved in interspecies communication and also to
determine the impact of these mutants in the production of virulence factors
involved in the pathogenesis of Erwinia towards fruits and legumes but also
during the interaction between Erwinia and Drosophila.
COLONIES OF XENORHABDUS SPP. A PROTEOBACTERIA.
This bacteria undergoes a complex life cycle that involves a symbiotic stage, in
which the bacteria are carried in the gut of the nematodes, and a pathogenic
stage, in which susceptible insect prey are killed by the combined action of the
nematode and the bacteria.
IGC ANNUAL REPORT ‘11
RESEARCH GROUPS
67

RESEARCH
FELLOWS
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
68

BIOPHYSICS
AND GENETICS
OF MORPHOGENESIS
Filipa Alves Research Fellow
PhD in Physics, Universidade Técnica de Lisboa - Instituto Superior Técnico, 2006
Post-doctoral fellow, IGC (Plant Development Group), Portugal
Research Fellow at the IGC since 2011
We are interested in understanding the biophysical and genetic bases of pattern
formation and morphogenesis, from the developmental and the evolutionary
points of view.
Our research is focused on the interplay between the biophysical mechanisms
underlying cell and tissue morphogenesis and the different functional levels of
regulatory networks (e.g. genetic, metabolic, ionic). We are especially interested
in how this interplay both generates and constrains the phenotypic variation
observed within and among species.
GROUP MEMBERS
Pedro dos Santos Lopes (External Masters student)
COLLABORATORS
Jaap Kaandorp (University of Amsterdam, The Netherlands)
Johannes Jaeger (Centre de Regulación Genòmica (CRG), Barcelona, Spain)
Patricia Beldade (IGC, Portugal)
José Feijó (IGC, Portugal)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
FP7 ERA-NET program Complexity-NET, European Commission
We address these questions by using a multilevel modelling approach developed
in close relation with the experimental data. Our theoretical models are mainly
used to formulate organised hypotheses and make testable predictions. As their
calibration and validation are strongly dependent on quantifying and estimating
the biological parameters involved, we also focus part of our work on developing
image analysis tools, databases and parameter optimisation algorithms.
SINGLE CELL MORPHOGENESIS:
MODELLING THE BIOPHYSICS OF CELL POLARISATION
Together with the Cell Biophysics and Development group we are using the germinating
pollen as a model system to study the regulatory interactions linking
ion dynamics, cell polarisation and subsequent pollen tube growth and chemotropic
spatial orientation.
Based on the available experimental data, we are using partial differential equations
to build 3D computational models integrating the cell’s geometry with measured
and calculated ion fluxes, sub-cellular localisation of the main active transporters
and respective molecular kinetics. As most equations in our models do not have
analytical solutions (nor simple numerical ones), we are developing a new numerical
analysis framework to implement this type of computational models.
Our models predict the observed intracellular ion gradients and show their
dependence on other biophysical parameters, shedding light on the minimal
necessary conditions to establish the cell’s polarity axis and providing some
rationales for species-specific differences.
For lily and tobacco pollen tubes, we showed that the observed H+ and Ca2+
gradients are determined by the localisation and activity of their main active
transporters. The rate of Ca2+ sequestration is also critical in shaping its gradient.
When comparing the two species, the distinct H+ and Ca2+ gradients
observed are strongly related to the different fluxes magnitude and cell sizes,
although for Ca2+ the spatial organisation of the intracellular compartments
may also play an important role.
TISSUE AND EMBRYO PATTERNING:
MODELLING GENE REGULATION IN DEVELOPMENT AND EVOLUTION
With the Variation: Development and Selection group, we are studying the formation
of pigmentation patterns in butterfly wings, exploring how the generation
of phenotypic variation may depend on the underlying gene network
topology and respective biophysical and regulatory parameters.
A
C
B
D
We are using theoretical modelling to test different possible network topologies
and candidate genes. We define the gene regulatory networks using partial
differential equations and represent the spatial gene expression patterns in 2D
using finite differences methods. Furthermore, we are developing image analysis
algorithms to quantify and classify the experimental images, and implementing
optimisation methods to estimate the models' parameter values.
MODELLING THE BIOPHYSICS OF CELL POLARISATION.
A - Polarised distribution of the main ion fluxes in pollen tubes. B - The cell is
represented by a composition of geometrical objects. C - Experimental pH and Ca2+
gradients in Nicotiana tabacum. D - Examples of results from the theoretical models.
IGC ANNUAL REPORT ‘11
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Our results provide some testable hypotheses for how the observed variation
on the pigmentation patterns may depend on subtle changes on specific biophysical
parameters, opening interesting perspectives to understand the evolution
of these mechanisms.
We are performing detailed systematic analysis of gene expression and pigmentation
images for B. anynana. With these quantitative data, we are implementing
a classification system for wild-type and mutant phenotypes and also calibrating
the theoretical models. The preliminary results suggest that the eyespot
size is regulated by the shape and amplitude of the morphogen concentration
gradient, while the eyespot colour composition is regulated by gene-specific
network regulatory parameters.
A
C
B
D
MODELLING GENE REGULATION IN DEVELOPMENT AND EVOLUTION.
A - Bicyclus anynana. B - Results from the theoretical models. Image analysis of C
adult pigmentation and D gene expression patterns.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
70

PLANT
GENOMICS
Jörg Becker Research Fellow
PhD in Biology, University of Bielefeld, Germany, 2001
Post-doc, IGC, Portugal
Head of IGC Gene Expression Unit
Research Fellow at the IGC since 2008
Our group is interested in the mechanisms underlying sexual reproduction and
early embryogenesis with a particular focus on the role of the male gametes.
Recent studies have shown that male gametes both in the plant and animal
kingdom carry complex sets of RNA molecules, including not only mRNAs but
also small RNAs. We are particularly interested in the role of these two RNA
classes before, during and after double fertilisation as it occurs in higher plants.
Using Arabidopsis thaliana as our primary experimental model we are addressing
specific questions like:
1. What are the functions of small RNA and DNA methylation pathways in
sperm cells?
2. Do sperm cell-derived RNAs play a role after fertilisation?
3. Do conserved core sets of genetic modules underlie common characteristics
of male gametes across kingdoms?
In addition we are interested in identifying gamete-expressed proteins with
functions in signalling events assuring double fertilisation and initiation of embryogenesis.
GROUP MEMBERS
Leonor Boavida (Post-doc)
Filipe Borges (External PhD student)
Patrícia Pereira (External PhD student)
Marcela Coronado (External PhD student, started in February)
Francisco Sousa (Trainee, started in June)
COLLABORATORS
Rob Martienssen (Cold Spring Harbor Laboratory, USA)
Keith Slotkin (Ohio State University, USA)
Ignacio Rubio Somoza (Max Planck Institute for Developmental Biology,
Germany)
Rui Gardner (IGC, Portugal)
José Feijó (IGC, Portugal)
Ji He (The Samuel Roberts Noble Foundation, USA)
Carlos Plancha (Cemeare Lda, Portugal)
Sheila McCormick (US Department of Agriculture/Agricultural Research
Service, USA)
Liam Dolan (Department of Plant Sciences; University of Oxford, England)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
FP7 Marie Curie International Reintegration Grant, European Commission
FP7 Marie Curie Action: "Networks for Initial Training", European Commission
THE ROLE OF SPERM DERIVED microRNAs DURING DOUBLE FERTILISATION
IN ARABIDOPSIS
The world’s current food supplies rely almost exclusively on double fertilisation
as found in higher plants and characterised by the fusion of two male gametes
(sperm cells) with two female gametes (egg cell and central cell), giving rise
to the embryo and the endosperm. Thus a better molecular understanding of
double fertilisation will eventually provide the tools to improve crops. Micro-
RNAs (MiRs), as essential regulators in development processes and hormone
responses, are likely to play a role in sexual reproduction. Our deep sequencing
data of small RNAs from Arabidopsis sperm cells and pollen indicate that these
express MiRs belonging to dozens of microRNA families, with a number of them
showing higher expression levels in sperm cells than in pollen. We are analysing
the role these sperm cell MiRs might play for sperm cell viability and, if being
delivered to the female gametes upon fertilisation, for the regulation of early
embryogenesis and endosperm development.
We continued to address the potential role of MiRNAs in sperm cells using target
mimics and global inhibitors of small RNA pathways. Moreover, using a novel
FACS protocol (manuscript in prep), we isolated Arabidopsis microspores as well
as vegetative nuclei and sperm cells from mature pollen. By deep sequencing
of bisulphite converted genomic DNA from these three sample types we gained
important new insights into epigenetic changes occurring during microgametogenesis
(manuscript in prep).
IDENTIFICATION OF CONSERVED GERM CELL SPECIFIC MODULES
AS POTENTIAL PRECURSORS OF TOTIPOTENCY
Germ cell differentiation gave rise to all sexually reproducing organisms, but
along their evolution, several species developed distinct spatial and temporal
control over germline proliferation. The gametes are the end products of the
germ cell lineage, and transfer ultimately to the zygote their unique totipotent
potential, capable of giving rise to an entirely new organism. Despite the variety
of mechanisms distinguishing germ cell differentiation and fertilisation strategies
in plants and animals, the molecular pathways towards totipotency are
likely to remain conserved in form of a core set of genetic modules underlying
the totipotent potential of the gametes. This project focuses on the identification
of this conserved core set through the functional analysis of transcripts
encoding orthologue gene products in male gametes of plant, human and fly.
TRANSGENIC ARABIDOPSIS EXPRESSING GAMETE-SPECIFIC TETRASPANINS.
Upper panel - GFP localisation in the plasma membrane of sperm cells (sperm
nuclei mRFP). Bottom panel - Detail of GFP localisation in plasma membrane of
female gametophytic cells: egg cell (right) and synergid cells (left).
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
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During the second year of the project we were able to identify a set of 237 conserved
orthologue gene products that are expressed in the male gametes of the
three species. These products, by encoding both for evolutionarily-conserved
germline regulators and for general housekeeping functions, represented the
starting point for the subsequent selection of 32 genes belonging to a putative
core set of germline determinants. These candidates genes are currently being
characterised in Drosophila.
MOLECULAR AND FUNCTIONAL CHARACTERISATION OF SPERM-EXPRESSED
PROTEINS WITH POTENTIAL FUSOGENIC ROLES DURING DOUBLE
FERTILISATION IN Arabidopsis thaliana
Sexual reproduction is a fundamental biological process common among eukaryotes.
In flowering plants, fertilisation involves a double fusion event between
two male and two distinct female gametes. The signalling interactions involved
in these two independent fusion events are still poorly understood and the
molecular effectors mostly unknown. The project aims to identify the central
protagonists of these cellular interactions, i.e. proteins preferentially localised
to the surface of gametes exhibiting a function that is required for cell-cell adhesion
or fusion. Ultimately we expect to answer some fundamental questions
underlying gamete fusion: How do sperm and egg cell recognise each other and
fuse? Is there any specificity in the two different cell-cell fusion events? Are the
proteins involved specific to cell-cell fusion? And what is the interplay, if any,
between these proteins and the downstream signalling events leading to the
successful production of a seed?
Transgenic Arabidopsis pollen grains expressing H2B-mRFP in the vegetative cell
nucleus (red) and MGH3-eGFP specifically localised to the sperm cell nuclei (green)
allow their co-purification by FACS.
We are currently focused on the functional analysis of two sperm-expressed
tetraspanins and in the identification of partner molecules on male and female
gametes.
PLANTORIGINS
The Marie Curie ITN “PLANT developmental biology: Discovering the ORIGINS of
form” aims to integrate new discoveries and approaches in the fields of plant
morphology, systematics, and developmental genetics with the overall goal of
understanding how the major tissues and organ systems of plants evolved and
what their genetic regulatory basis is. We are focusing on the identification of
conserved networks functioning in sperm cells to assure correct development
and viability of this unique cell type, using a comparative transcriptomics approach
comparing gene expression in male gametes of the angiosperm Arabidopsis
thaliana and the bryophyte Physcomitrella patens. Candidate genes
within the most promising conserved modules will be selected for functional
characterization in Arabidopsis and Physcomitrella. This should ultimately allow
a better understanding of the evolution of regulatory modules underlying
sperm development, viability and fertilisation in the plant lineage.
During 2011 we have established the moss Physcomitrella patens as a model system
in our lab. Subsequently we have developed a collection method for sperm
cells (antherozoids) and archegonia from Physcomitrella based on micromanipulation
that will allow us to analyse the transcriptome by microarray analysis.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
72

NETWORK
MODELLING
Claudine Chaouiya Research Fellow
PhD in Computer Science, Université de Nice Sophie Antipolis, 1992
Assistant professor - Research Associate, Université Aix-Marseille II, France
Research Fellow at the IGC since 2009
link to external website
Major breakthroughs in molecular biology, genomics and functional genomics
allow the delineation of ever-larger interaction networks controlling cellular
processes. To assess the complex behaviours induced by these networks, dedicated
mathematical and computational tools are crucial. In this context, our
major goal is to develop generic and efficient means for the qualitative modelling
and analysis of regulatory networks involving hundreds of components and
diverse regulatory interactions, including inter-cellular signalling. Our strategy
is threefold:
1. Define formal methods to assess dynamical properties of regulatory network
discrete models;
2. Implement these methods either in GINsim (our software dedicated to the
logical modelling of regulatory networks), or in standalone programmes;
3. In collaboration with biologists, challenge our methodological developments
with real case applications, specifying and analysing models for the control
of cell proliferation and differentiation.
GROUP MEMBERS
Pedro T. Monteiro (Postdoc, started in April)
Nuno D. Mendes (Postdoc, started in July)
John Alexander (Technician, from April to November)
COLLABORATORS
Elisabeth Remy (Institut e Mathématiques de Luminy, France)
FUNDING
Fundação para a Ciência e Tecnologia (FCT), Portugal
French National Research Agency, France
MALIN: Modular modelling and Analysis of Large biological Interacting networks
Until recently, most mathematical models for concrete molecular networks have
been defined as a unique whole, considering networks of a limited size. This
approach is not scalable and has to be modified as networks increase in size
and complexity. The goal of this project is to develop efficient computational
methods to represent and analyse qualitative behaviours of large regulatory
networks, particularly in the context of multi-cellular systems. For this, we aim
at defining an appropriate compositional modelling framework. Importantly, the
computational developments envisioned in this project will be confronted and
validated with two challenging concrete biological case studies. The first application
relates to the dorsal appendage morphogenesis in the Drosophila egg,
where cells communicate within a structured topology. The second case study
considers circulating peripheral immune cells and deals with a comprehensive
model for T lymphocytes differentiation.
Work on this project led, in 2011, to a publication:
(B. Luna, C. Chaouiya (2011) Adv Int and Soft Comp Vol 93: 293-302.), a further
manuscript in press (P. T. Monteiro, C. Chaouiya (in press) Efficient verification
for logical models of regulatory networks. Adv Int and Soft Comp Vol 154).
And two more in preparation:
(N. D. Mendes et al. Composition and abstraction of iterated logical regulatory
modules using process algebras; A. Fauré et al. Dorsal patterning of the Drosophila
eggshell).
CALAMAR: COMPOSITIONAL MODELLING AND ANALYSIS OF LARGE MOLECULAR
REGULATORY NETWORKS - APPLICATION TO THE CONTROL OF HUMAN CELL
PROLIFERATION
Appropriate tools for the dynamical modelling, analysis and simulation are
required to delineate the functioning of regulatory networks. In this context,
different formalisms can be considered, from logical (qualitative) models to differential
(quantitative) models. This project intends to develop novel methods
to efficiently represent and analyse the behaviour of large regulatory networks.
This challenge will be addressed through the conception of computational
methods for network reduction and (de)composition (yet keeping track
of essential dynamical properties). Formal relationships between qualitative and
quantitative models will be generated by the application of dedicated abstraction
techniques. These generic methods will be confronted with a reference
application, namely the analysis of a comprehensive map of the RB/E2F regulatory
network, which plays a key role in the control of human cell proliferation.
In 2011, work on this project led to manuscripts in preparation: Calzone et al.
Mathematical Approach to account for alterations in bladder tumours, and Bereguier
et al. Dynamical analysis of logical models using compressed hierarchical
state transition graphs.
GINsim screenshot displaying the logical, integrated model of the regulatory network
and signalling pathways controlling Th cell differentiation (Naldi et al. PLoS
Comput Biol 6(9): e1000912, 2010).
Directed graph accounting for the plasticity of cell subtypes: arrows between cell
lineages denote switches elicited by the corresponding environment.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
73

LUPUS
AND AUTOREACTIVE
IMMUNE REPERTOIRES
Constantin Fesel Research Fellow
PhD in Immunology, Université Paris VI, 1998
Post-doctoral Fellow, Weizmann Institute of Science, Rehovot
Principal Investigator at the IGC since 2001
While the detection of molecular mechanisms as well as of genetic disease risk
factors rapidly evolves, the systemic diversification of specificity repertoires is
still badly understood. In this situation, it is increasingly relevant to model the
pathogenetic process that leads to autoimmune diseases as a whole, since they
are known to depend on complex interactions of molecular and cellular mechanisms.
Systemic Lupus Erythematosis (SLE) is a human autoimmune disorder
where altered physiologies and self-reactive repertoires of both B- and T-cells
are intimately connected. Our approach is to model, in a stepwise fashion, the
ways in which genetic factors and molecular mechanisms are interconnected.
Since we found particular relations between antibody reactivity and regulatory
T-cells in unaffected relatives of SLE patients who often share SLE-associated
autoantibodies, our hypothesis is that these autoantibody-positive relatives
bear a particular capacity to regulate autoimmune reactions.
GROUP MEMBERS
Nuno Costa (Research Technician)
Sandra Iris Godinho (Masters student)
COLLABORATORS
Maria Berta Silva Martins (Instituto de Ciências Biomédicas Abel Salazar,
Porto, Portugal)
Carlos Vasconcelos (Hospital Geral de Santo Antonio, Porto, Portugal)
Margarida Lima (Hospital Geral de Santo Antonio, Porto, Portugal)
Cristina João (Centro de Investigação de Patologia Molecular, Lisboa,
Portugal)
Carlos Ferreira (Hospital de Santa Maria, Lisboa, Portugal)
Maria Francisca Fontes (Hospital Curry Cabral, Lisboa, Portugal)
José Alves (Hospital Fernando Fonseca, Amadora-Sintra, Portugal)
FUNDING
Fundação para a Ciência e Tecnologia (FCT), Portugal
LUPUS AND ITS COMPENSATION IN UNAFFECTED RELATIVES
BY T-CELL REGULATION
SLE is an autoimmune disease characterised by autoantibodies that accumulate
over years before clinical manifestation. Unaffected relatives of SLE patients
frequently share SLE-type autoantibodies, most without ever acquiring clinical
disease, which suggests a capacity to compensate pathogenic effects associated
with them. A therapy that is able to restore such compensation appears
highly desirable. Conversely to reported negative correlations of regulatory T-
cells with circulating IgG autoantibodies in patients, we found them positively
correlated in unaffected relatives. Furthermore, autoantibody profiles were influenced
by genetic polymorphisms affecting effects mediated by IL2, the cytokine
with the strongest impact on Treg function in characteristic ways. We
hypothesise that an IL2-dependent regulatory feedback mechanism, abrogated
in manifest SLE, can control the pathogenicity of SLE-type antibody production.
We are now characterising this mechanism. Data analysis is in progress
Scheme of SLE pathogenesis according to current knowledge, with the role of
regulatory T-cells indicated.
Cytogramme with subsets of conventional and regulatory T-cells.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
74

NEURONAL
STRUCTURE
AND FUNCTION
Inbal Israely Research Fellow
PhD in Neuroscience, University of California, Los Angeles, 2004
Post-doctoral Associate, MIT, USA
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Research Fellow at the IGC since 2009
link to external website
We are interested in understanding how activity can lead to specific structural
changes in neurons which may be important for learning, and how such changes
affect connectivity within neural circuits. It is unknown how the diverse forms
of activity that a neuron receives are physically stored and regulated at the
level of individual spines, the sites of neuronal connections. Does long lasting
depression lead to structural changes at synapses? What types of structural
and electrophysiological modifications take place at spines following complex
patterns of naturally occurring activity? Several mental retardation disorders in
humans are characterised by abnormal spine morphology, and studying neurons
from animal models may further our understanding of the relationship between
structure and function. We aim to combine molecular and genetic tools with
imaging and electrophysiological methodologies, to determine how information
is physically stored in the brain.
GROUP MEMBERS
Yazmin Ramiro Cortes (Post-doc)
Anna Hobbiss (PhD Student)
Ali Ozgur Argunsah (PhD Student)
COLLABORATORS
Thomas McHugh (Riken Brain Science Institute, Japan)
Devrim Ünay (Bahcesehir University, Turkey)
FUNDING
Champalimaud Foundation (CF), Portugal
Bial Foundation, Portugal
DENDRITIC COMPARTMENTALISATION OF PROTEIN SYNTHESIS-DEPENDENT
SYNAPTIC PLASTICITY
We found that protein synthesis dependent stimulation of spines can facilitate
plasticity at neighbouring spines for up to an hour and over long distances (70
micra). Through 2-photon imaging and uncaging of glutamate at individual spines,
we aim to visualise structural changes that occur in response to protein synthesis
dependent forms of activity. We will examine how activity at multiple spines leads
to structural changes and changes in synaptic weights within a dendritic branch.
We aim to determine whether competition for proteins during synaptic plasticity
can shape the organization of inputs within a dendrite, leading to the physical
clustering of synapses. We also investigate whether the clustering of synapses
can be observed following the development of neural circuits, by examining the
endogenous distribution of spines within dendrites of the hippocampus.
We find that the stimulation of multiple spines closely together in time can
lead to competition for cellular resources, and that new proteins are required
for this process. These findings demonstrate that synaptic plasticity may be
biologically constrained, and provides a potential mechanism through which
synapses could be spatially clustered. We are examining the parameters over
which competition is regulated, in order to define the learning rules for protein
synthesis dependent plasticity.
STRUCTURAL CORRELATES OF SYNAPTIC DEPRESSION AT DENDRITIC SPINES
Synaptic potentiation leads to an enlargement of spine head volumes at individual
synapses, however the structural correlates of synaptic depression are
poorly understood. Long term depression can be initiated through a variety of
receptors, and it is unknown whether the structural correlates of this form of
plasticity apply generally to any decrease of synaptic weight, or whether there
are specific modifications depending on which signalling pathway is activated.
We aim to determine what are the structural correlates of synaptic depression
at dendritic spines. In particular, we are interested in exploring long lasting
forms of synaptic depression that depend on new protein synthesis. We will
determine what are the parameters which govern these changes following activity
at specific inputs. Additionally, we will probe whether new proteins serve
to constrain plasticity at multiple spines similarly to the case for long term
potentiation.
We have induced long lasting synaptic depression through the activation of
metabotropic glutamate receptors (mGluRs) in hippocampal organotypic slice
cultures. We have quantified the structural changes which correlate with this
form of plasticity through 2-photon imaging of subsets of spines for up to four
hours. Additionally, we recorded electrophysiological responses from these
cells in order to monitor the changes following synaptic plasticity.
INDUCING ACTIVITY AT SINGLE DENDRITIC SPINES TO STUDY STRUCTURAL DYNAMICS.
Using 2-photon microscopy in living brain slices together with photoactivation
of caged glutamate, we can examine how neurons physically store information at
synapses. We can vary the type of stimulation delivered at a given input to mimic
different forms of activity, and study what are the structural and functional correlates.
We also examine how a neuron integrates information arriving at multiple
synapses.
IGC ANNUAL REPORT ‘11
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PLASTICITY CONSEQUENCES OF NATURALISTIC SPIKE TRAINS
AT SINGLE SYNAPSES
Naturally occurring patterns of activity are complex in structure and have an
irregular distribution of action potentials. Thus far, synaptic plasticity at individual
inputs has been assessed through delivery of regular patterns of activity.
We aim to mimic the varied input patterns observed in vivo with glutamate
uncaging at individual spines, in order to determine what are the structural
and plasticity correlates of these forms of activity. We will determine how such
complex trains of activity interact across multiple synapses within a dendritic
branch. We will use this information to model neuronal information processing
in order to develop an understanding of the learning rules which govern
synaptic weight changes.
We have established a collaboration in order to obtain in vivo electrophysiological
recordings from hippocampal CA3 neurons. Experiments in which electrophysiological
recordings are coupled with 2-photon imaging in hippocampal
organotypic slice cultures are underway in order to monitor the structural and
plasticity correlates of spike timing dependent plasticity. This form of plasticity
depends on the integration of events at single inputs, similarly to what is
observed endogenously.
AUTOMATIC DENDRITIC SPINE DETECTION AND ANALYSIS
The combination of live 2-photon imaging and glutamate uncaging allows us
to investigate how neuronal structure and function are correlated at the level
of individual spines following synaptic activity. In addition to changes in the
volume of the spine head, many other changes in spine structure have been
observed, for example, changes in the length of the spine neck. Such changes
are difficult to quantify with existing methodologies, and therefore we aim to
develop automated data analysis tools for handling both the large data sets
and the many variables to be analysed. We aim to achieve greater precision and
flexibility in the quantification of structural changes, as well as to significantly
enhance the efficacy of data analysis.
Thus far, we have developed an automated, multi-level, region based segmentation
method to detect dendritic spines from two-photon laser scanning microscopy
images. Identified structures in two-photon images of dendritic spines
are used to train the segmentation algorithm. This is the first step towards a
broader automated dendritic spine detection and analysis framework.
IGC ANNUAL REPORT ‘11
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NEUROETHOLOGY
LABORATORY
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Susana Lima Research Fellow
PhD in Neuroscience, Universidade de Lisboa, Portugal, 2005
Post-doctoral Fellow, Cold Spring Harbor Laboratory, USA
Research Fellow at the IGC since 2008
link to external website
The main goal of our laboratory is to gain mechanistic insights into the neuronal
processes underlying fundamental behaviours in females: the choice of a suitable
mate and how to initiate and terminate sexual behaviour. To do so, we use
mice as model system and a combination of approaches that include physiological,
anatomical and molecular tools to dissect the contribution of candidate
brain areas to the emergence of these natural behaviours. Our long-term goal
is to test the hypothesis that mate choice has an impact on the regulation of
sexual behaviour.
NEURONAL MECHANISMS FOR MATE CHOICE IN MICE
Our main goal was to develop a behavioural paradigm of mate choice in mice to then
investigate the neuronal mechanisms responsible for representing mates of different
values and how comparison of competing alternatives are made. We have used a
mate choice paradigm inspired by the natural situation observed in the hybrid zone
between Mus musculus musculus and Mus musculus domesticus in Europe.
GROUP MEMBERS
Léa Zinck (Post-doc)
Vanessa Urbano (Technician)
COLLABORATORS
Marta Moita (Champalimaud Neuroscience Programme, Portugal)
FUNDING
FP7 Marie Curie Reintegration Grant, European Commission
Bial Foundation, Portugal
Champalimaud Foundation, Portugal
PUBLIC ENGAGEMENT IN SCIENCE
Speed-dating at Optimus Alive (July)
Media Interviews (Falar Global, Jornal de Negócios, Diário de Notícias, RTP1)
We have established a mate choice paradigm with M. m. musculus and M. m.
domesticus, where musculus females exhibit a strong and reliable preference
for their own subspecies. We have also established that this preference is influenced
by early imprinting mechanisms and it increases with multiple testing.
Furthermore, the preference for a specific male is not absolute, but rather flexible
and dependent of the alternatives that are available.
NEURONAL MECHANISMS UNDERLYING SEX HORMONE-DEPENDENT SWITCH-
ING OF SEXUAL RECEPTIVITY
Female sexual receptivity changes across the reproductive cycle, being maximal
during the fertile phase. This represents an interesting state-dependent behavioural
output, where the interaction of sexual hormones and the physiology
of neuronal circuits alter the way a female treats the same male stimulus. We
are interested in understanding the role of the ventromedial nucleus of the
hypothalamus (VMH) in the control of this receptivity switch. To this end, we
are performing electrophysiological recordings of this area in naturally cycling
female mice exposed to male stimuli.
During the past year we have developed and troubleshooted electrophysiological
recordings in the VMH of naturally cycling, freely moving females. We are
able to record from well isolated neurons from this area, and we can observe
stimulus triggered responses. We are currently testing other types of electrodes
in order to increase the yield of these experiments.
Two subspecies of house mice in Europe, in allopatry: Mus musculus musculus
and Mus musculus domesticus. Musculus females prefer to mate with musculus
males, domesticus females mate indiscriminately. We have developed a behavioural
paradigm in the laboratory using inbred wild derived animals of the subspecies
musculus (PWD and PWK) and laboratory strains of mice (Black 6) as domesticus.
FEMALE SEXUAL BEHAVIOUR:
NEURONAL PATHWAYS FOR AROUSAL TERMINATION
Like all behaviours, sexual arousal has a beginning and an end. Sensory genital
stimulation received by the female during copulation (sensed by mechanoreceptors
present in the cervix and clitoris) is relayed to the brain and is important
for the rewarding effects of copulation and for its termination. Despite being
a fundamental aspect of sexual behaviour, very little is known about how the
brain integrates the genital stimulation received during copulation and how the
brain uses this information to inhibit further sexual arousal.
We have started by establishing a protocol to trace the genital input to the
brain, by using pseudo rabies viruses (PRV) expressing green fluorescent protein.
PRV infects axon terminals of neurons and after infecting a neuron, jumps
to synaptically connected neuronal partners. By employing this method we are
investigating which brain areas are synaptically connected to the genital organs
that receive stimulation during copulation.
PWD females exhibit a strong homosubspecific preference for PWK males, resembling
that observe in the wild.
An example of a putative hypothalamic neuron that responded selectively to female
presentations. Spike histogrammes are shown. This neuron shows selective
responses to the presentations of females from different strains (red).
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
77

ANTIGEN
PRESENTATION
AND T CELL ACTIVATION
Elisabetta Padovan Research Fellow
PhD in Immunology, University of Padova, Italy, 1994
Group Leader, Bern University Hospital, Switzerland
Principal Investigator at the IGC since 2006
T cells are central actors of antigen-specific immune responses and their function
is strongly influenced by the Antigen-presenting Cells (APC) they directly
interact with. APC control T cell activation also indirectly, by providing cytokines
that are induced by environmental triggers recognised by Pattern Recognition
Receptors (PRR). Although it has long been recognised that PRR on professional
APC instruct the cell fate decisions of naïve T lymphocytes, a careful analysis
of how PRR signalling modulates effector memory T cell function, directly and
indirectly through APC, is still missing. By studying the crosstalk between Monocyte/Macrophages
and T helper (Th) cells producing IL-17 (Th17) or IFN-γ (Th1)
we aim at dissecting how human Th17 and Th1 responses of healthy donors and
patients become tuned, also depending on the presence or absence of PRR
ligands.
HOW PATTERN RECOGNITION RECEPTORS (PRR) SIGNALLING CONTROLS
T LYMPHOCYTES ACTIVATION
Adaptive immunity depends on the induction of antigen-specific T cells in central
lymphoid organs, upon priming of naïve T cells by professional Antigen
Presenting Cells (APC) licensed through Toll-like Receptors (TLR). Up to now
it is still poorly known whether TLR signalling can also influence the crosstalk
between APC and CD4+ memory T cells, thus tuning T helper (Th) cell responses
in peripheral tissues. We use imaging techniques to resolve molecular events
occurring in living T cell/APC conjugates and dissect the modulatory effect of
TLR signalling on T cell immunity.
We have assessed the APC/T cell crosstalk established during antigen recognition.
The cytokine production pattern induced in Th17 cells activated by M1 and
M2 macrophages was assessed in 3D microscopy. Our imaging studies reveal
that IL-17 cytokine is contained in intracellular vesicles distributed around the
Microtubule Organising Centre (MTOC) of activated T cells, irrespective of the
type of APC (Figure 1 A). Quantitative analysis of our 3D images shows no differences
in the number of intracellular cytokine-containing vesicles and their
cytokine load.
COLLABORATORS
Perrine Paul-Gilloteaux (Institut Curie, Paris, France)
Claire Hivroz (Institut Curie, Paris, France)
A
B
CYTOKINE PRODUCTION PATTERN IN ACTIVATED TH17 CELLS.
A - 3D microscopy images show IL-17 (red) distributed around the T cell MTOC
(green) within a human Th17 clone recognising TSST-1 on M1 (left) and M2 (right)
Macrophages (blue). The quantitative analysis of up to 23 images plotted as total
number of IL-17 containing vesicles (top) and vesicles average fluorescence intensity
(bottom) is depicted in B.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
78

LEARNING
LABORATORY
THIS GROUP IS A MEMBER OF THE CHAMPALIMAUD NEUROSCIENCE PROGRAMME AT THE IGC
Joseph Paton Research Fellow
PhD in Neurobiology and Behaviour, Columbia University, 2008
Research Fellow at the IGC since 2008
link to external website
Learning to adaptively respond to cues in the environment that predict behaviourally
relevant events is critical for survival. However, in the natural world,
where animals are exposed to myriad sensory stimuli, learning the predictive
value of cues is non-trivial. How do animals figure out which cues are predictive,
and of what? This is called the credit assignment problem. Conceiving of
this problem as statistical inference in the time domain offers a parsimonious
account of animals’ learning abilities. In other words, when cues occur relative
to meaningful events is what determines their information content, their usefulness,
and thus, whether they warrant learning about. However, we still do not
understand how the brain might keep track of times. We aim to reveal neural
mechanisms for time by observing and manipulating neurophysiology in behaving
rodents performing tasks that lead them to estimate intervals.
GROUP MEMBERS
Gonçalo Lopes (PhD student, shared with Adam Kampff)
Gustavo Mello (PhD student)
Rui Azevedo (PhD student, shared with Zach Mainen))
Sofia Soares (Technician)
COLLABORATORS
Joshua T. Dudman (Janelia Farm Research Campus, USA)
Adam R. Kampff (Champalimaud Neuroscience Programme, Portugal)
FUNDING
Champalimaud Foundation (CF),Portugal
Fundação para a Ciência e a Tecnologia (FCT), Portugal
OPTOGENETIC INVESTIGATION OF INTERVAL TIMING IN MICE
In the past year, we have initiated a parallel set of timing studies in mice in
order to take advantage the increased molecular power of the mouse relative
to the rat. We have trained mice on a classic temporal reproduction task, called
the peak interval task, and are currently training mice on the SFI task mentioned
above. By combining viruses dependent on CRE recombinase activity
for expression of transgenes, with mouse lines expressing CRE in specific basal
ganglia cell types, we plan to express light sensitive channels and pumps in targeted
locations within the basal ganglia circuit. Stimulating these proteins with
light during experiments will provide us with two potentially powerful pieces of
data. First, we will be able to ask what type of cell we are recording from in vivo
much more easily and in higher volume than was available with older techniques.
Second, we can test hypotheses about the role of activity in specific populations
of neurons for timing behaviour.
In the past year Rui Azevedo has activated dopamine neurons using optogenetics
in brain slices, and in behaving mice. He gained behavioural evidence
of successful activation by showing that he could condition mice to prefer a
particular spatial location by illuminating transfected neurons specifically when
mice entered a particular region. He is currently training transgenic mice on a
timing task, and will test whether manipulation of dopamine neuron activity
affects interval timing.
NEUROPHYSIOLOGY OF TIME ENCODING IN THE RODENT STRIATUM
Lesion, pharmacology, and genetic studies all suggest that the ability to estimate
the passage of time on the scale of seconds to minutes is produced in
the striatum, a major input area of the basal ganglia. Thus, we trained rats to
estimate time intervals and recorded from striatal neurons as they behaved
and asked how the passage of time could be encoded in the firing patterns we
observed. In addition, the basal ganglia is thought to implement reinforcement
learning mechanisms, helping the animal learn how to act in response to a given
situation based on past experience. We sought to place the neural signals we
recorded into a computational framework that reconciles interval timing and
reinforcement learning. Towards that end, we are developing a computational
model of interval timing that includes signals related to those we observe experimentally,
but that also can solve reinforcement learning problems.
We currently have a manuscript in the final stages of preparation describing the
neural signals we observe during an interval timing task. We are also actively
extending these studies to gain more continuous measures of the animals’ behaviour
during our task. This will be important for continuing to rule out behavioural
sources of variance in the firing of neurons we record.
Modelling rats’ behaviour using mechanisms derived from experimental data. Output
of a timing model running on a task that we have previously trained rats to
perform. At the top are scalable temporal basis functions that resemble the activity
profiles of neurons we have recorded in the striatum of rats during this task.
These are used as rate functions to produce Poisson spike trains. These spike
trains are then decoded to estimate time (blue trace) and subsequently drive behaviour
(red threshold).
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
79

NEUROMETRIC - PSYCHOMETRIC COMPARISON OF INTERVAL TIMING
PERFORMANCE
Tasks in which subjects must categorise sensory stimuli whose characteristics
are parametrically varied have been powerful tools for relating neural processing
to sensation in a rigorous and quantitative manner. We are applying the
same approach to an unconventional sensory modality, the ability to sense the
passage of time, by training rats on a two alternative forced choice interval
timing task. We can derive quantitative description of animals’ interval timing
abilities via the fitting of psychometric functions to their choice data and then
compare this to the ability of neural activity to encode the passage of time.
A tight correspondence between the animals’ behavioural performance and the
neuronal encoding of time would suggest involvement of those neural signals
in the process of timing.
Thiago Gouvea has designed the behavioural apparatus, programmed the behavioural
control required for the task, and has trained four animals. We will
soon be initiating neural recordings during task performance.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
80

IMMUNE
REGULATION
Carlos E. Tadokoro Research Fellow
PhD in Immunology, University of São Paulo, 2001
Post-doctoral fellow, New York University, USA
Research Fellow at the IGC since 2010
link to external website
The ultimate function of the immune system is to cooperate with other body
systems in order to maintain homeostasis within multi-cellular organisms.
To perform such a task, cells and molecules of the immune system evolved to
distinguish between “self” and “non-self” molecules. We are interested in better
understanding the regulation that occurs inside the immune system, focusing
our attention on a particular cell type called regulatory T cell. We combine
classical cellular analyses with intra-vital imaging techniques to investigate the
function of immune cells in tissues under various conditions of activation/inflammation.
To this aim, we develop surgical procedures and tools to perform
these analyses using two-photon microscopy, which allow the observation of
single-cell dynamics and cell interactions as well as their spatial localization
inside the organs.
GROUP MEMBERS
Márcia M. Medeiros (Post-doc, started at November)
Henrique B. Da Silva (Visiting Ph.D. Student (collaborator))
Susana Caetano (Research Technician, started in September)
COLLABORATORS
Juan J. Lafaille (New York University, USA)
Michael L. Dustin (New York University, USA)
Cláudio R. F. Marinho (University of São Paulo, Brazil)
Maria Regina D'Império Lima (University of São Paulo, Brazil)
Ana Cláudia Zenclussen (Otto-von-Guerricke University, Germany)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
GENERATION OF NEW TRANSGENIC ANIMALS
FOR in vivo TRACKING OF REGULATORY T CELLS
The main objective of this project is to develop new tools to acquire information
about in vivo tracking of a specific type of cell inside the immune system
called Regulatory T Cells (Tregs). We will develop tools to allow the in vivo
cell fate mapping of Tregs inside organs and also throughout the rest of the
mouse body. We will develop new intra-vital microsurgeries, use “two-photon”
microscopy, and generate new genetically engineered animals to track any cell
of interest. The major challenge is no longer the microscopes used, but in the
development of intra-vital microsurgeries that allow the exposure of internal
organs with minimal or no trauma. Therefore, this project has a strong core in
Research and Development (R&D). To visualise these cells we will generate new
genetically manipulated mouse lines expressing a photo-activated GFP (paGFP)
under specific promoters and conditional transgenic mouse lines based on
“Tet ON-OFF” systems.
We developed intra-vital imaging techniques, in use by IGC groups (intra-vital
imaging of placenta, used by the Disease genetics group) or international collaborators;
submitted two papers: Zenclussen, A. C., et al, Clin. Invest; Silva, H.
B., et al, Eur. J. Immunol.); and published two papers: Olivieri, D., et al, J. Integr.
Bioinform., 2011 Sep 8(3):180).
A
B
In vivo PICTURE OF PLACENTA BLOOD FLOW.
A - Maternal blood in red and foetal blood in green, with arrow showing the region
of chorionic plate. B - Higher magnification of placenta, showing details of chorionic
plate and labyrinth zone.
3D reconstruction of uterus, showing DC distribution (green), during oestrus phase
of oestrus cycle.
IGC ANNUAL REPORT ‘11
RESEARCH FELLOWS
81

EXTERNAL ASSOCIATED RESEARCH GROUPS
THE FOLLOWING GROUPS DEVELOP THEIR RESEARCH AT EXTERNAL ASSOCIATED
INSTITUTES AND RESEARCH CENTRES, MAINTAINING STRONG SCIENTIFIC
COLLABORATIONS WITH IGC GROUPS AND ACCESS TO IGC FACILITIES
GASTRULATION
Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, Portugal
José António Belo Principal Investigator
NEOANGIOGENESIS
Instituto Português de Oncologia, Lisbon, Portugal and CEDOC-Centre for Chronic
Diseases, Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Portugal
Sérgio Dias Principal Investigator
EVOLUTIONARY ECOLOGY OF MICROORGANISMS
Faculdade de Ciências da Universidade de Lisboa, Portugal
Francisco Dionísio Principal Investigator
VASCULAR DEVELOPMENT
Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Portugal
António Duarte Principal Investigator
SYSTEMS IMMUNOLOGY
University of Vigo, Spain
José Faro Principal Investigator
YEAST STRESS
Escola Superior de Tecnologia da Saúde de Lisboa, Portugal
Lisete Fernandes Principal Investigator
CELLULAR IMMUNOLOGY
Instituto de Medicina Molecular, Portugal
Luis Graça Principal Investigator
DEVELOPMENTAL BIOLOGY
Instituto de Medicina Molecular, Portugal
Domingos Henrique Principal Investigator
TISSUE MORPHOGENESIS AND REPAIR
CEDOC - Chronic Diseases, Faculdade de Ciências Médicas, Universidade Nova
de Lisboa, Portugal
António Jacinto Principal Investigator
MALARIA
Instituto de Medicina Molecular, Portugal
Maria Mota Principal Investigator
AZORES GENETICS
Divino Espírito Santo Hospital, Azores, Portugal
Luísa Mota Vieira Principal Investigator
ANIMAL BEHAVIOUR
Instituto Superior de Psicologia Aplicada, Portugal
Rui Oliveira Principal Investigator
GENOMICS OF COMPLEX DISEASES
Instituto de Medicina Molecular, Portugal
Sofia Oliveira Principal Investigator
EMBRYONIC DEVELOPMENT OF VERTEBRATES
Instituto de Medicina Molecular, Portugal
Leonor Saúde Principal Investigator
MOLECULAR IMMUNOLOGY
Instituto de Medicina Molecular, Portugal
Bruno Silva Santos Principal Investigator
VIRAL PATHOGENESIS
Instituto de Medicina Molecular, Portugal
João Pedro Simas Principal Investigator
IGC ANNUAL REPORT ‘11
EXTERNAL GROUPS
82

STRESS AND CYTOSKELETON
Escola Superior de Tecnologia da Saúde de Lisboa, Portugal
Helena Soares Principal Investigator
DEVELOPMENT AND EVOLUTIONARY MORPHOGENESIS
Faculdade de Ciências da Universidade de Lisboa, Portugal
Solveig Thorsteinsdóttir Principal Investigator
HUMAN MOLECULAR GENETICS AND FUNCTIONAL ANALYSIS UNIT
Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, Portugal
Astrid Vicente Principal Investigator
IGC ANNUAL REPORT ‘11
EXTERNAL GROUPS
83

FACILITIES
AND SERVICES
IGC ANNUAL REPORT ‘11
FACILITIES AND SERVICES
84

ANIMAL
FACILITIES
Jocelyne Demengeot Head
PhD in Cellular and Molecular Biology, Université AIX-MARSEILLE II, 1989
PI of Lymphocyte Physiology Group
Head of Animal Facilities since 2002
The Animal House Facility is organised into several areas, specifically prepared
for each model organism hosted at the IGC.
RODENT FACILITY
The facility consists of five independent units: a production facility, two experimental
areas, a quarantine and a germ-free facility, which is part of the European
Mouse Mutant Archive (EMMA) consortium. In 2011, the Facility hosted over
150 mouse strains, 2 rat strains and was used by 23 research groups.
FISH FACILITY
The facility has a quarantine and a production/experimental area. It includes a
behaviour room and a microinjection room. In 2011 it hosted 22 zebrafish lines
and provided services to seven research groups.
FLY FACILITY
The facility hosts thousands of mutant lines. It is composed of several walk-in
chambers, a food preparation room, two procedure labs and a quarantine area.
In 2011, nine research groups used this facility.
FACILITY STAFF
Manuel Rebelo, PhD (Manager)
Ana Mena, PhD (Animal Research Project Officer)
Joana Bom (Technician)
Ana Sofia Leocádio (Technician)
Maysa Franco (Technician)
Ana Maria Ramos (Technician)
Carlos Pires (Caretaker in charge of Production Unit)
Samira Varela (Caretaker in charge of E0 Unit)
Graça Ramalho (Caretaker in charge of E1 Unit)
João Lopes (Caretaker in charge of Quarantine Unit)
Eusébia Varela (Caretaker)
Cláudia Gafaniz (Caretaker)
Autelinda Costa (Caretaker)
Olinda Queirós (Caretaker)
Luís Arroja (Caretaker)
Jelskey Gomes (Caretaker)
PUBLIC ENGAGEMENT IN SCIENCE
Talk for students, IGC and Oeiras (January, June, October)
Speed-dating at OptimusAlive! Music Festival, Oeiras (July)
FROG FACILITY
The facility has an aquatic habitat system and a bench for experimental work. In
2011, the facility was used by one research group.
MAJOR PROJECTS AND ACCOMPLISHMENTS
The EU-FP7 Infrafrontier consortium aims at building a world-class research
infrastructure for mutant mouse analysis and archiving that provides the biomedical
research community with the tools needed to unravel the role of gene
function in human disease. The grant supported the improvement of our legal
status, for all issues related to vertebrate experimental models. It also allowed
the Facility manager to visit several state-of-the-art facilities, for technical and
managerial exchanges.
EU-FP7 European Mouse Mutant Archive (EMMA) is a not-for-profit repository
for the collection, archiving (via cryopreservation) and distribution of mutant
mouse strains used in basic biomedical research. The laboratory mouse is the
main mammalian model for genetic and multi-factorial human diseases. EMMA
plays a crucial role in exploiting the tremendous potential benefits of current
research in mammalian genetics to human health. This grant maintains a stateof-the-art
germ-free facility, used by European and IGC researchers.
EQUIPMENT AND INFRASTRUCTURE
RODENT FACILITY:
• 7 autoclaves;
• 15 IVCs (Isolated Ventilated Cages) rack system;
• 6 Germ-Free Isolators;
• 1 osmosis reverse system;
• 1 vapor-phase hydrogen peroxide decontamination system;
• 1 transfer and decontamination chamber;
• 1 animal transfer chamber.
Funding Calouste Gulbenkian Foundation and EU-FP7 EMMA
IGC ANNUAL REPORT ‘11
FACILITIES AND SERVICES
85

FLY FACILITY:
• 18 work stations with CO2 output pedal system;
• 2 working stations with CO2 output flow buddy system;
• 1 microinjector;
• 1 boiling pan for food preparation, 80L capacity;
• 2 food dispensers;
• 2 heat shock baths.
Incubators:
• 1 room 25ºC
• 1 room 18ºC
• 1 behaviour room 25ºC
• 3 incubators 25ºC
Funding Calouste Gulbenkian Foundation, Portugal
FISH FACILITY:
• 1 ZebTEC system with 6 racks, total capacity of 300 tanks (3.5L);
• 1 Zebrafish system for Quarantine, capacity for 126 tanks (3.5L);
• 2 microinjectors;
• 2 microscopes;
• 2 incubators 28ºC.
Funding Calouste Gulbenkian Foundation, Portugal
The Animal Facilities include state-of-the-art services and equipment for mouse
(including a germ-free facility shown), fish and Drosophila, used by over 35 research
groups, including several external groups associated to the IGC.
IGC ANNUAL REPORT ‘11
FACILITIES AND SERVICES
86

TRANSGENICS
UNIT
Moisés Mallo Head
PhD in Molecular Biology, University of Santiago de Compostela, Spain, 1991
PI of the Patterning and Morphogenesis Group
Head of Facility since 2001
The Transgenics Unit is the gene manipulation unit. The unit provides transgenic
services to research staff. Both classic transgenics, by pronuclear microinjection,
and gene targeting, by blastocyst injection of embryonic ES cells, are
offered as a service. The unit also offers the cryopreservation of embryos for
long-term storage.
FACILITY STAFF
Ana Nóvoa (Research Technician)
MAJOR PROJECTS AND ACCOMPLISHMENTS
The work of the unit during 2011 mostly involved the genesis of transgenic mice
by pronuclear DNA injection. Most transgenics were produced by microinjection
into the FVB/N background. This year, we produced transgenic lines from
four different constructs. One of them was a BAC reporter. The other three
generated tools for conditional inactivation studies in mesodermal derivatives
and for labelling embryonic muscle precursors with fluorescent proteins to allow
their isolation from the living embryo using cell sorting approaches. The
rest of the transgenic production was not aimed at generating transgenic lines
because transgene expression resulted in embryonic lethal phenotypes. Therefore,
these injections were designed for studies using a transient transgenic
approach. During this year, we created transgenic embryos from more than 20
different constructs, including two different BACs. Similar to previous years, the
transgenic efficiency was kept high, being around 30% for normal transgenics
and 17% for transgenics injecting BAC constructs. The transgenic unit also produced
four chimeric mice from one strain of ES-cells by injection into C57BL/6
blastocysts. All these animals contained higher than 70% chimerism.
EQUIPMENT AND INFRASTRUCTURE
• 1 Microinjection setup with Nikon inverted microscope equipped with DIC
optics, and three dimensional Narishige micromanipulators;
• 1 Microinjection setup with Leica inverted microscope equipped with DIC
optics, and three dimensional, power assisted, Narishige micromanipulators;
• 2 FemtoJet pump;
• 1 Sutter P-87 Flaming/Brown micropipette puller;
• 1 Zeiss SV6 Stereomicroscope with training head;
• 2 Standard Zeiss SV6 Stereomicroscopes;
• 1 CO2 incubator;
• 1 Ultrasonic Cleaning Device.
Funding Calouste Gulbenkian Foundation and Fundação para a Ciência e a
Tecnologia, Portugal
TwoCellEmbryos - Mouse embryos at the two-cell stage.
IGC ANNUAL REPORT ‘11
FACILITIES AND SERVICES
87

PLANT
FACILITY
Paula Duque
Elena Baena-González
José Feijó
Jorg Becker
Users
The Plant Facility at the IGC ensures the growth and maintenance of Arabidopsis
thaliana plants, the model organism used by the plant research groups hosted
by the Institute. The facility consists of a custom-built greenhouse with lighting
control and temperature regulation and three custom-made fully controlled
growth chambers with short day, long day and continuous light settings, as well
as a walk-in plant growth room and three small reach-in chambers that allow the
performance of cell-based assays and more precise phenotypical analyses. Four
research groups (Plant Molecular Biology, Plant Stress Signalling, Cell Biophysics
and Development, and Plant Genomics) make use of the IGC Plant Facility as
they all use Arabidopsis as a model system in their experimental work.
FACILITY STAFF
Vera Nunes (Technician)
EQUIPMENT AND INFRASTRUCTURE
• 1 Walk-in Chamber (Aralab 10.000 EH 2009);
• 2 Reach-in Chambers (Aralab S600PLH);
• 1 Reach-in Chamber (Aralab D1200PL);
Funding Calouste Gulbenkian Foundation, Portugal
Reach-in chamber for cell-based assays and phenotypic analyses.
B
Walk-in plant growth room with Arabidopsis thaliana cultures.
One of the three custom-built fully-controlled growth chambers.
IGC ANNUAL REPORT ‘11
FACILITIES AND SERVICES
88

CELL IMAGING
UNIT
José Feijó Head
PhD in Cell Biology, Universidade de Lisboa, 1995
PI of Cell Biophysics and Development Group
Head of Facility since 2003
link to facility website
The main goal of the Cell Imaging Unit is to provide access to high-end technology
and cutting-edge technical support for bioscience research. We provide
a unique facility that allows ready access to a wide range of technologies and
expertise in an integrated manner that helps drive research forward efficiently.
The unit currently stands as an international reference laboratory for confocal
and multi-photon microscopy, as well as for high-throughput cell sorting.
The unit is well equipped, with two cell sorters, three confocal microscopes,
a DeltaVision deconvolution microscope system and two multi-photon microscopes,
besides a dozen more subsidiary and custom-made pieces of equipment.
Researchers are trained through regular workshops on basic and advanced light
microscopy techniques as well as in flow cytometry and image acquisition software.
Technical assistance is available when necessary to ensure collection of
high quality images and analysis of data. All users receive basic training in the
systems in use, in troubleshooting, and advice on experimental design. We have
developed a strong and broad base of users and continue to train new users.
Because microscopy is currently in high demand and new systems and techniques
are continuously being developed to meet increasing scientific needs, we try to
expand the facilities, to keep accessibility problems low, and introduce the latest
innovations (in microscopy and flow cytometry) to the research community.
FACILITY STAFF
Carlos Tadokoro (Multi-photon Microscopy Applications Manager /
Research Fellow)
Rui Gardner (Flow Cytometry Lab Manager)
Nuno Moreno (General Coordinator Microscopy)
Telma Lopes (Technician - Cell Sorting)
Francisco Henrique (Technician - Microscopy)
Pedro Almada (Technician - Microscopy)
MAJOR PROJECTS AND ACCOMPLISHMENTS
INTEGRATION OF A SCREENING MICROSCOPE
This microscope is fully automated and works with open source software, being
a good platform for on-the-fly analysis. The equipment uses fast filter wheels
and shutters which, together with a sensitive CCD camera, enable three colour
images in a 96 well plate in few minutes. For now, it has been used for automatic
stitching, producing images of full brain mice or fish slices.
UPGRADE OF MULTIPHOTON MICROSCOPY SYSTEM
The installation of a Prairie Ultima multiphoton microscope proceeded, with
individual user training being provided. A guidebook for correct use of this
microscope was developed, and technical support for microscope adjustment
to individual scientific projects (different types of samples) was carried out.
EQUIPMENT AND INFRASTRUCTURE
INSPECTION WIDE-FIELD LIGHT MICROSCOPES
• Olympus BH2;
• Olympus IMT-2;
• Leica DMLB2.
RESEARCH WIDEFIELD LIGHT MICROSCOPES
• Leica inverted DMIRE2;
• Leica upright DMRA2;
• Zeiss AxioImager M1.
Funding Calouste Gulbenkian Foundation and Fundação para a Ciência e a Tecnologia,
Portugal
CONFOCAL MICROSCOPES
• Leica SP5 (with resonant fast scanhead);
• Zeiss LSM 510 (with Meta detector);
• Andor Spinning disk (with EM-CCD intensified camera).
Funding Calouste Gulbenkian Foundation, Fundação para a Ciência e a Tecnologia
(FCT), Portugal, European Molecular Biology Organisation (EMBO).
TwoCellEmbryos - Mouse embryos at the two-cell stage.
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MULTIPHOTON
• Bio-Rad MRC 1024 with Coherent Mira-Verdi laser system;
• Prairie TPE microscope with Coherent Chameleon laser system (with double
scanhead, can take the two lasers for simultaneous excitation/imaging).
Funding Calouste Gubenkian Foundation
FLOW CYTOMETRY
• Cell Sorters;
• MoFlo;
• FACSAria.
Funding Calouste Gulbenkian Foundation and Fundação para a Ciência e a
Tecnologia, Portugal
ANALYSERS
• FACSCan;
• FACSCalibur;
• CyAn ADP (3 lasers, 9 fluo-detectors) Beckman Coulter.
Funding Calouste Gulbenkian Foundation and Fundação para a Ciência e a
Tecnologia, Portugal
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GENOMICS
UNIT
Carlos Penha Gonçalves Head
PhD in Immunology, University of Umea, 1999
PI of Disease Genetics Group
Head of Facility since 2003
The Unit provides technological support and expertise for research at the genome
scale and is composed by the Sequencing and Genotyping Services.
The Sequencing Service offers DNA sequencing and fragment analysis using
multicapillary with automatic sequencer ABI 3130XL. Taqman® Technology in
a 384-well format is also available to users both for SNP genotyping and Real-
Time PCR gene expression with 7900 HT Fast Real-Time PCR System.
FACILITY STAFF
Maria Isabel Marques (Senior Laboratory Manager)
João Costa (Genotyping Research Assistant)
Susana Ladeiro (Sequencing Research Assistant)
The Genotyping Service offers the Sequenom iPLEX technology, allowing rapid
SNP genotyping assays with up to forty SNPs assayed simultaneously. The facility
collaborates with researchers on: SNP choice and SNP Assay Design, Sequenom
Procedure and Data Management for Genetic Studies, providing access to
the BC/GENE interface software.
MAJOR PROJECTS AND ACCOMPLISHMENTS
GROUPS USING THE SEQUENCING SERVICE
• DNA Sequencing: Thirty in-house, five IGC associated groups and one non
IGC-associated groups used the ABI 3130XL Sequencing Service, with a total
of 11,880 samples sequenced between January and December 2011;
• Fragment Analysis/MIRUS: Four in-house groups used the ABI 3130XL Sequencing
Service with a total of 4,476 samples;
• Fast Real-Time PCR System: Twelve in-house, two IGC associated and three
non IGC-associated groups used 7900 HT on a regular basis (a total of
1,062 hours), to detect gene expression of several genes, on 20 different
projects.
GROUPS USING THE GENOTYPING SERVICE
Eleven internal, two IGC associated groups and seven non IGC-associated
groups used the Genotyping Service in 2011.
A total number of 1,282,560 SNP genotypes were produced between January
2010 and January 2011.
EQUIPMENT AND INFRASTRUCTURE
THE UNIT IS EQUIPPED WITH
• 2 robotic pipetting devices, robot PlateMate 2x2 (Matrix);
• 5 thermocycling machines - ABI 9700 equipped with 2x384 blocks;
• 1 Chip spotting robot (MassARRAY, Nanodispenser);
• 1 SNP detection, MALDI-TOF technology - MassARRAY Compact (Sequenom);
• 1 ABI 3130XL;
• 1 7900 HT Fast Real-Time PCR.
Funding Fundação para a Ciência e a Tecnologia, Portugal
External
26%
Internal
52%
IGC External
26%
Use of genotyping facility in 2011.
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GENE EXPRESSION
UNIT
Jörg Becker Head
PhD in Biology, University of Bielefeld, Germany, 2001
Research Fellow - Plant Genomics Group
Head of Facility since 2008
The Gene Expression Unit provides DNA microarray services, ranging from experimental
design over complete sample processing to expert advice on data
analysis. We have been an Affymetrix Core Lab with reference status for Gene-
Chip technology in Portugal since 2002. Running a total of 339 microarrays we
have contributed to 32 in-house, national and international projects in 2011
alone.
FACILITY STAFF
Júlia Lobato (Technician)
João Sobral (Technician, started in October)
SERVICES INCLUDE:
• Gene Expression Profiling (3’ IVT, Gene and Exon arrays);
• Genotyping, Cytogenetics (500K array set and SNP 6.0 array);
• Custom array projects;
• RNA and DNA quality analyses (Bioanalzyer);
• Data analysis training (dChip and Chipster).
MAJOR PROJECTS AND ACCOMPLISHMENTS
• Training SNP6 Cytogenetics (5 SNP6 Genotyping arrays for Gene Expression
Unit);
• Sperm Transcriptome (4 Drosophila arrays for Plant Genomics lab);
• NKTreg (5 Mouse arrays (Cellular Immunology lab for IGC associated group
at IMM);
• Myc Factor (1 Medicago arrays for Institute for Plant Genetics, Leibniz University
Hanover, Germany);
• AGP mutant pollen (6 Arabidopsis arrays for Department of Botany, Faculdade
de Ciências da Universidade do Porto, Portugal);
• Cholesterol and Metastasis (6 Human arrays for Centro de Investigação de
Patobiologia Molecular, Lisbon);
• Zinc Finger (3 Human arrays for Faculty of Pharmacy, University of Lisbon);
• Chein Myf5 (2 Mouse Tiling arrays for Patterning and Morphogenesis lab);
• Leukemia (16 human arrays for IGC associated group at IMM);
• Retinoic Acid in Enteric Lymphoid Organogenesis (8 Mouse arrays for IGC
associated group at IMM);
• Drg11 (20 Mouse arrays for Department of Experimental Biology, Faculdade
de Medicina da Universidade do Porto);
• Xspecies (4 Burkholderia arrays for Biological Sciences Research Group,
Instituto Superior Técnico, Lisbon);
• SNP6 Genotyping (3 SNP6 Genotyping arrays for Department of Genetics,
Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon);
• Small RNAs (15 Arabidopsis arrays for Oeiras Summer Schools in Evolutionary
Biology, IGC);
• Ontogeny vs. Phylogeny (15 Mouse arrays for Oeiras Summer Schools in
Evolutionary Biology, IGC);
• Regeneration in denervated fins (16 zebrafish arrays for IGC associated
group at IMM);
• Zymosan treatment (12 Anopheles/Plasmodium arrays for UEI Parasitologia
Médica, Instituto de Higiene e Medicina Tropical, Lisbon);
• Stem cell differentiation (2 Human arrays for Department of Medical Genetics,
Faculdade de Medicina da Universidade do Porto);
• Dis delta phenotype (6 Yeast arrays for Control of Gene Expression Lab, ITQB);
• BolA overexpression (6 E.coli arrays for Control of Gene Expression Lab, ITQB);
• NeoSuc clinical trial (34 human arrays for Computational Genomics Group, IGC);
• Cytogenetics (2 Cyto 2.7M arrays for Department of Genetics, Instituto Nacional
de Saúde Dr. Ricardo Jorge, Lisbon);
• Variants (12 Burkholderia arrays for Biological Sciences Research Group,
Instituto Superior Tecnico, Lisbon);
• LMD Myc (5 Medicago arrays for Institute for Plant Genetics, Leibniz University
Hanover, Germany);
B
Fluidics station for staining and washing up to 4 GeneChips in parallel.
Pseudo-coloured image of a GeneChip array after scanning, showing different signal
intensities depending on the expression level of the correspondent transcripts.
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• Low noise (6 Rat arrays for Instituto Superior Ciências da Saúde Egas Moniz,
Lisbon);
• Forest Biotech (12 Poplar arrays for Forst Biotech group, IBET);
• Malaria lipids (3 Mouse arrays for IGC associated group at IMM);
• SMc3169 (6 Medicago arrays for Biological Sciences Research Group, Instituto
Superior Tecnico, Lisbon);
• Breast Cancer (4 Human arrays for Centro de Investigação de Patobiologia
Molecular, Lisbon);
• FuncGrape (32 Vitis vinifera arrays for Genomics and Plant Breeding, Instituto
Superior de Agronomia, Lisbon);
• GWAS Behcet (16 SNP6 Genotyping arrays for IGC associated group at IMM);
• HIV (3 Human arrays for Infections and Immunity group, IGC).
EQUIPMENT AND INFRASTRUCTURE
• Scanner 3000 7G with Autoloader;
• Fluidics Station 450;
• Hybridization Oven 640;
• Bioanalyzer 2100.
Funding Fundação para a Ciência e a Tecnologia, Portugal
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HISTOPATHOLOGY
UNIT
Miguel P. Soares Head
PhD in Science, University of Louvain, Belgium, 1995
PI of Inflammation Group
Head of Facility since 2011
The Histopathology Unit provides a wide range of services related to tissue
preparation. These include collection, fixation, processing, embedding, sectioning
and staining of animal tissue samples. The unit also provides microscopy
assistance as well as training to new users in sample preparation and sectioning.
FACILITY STAFF
Ana Margarida Santos (Technician, left in October)
Joana Rodrigues (Technician)
EQUIPMENT AND INFRASTRUCTURE
• Tissue processor: takes the fixed tissues through a series of graded alcohol
baths, to dehydrate, then into xylene and finally paraffin will penetrate the
tissues;
• Paraffin embedding station and water bath: used to effect the paraffin
inclusion of cytological and histological samples;
• Microtome: sectioning instrument that allows for the cutting of extremely
thin slices of material. These sections are then observed under transmitted
light. Steel blades are used to prepare sections of animal or plant tissues
for light microscopy histology. Microtome sections have thickness between
0.05 and 10 µm;
• Cryostat: device used to maintain cold cryogenic temperatures of samples
and to cut histological slides from samples fixed and frozen in OCT;
• Vibratome: similar to a microtome but uses a vibrating razor blade to cut
through tissue. The vibration amplitude, the speed, and the angle of the
blade can all be controlled. Fixed or fresh tissue pieces are embedded in
low gelling temperature agarose. The resulting agarose block containing
the tissue piece is then glued to a metal block and sectioned while submerged
in a water or buffer bath. Individual sections are then collected
with a fine brush and transferred to slides or multiwell plates for staining.
Funding Calouste Gulbenkian Foundation, Portugal
B
HYALINE CARTILAGE.
Hyaline cartilage, mouse. Luxol fast blue (400x).
OVARIAN METASTASIS.
Ovarian mestastasis of breast cancer, mouse. Hematoxylin and eosin (200x).
IGC ANNUAL REPORT ‘11
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ION DYNAMICS
FACILITY
Ana Catarina Certal Head (until May 2011)
José Feijó Head (from June 2011)
PhD in Cell Biology, Universidade de Lisboa
Post-doc at IGC (C. Certal)
PI of Cell Biophysics and Development (J. Feijó)
Head of Facility since 2010
The Ion Dynamics Facility provides researchers with non-invasive technology for
measuring electric currents and specific ion fluxes in biological systems. We are
equipped with a Scanning Voltage Probe (SVET) and three Ion-Specific Probes
(SIET), all from Applicable Electronics. Both probes are set-up in inverted fluorescence
microscopes with high-resolution CCD cameras allowing the coupling
of real-time electrophysiological measurements with intracellular ion imaging.
In close collaboration with the Cell Imaging Unit, we also provide assistance and
advice for advanced ion imaging using both commercial dyes or genetically-encoded
ion probes. At present we have several projects being developed in plant
development (pollen tube growth), fly development (drosophila oogenesis) and
vertebrate organogenesis (zebrafish fin regeneration).
FACILITY STAFF
Teresa Gomes (Research Technician)
PUBLIC ENGAGEMENT IN SCIENCE
Talks for school students, IGC (April, October, December)
MAJOR PROJECTS AND ACCOMPLISHMENTS
ION DYNAMICS DURING DROSOPHILA OOGENESIS I
In Drosophila the establishment of both the anterior-posterior and dorsal-ventral
axes of the embryo depends on signalling provided by the Tgfa-like ligand
Gurken (Grk). When the oocyte nucleus lies close to the posterior pole of the
oocyte, an unknown signal leads to the repolarisation of the oocyte cytoskeleton.
As a consequence, the oocyte nucleus migrates to an anterior cortical
position where EGF signalling leads to the differentiation of the follicle cells
establishing DV polarity. Ion currents have been associated with processes that
contribute to the establishment of polarity in several biological systems. The
aim of this project is to determine if ion dynamics contribute to microtubule repolarisation
in Drosophila early development. Both the SIET technique to measure
ion fluxes and the SVET technique to measure total current are being used
in a histone-GFP line, on egg chambers during stages 4, 5 and 6 of oogenesis.
ION DYNAMICS DURING DROSOPHILA OOGENESIS II
With the results from the project developed by the group of Evolution and
Development we are measuring ion fluxes in 3 lines of histone-GFP Gurken mutant
egg chambers during stages 4, 5 and 6. Both techniques are used, SIET to
measure the ion fluxes and SVET to measure total current.
Ion dynamics as part of the regeneration mechanism of complex organs in vertebrates.
It has long been known that endogenous electric currents and electric
fields are important for vertebrate organ regeneration. Nevertheless, many
questions remain:
1. What is the ion nature of these currents?;
2. How is cellular ion dynamics during the regeneration process?;
3. Which are the molecular signalling pathways that transduce electric cues
into cellular responses?
We use zebrafish caudal fins as an adult regeneration model in vertebrates. Our
approach couples specific extracellular ion flux measurements, carried out using
a non-invasive Scanning Ion-Specific Electrode Technique (SIET), with transcriptional
profiling and genetic functional analysis.
Using SIET we detected dynamic fluxes for potassium (K+), calcium (Ca2+), chloride
(Cl-) and proton (H+) at different stages of the regeneration process. We
are now looking for candidate genes encoding transporters that mediate such
ion-specific fluxes. Microarray analysis revealed the proton pump V-ATPase as a
putative mediator of H+ fluxes. We are validating these data with both genetic
and pharmacological approaches, as well as advanced ion imaging. Overall, our
results suggest tightly-regulated ion-driven phenomena as part of the mechanism
of adult tissue regeneration.
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EQUIPMENT AND INFRASTRUCTURE
• Two Ion-Specific Probe (SIET) setups coupled with an inverted fluorescence
microscope (Nikon). SIET is equipped with a IPA-2 Ion/Polarographic
Amplifier and Computerised Motion Control (CMC-4), all from Applicable
Electronics, LLC. A Hamamatsu Camera controller and an illumination system
by Lambda DG-4 provide image acquisition. (Funding: Fundação para a
Ciência e a Tecnologia, Portugal; Fundação Calouste Gulbenkian, Portugal);
• ASIET setup coupled with a zoom scope imaging unit. The SIET comprises
an IPA-2 Ion/Polarographic Amplifier and Computerised Motion Control
(CMC-4), all from Applicable Electronics. (Funding: FP6 Network of Excellence
"Cells into Organs", European Commission);
• A Scanning Voltage Probe (SVET) coupled with an inverted microscope
(Nikon) equipped with a Phase Sensitive Detector Amplifier - 2 channel
(PSDA-2), a Computerized Motion Control (CMC-4), all from Applicable Electronics,
LLC. A Minicamera UK-1117-M CCD ensures image acquisition.
Funding Calouste Gulbenkian Foundation, Portugal
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BIOINFORMATICS
AND COMPUTATIONAL
BIOLOGY UNIT
José Pereira Leal Head
PhD in Biomedical Sciences, Universidade do Porto, Portugal, 2001
PI of Computational Genomics Group
Head of Facility since 2006
link to unit website
The unit´s mission is to promote the use of computational methods in biological
research, through training and development of resources and materials:
• Support the graduate programmes of the Oeiras Associated Laboratory (LAO);
• Provide technical and scientific direct user support in biological data analysis
using computational methods;
• Conduct research and development in bioinformatics, in particular in dataflow,
data warehousing and data analysis, supporting the LAO;
• Provide a computing infrastructure suited for biocomputing;
• Collaborate with middle and high schools producing bioinformatics activities
and introducing teachers and students to new methods of learning
biology.
FACILITY STAFF
Maria Isabel Marques (Senior Bioinformatics Specialist)
Paulo Almeida (Systems administrator & Programmer)
Renato Alves (Systems administrator & Programmer)
Isabel Neves (Researcher)
Patrícia Soares (Programmer)
PUBLIC ENGAGEMENT IN SCIENCE
Talks for school students (Loures)
Seminars for high-school teachers, Biology in Modern Times series, IGC, July
Teacher training in bioinformatics, January, February
MAJOR PROJECTS AND ACCOMPLISHMENTS
• inTB: Collaborative project with the Collective Dynamics group (IGC) and the
Genomics Facility (IGC) on an FCT grant designed to establish a molecular
framework for the study of epidemiology of tuberculosis in Portugal. We
have developed and implemented a new web-based database and on-line
analysis tool to support this project, the inTB: Integrating Clinical Demographic
and Molecular Data in Tuberculosis. Two papers are in production;
• CorkoakDB: A collaborative project with several groups at the Oeiras Associated
Laboratory, on an FCT grant for the sequencing of the ESTs of
the cork oak, in response to a call by Government. During this year, an
assembly and annotation pipeline was finished and a web application was
developed to present all the information to collaborators and eventually a
wider audience. Two papers are in production;
• FlowBase: Data warehousing environment for flow cytometry experiments.
We developed and implemented the whole system, which has been submitted
for publication. Other warehousing solutions are maintained in the unit
for microarray data;
• MTOC-explorer: We collaborate with the Computational Genomics Laboratory
(IGC) and Cell Cycle Regulation (IGC) in MTOC-explorer, a bioinformatics
resource that allows integrating morphological information from microscopy
images with genomic information. Images are annotated and curated by an
international team of domain experts in a broad range of eukaryotes using
a controlled vocabulary developed specifically for this task. By centralising
this knowledge, and using a controlled vocabulary, the resulting collection
of images can be mined in a way which is not possible when knowledge is
dispersed. At the moment, the database contains over 500 images from 100
species in all major eukaryotic branches. One paper is in production.
• Technical and scientific direct-user support: Eighteen IGC groups, seven
IGC-associated groups and five non IGC groups received extensive technical
and scientific support, including: Assembly (Staden); finding copy number
variation; SNP analysis; finding mutations; browsing genomes, finding genes,
transcripts, proteins, SNPs, microRNAs; transcript identification, alignments,
RT-PCR primers; morpholino design; browsing the mtocdb to search
for gene orthologues/paralogues; transcription binding factors: Transfac,
Genomatix, Galaxy; searching for homologues-BLASTS: finding homologues,
orthologues and paralogues; finding and analysing protein families;
clustering proteins according to protein families: domain searching;
patterns searching; finding isoforms; Interpro and SuperFamily searching;
identifying and counting microRNAs in sequencing libraries; phylogenetic
analysis: Phylip, MrByes and Pymol; PhenomicDB database; Script design:
perl script for Blasting and parsing FASTA files; support in NGS analysis
data; script for DNA sequencing to automate the analysis; bioinformatics
software consulting. We contributed to the production of Master and PhD
Theses, papers, and scientific communications.
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• Bioinformatics in high schools: We have developed an inquiry-based learning
tool based on bioinformatics for high schools now extended to other
levels, and a teacher training-program. We are maintaining this system,
adding functionality, and recruiting new schools and teachers to this experiment
of using bioinformatics in the classroom. Fourteen schools of
11 cities, in four Portuguese districts are following the project: S. Miguel
Torga, Queluz; E. S. Quinta do Marquês, Oeiras; EB3 Secundária Vila Cova
da Lixa; E. S. José Afonso, Loures; E. S. Engº A. C. Duarte, Marinha Grande;
E. S. Stuart Carvalhais, Queluz; E. S. de Mem Martins, Mem Martins, E. S.
Luís de Camões, Lisboa, E. S. Gama Barros, Cacém, E. S. Miguel Cargaleiro,
Fogueteiro, E. S. De Azambuja, Azambuja and E. B. D. Sancho I, Pontével,
Cartaxo. One paper is in production.
EQUIPMENT AND INFRASTRUCTURE
• Two heavy calculation servers used for support and hosted projects;
• Three servers dedicated to hosting research databases and web resources;
• Seven workstations of which two have analysis software for user access;
• Four redundant backup servers.
Funding Fundação para a Ciência e a Tecnologia, Portugal
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PORTUGUESE
BIOINFORMATICS
CENTRE
Pedro Fernandes (Eng) Head
PhD in Biomedical Sciences, Universidade do Porto, Portugal, 2001
Head of Facility since 2005
link to facility website
Head of IGC Gulbenkian Training Programme
in Bioinformatics (GTPB)
The CPB-RAP was created in 2005. It hosts Hermes, a mid size cluster that is
dedicated to Bioinformatics. Access to this cluster is free but users need an
account. This is a high performance platform, therefore more suitable for heavy
computations than for trivial jobs. To make good use of this machine, applications
usually require deep modifications to allow for the use of the parallel
processing capabilities. Most of the machine load is taken by lengthy simulation
jobs for Population Genetics and by occasional orthologue searches using multiple
BLAST jobs with pen domain software like InParanoid.
PUBLIC ENGAGEMENT IN SCIENCE
Talks for students, IGC, May, June
MAJOR PROJECTS AND ACCOMPLISHMENTS
• Assigning multi-site genotypes to their subpopulations;
• PAS, a new data-mining method that flags statistically significant intercolumnar
non-randomness of any complexity;
• MultiLocus Sequence Typing using eBURST goeBURST and new methods;
• MTBSS - Mycobacterium Tuberculosis Bioinformatic and Structural Strategies
Towards Treatment - New Indigo - ERANET - Official start Sept 2010.
EQUIPMENT AND INFRASTRUCTURE
• IBM JS20 Blade computer (60), and associated control, management and
storage.
Funding Fundação para a Ciência e a Tecnologia, Portugal
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RESEARCH
FUNDING AFFAIRS
Sheila Vidal Head
PhD in Physiology of Invertebrates, Paris Sud XI University, Orsay, France, 2004
Head of Service since 2008
The Research Funding Affairs team is responsible for the implementation of a
pre-award grant administration service. Its main goal is to increase the IGC’s
capacity to attract research funds and to improve direct fundraising by research
teams, and their scientific projects, for competitive calls launched by national,
international, public and private grant programmes.
FACILITY STAFF
Mariana Guerreiro (Assistant, left in August)
This team reports directly to the IGC Director, understands the different grant
financial policies and requirements and works in collaboration with researchers,
project managers and finance staff.
SERVICES INCLUDE:
1. Identifying, in a timely manner, calls for proposals that might interest the
IGC, evaluating the conditions and preferences for grant applications (eligibility,
deadlines, how to apply and prepare full proposals, filling-in forms
and web-pages, knowing how it works, what are the specific targets, what
is behind each call, etc) and disseminating these opportunities through by
several means: the Grant Information website, emails, meetings;
2. Supporting proposal development and submission, namely: arranging administrative
forms, host documents and signatures, assisting with scientific
proposal writing and budget;
3. Post-award negotiation with funding agencies of contracts and agreements;
4. Grant application training for research staff and graduate students.
In addition, this team also monitors the impact of the services offered through
the quantification of the following criteria: number of applications submitted,
secured grants and prizes, diversity of grant agencies and amounts raised.
In 2011 this team supported researchers in attracting 34 new external competitive
research grants (18: FCT; 3: EC-FP7; 14: other sources, FLAD, Fundação
Bial, Camara Municipal de Oeiras, Associação Viver a Ciência, PORLISBOA/QREN,
SPD/Novo Nordisk, Association for International Cancer & Wellcome Trust)
raising a total of 4.9million Euro.
The Research Funding Affairs’ responsibilities cease with contract signature and
after passing all grant information to the accounting department and researchers.
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INNOVATION
AND TECHNOLOGY
TRANSFER
David Cristina Head
PhD in Genetics of Ageing, Universidade Nova de Lisboa, 2008
Head of Service since 2009
Technology Transfer (TT) is the exploitation, commercial or otherwise, of scientific
research for the direct benefit of society. Its activities include sourcing
invention disclosures, guaranteeing patent protection, licensing technologies,
forming spin-out companies and managing consultancy opportunities for scientists.
Technology Transfer is an undisputed source of social and economic
growth internationally and an absolute necessity for institutions set on seeing
their research have a direct, global impact on society, such as the IGC. Our
Technology Transfer Office works as a liaison between industry and academia,
facilitating communication between these two, very different, sectors. We offer
several services to researchers, including: counselling on industry relations,
assistance with intellectual property issues and sourcing of sponsored research
agreements.
INFORMATICS
João Sousa Head
PhD in Theoretical Biochemistry, Universidade de Lisboa, 2004
Head of facility since 2005
The Informatics Unit at the IGC (ITI) manages most of the IT needs of the institute.
We manage the IGC servers and network and provide various levels of support
for the heterogeneous workstations and servers dedicated to research.
We rely almost exclusively on Open Source for the services we provide. These
services include E-Mail, VPN, printing, hosting of servers and services for
researchers, administrative and collaborative Intranet services, central data
storage, database and web site maintenance, surveillance and access control,
consulting, training and, evidently support.
FACILITY STAFF
João Garcia (Systems Analyst)
Fernando Azevedo (Technician)
Manuel Carvalho (Technician)
Ana Maya (Technician)
Mário Neto (Systems Administrator)
The IGC network infrastructure is almost exclusively gigabit, for servers and
desktops, and we have full Wi-Fi coverage indoors and in selected areas outdoors.
The IGC Internet connection is provided by FCCN Academic Network
RCTS Services with a bandwidth of 50 Mbit/sec.
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LIBRARY
Margarida Meira Head
Head of facility since 2000
The Instituto Gulbenkian de Ciência library is an open access, specialised library in
biomedicine. Its bibliographic collection covers Biology, Biochemistry, Genetics, Pharmacology,
Microbiology, Physiology, Immunology, Virology, Cell Biology, Neuroscience
and Developmental Biology. The library is intended for researchers, faculty and visiting
scientists, students and staff of the IGC, but is also open to external users, either
from the national scientific community or from higher education institutions. It aims
to provide access to useful, diversified and up to date information, to improve services
provided, to acquire, register, maintain and distribute scientific information of
interest to or produced by researchers and students who work at the IGC.
The IGC library has a collection of printed journals in the field of health sciences,
that spans almost 30 years. Currently it subscribes approximately 325 international
scientific journals in electronic version. In addition, since 2004, the library belongs
to the national consortium Biblioteca do Conhecimento Online (b-on), which provides
online access to the contents of about 22,000 international scientific journals
and 18,000 e-books from 19 publishers, as well as to an important scientific
bibliographic database - the Web of Knowledge, which provides access to titles,
abstracts and citation and impact factor reposts of approximately 8,500 journals,
with records since 1945.
EQUIPMENT
AND MAINTENANCE
Nuno Moreno Head
PhD in Biophysics, Universidade Nova de Lisboa, 2010
Head of Service since 2008
Equipment and Maintenance is a technical platform responsible for ensuring
effective equipment acquisition, distribution and usage. This year, it was fused
with the building maintenance and therefore accumulating related responsibilities.
We work closely with scientific facilities in order to provide cutting edge
service and a smooth workflow, ensuring high equipment up-time.
Our services include: equipment repair and maintenance, building of small
hardware apparatus, several in house, open source systems, namely, an online
resource scheduler, a small scientific database management system, a remote
resource monitoring system. We run a seminar series "Tech Minutiae" with the
aim of raising awareness, amongst scientists, of the most cutting edge techniques.
FACILITY STAFF
Ana Homem (Research Technician)
João Lagarto (Engineer)
Tiago Vale (Engineer)
Revez da Silva (Technician - ARSPLUS)
Pedro Lourenço (Technician - GDFSUEZ)
PUBLIC ENGAGEMENT IN SCIENCE
Talks for school students, Alverca (April)
Guided tour of Miguel Palma's exhibition at CAM, Fundação Calouste
Gulbenkian, Lisbon (April)
We also work with the Direction of the institute in helping new labs set up in
terms of equipment and space management.
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ADMINISTRATION
AND ACCOUNTS
José Mário Leite (Eng) Head
Head of Service since 1999
IGC Deputy Director
This service provides support in all administrative matters, including ordering
and stores, travel arrangements, auditoria and venue preparations, visitors, and
new IGC researchers and students reception.
The accounts office provides invaluable support in preparing financial reports
of research projects, and in general management of accounts.
FACILITY STAFF
Teresa Meira (Direction Secretary, left in December)
Fátima Mateus (Accounts Officer)
João Nunes (Accounts Officer, Left in July)
Tatiana Rocha (Accounts Officer)
Ana Maria Santos (Accounts Officer)
Ana Lícia Pires (Accounts Officer, left in August)
Jorge Costa (Administrative Assistant)
Abílio Simões (Stores Manager)
Teresa Sousa (Receptionist)
Carlos Nunes (Driver, left in December)
António Sousa (Maintenance)
António Bretanha (Procurement)
ETHICS
COMMITTEE
Maria Francisca Fontes Head
PhD in Immunology, Universidade de Lisboa, 2009
MD, Hospital Curry Cabral, Lisbon
Head of Ethics Committee since 2011
The mission of the IGC Ethics Committee is to review all research projects involving
humans and animals to ensure that full consideration has been given
to animal welfare and the ethical implications of the research. It is the Ethics
Committee's responsibility to analyse all ethical issues that may arise during the
course of the research projects developed by the groups or units of the IGC,
including those specifically related to projects which entail studies with humans
or animal research.
ETHICS COMMITTEE MEMBERS
Carlos Penha-Gonçalves (Principal Investigator, IGC)
Rui Costa (Principal Investigator, IGC)
Manuel Rebelo (Animal Facilities Manager, IGC)
Ana Mena (Post-doc, IGC)
Luís Pinheiro (MD, External Member)
Ana Runkel (External member, Oeiras City Council)
José Athayde Tavares (Lawyer, External member)
Greta Martins (Lay member, IGC)
The Ethics Committee is an interdisciplinary body made up of nine members,
three of whom are laypersons and four are external to the IGC. In 2011, the Ethics
Committee approved 9 research projects.
IGC ANNUAL REPORT ‘11
FACILITIES AND SERVICES
103

RESEARCH
STRUCTURES

NATIONAL AND INTERNATIONAL
RESEARCH STRUCTURES
LABORATÓRIO ASSOCIADO ITQB (LA-ITQB)
Coordinator: Luís Paulo N. Rebelo (ITQB Director)
Since January 2011, following a re-structure, the LA-ITQB brings together the
Instituto de Tecnologia Química e Biológia (ITQB-UNL), the Instituto Gulbenkian
de Ciência (IGC), the Instituto de Biologia Experimental e Tecnológica (IBET) and
the Centro de Estudos de Doenças Crónicas (CEDOC-UNL). The current LA-ITQB
is a successor of a previous, smaller consortium, set up in 2001, between ITQB,
IBET, and a few groups of IGC, as one of the first Associated Laboratories in
Portugal. In its present form, it is a much wider partnership whose main aim is
to carry out a collaborative research programme, underpinned by a strong communications
network and sharing of infrastructures, namely libraries, scientific
facilities, academic services, and administrative support.
It is currently one of the broadest Associated Laboratories in terms of scientific
expertise, spanning research areas from Chemistry to Medicine, along the following
research themes:
1. Synthesis, structure, and function of biologically important molecules;
2. From genetics, cell and developmental biology to pathogenesis and novel
therapies;
3. Computational and theoretical biology: from biochemistry to medicine;
4. Host-microbe and host-cancer interactions;
5. Plant genomics and stress responses;
6. Evolution of ecosystems, biological risk, and food safety.
In 2011, research at the LA-ITQB involved 350 PhD holders (post-docs, group
leaders), produced 425 Web of Science-referenced papers, over 10,000 WoS
citations, 45 Highly Cited Papers (world top 1%), an average of one PhD thesis
awarded per week. Across the four research institutes, there were over 380
running projects, with several funding sources including over €5M from the European
Commission. Also in 2011, a further €3.5M euros income in I&D contracts
with the private sector was secured.
CHAMPALIMAUD FOUNDATION NEUROSCIENCE PROGRAMME AT THE IGC
Head: Zachary Mainen
PhD in Neurosciences, University of California, San Diego, 1995
Principal Investigator - Systems Neuroscience Group
The Champalimaud Neuroscience Programme (CNP) was created in 2007
through a collaborative agreement between the Champalimaud Foundation and
the Calouste Gulbenkian Foundation. It is a basic research team with the broad
aim of understanding brain function through integrative biological approaches.
CNP laboratories apply advanced molecular, physiological and imaging techniques
to elucidate the function of neural circuits and systems in animal models
that include Drosophila, mouse, rat and zebrafish.
As of December 2011 the CNP comprises sixteen independent research groups,
including thirteen in-house principle investigators, one research fellow and two
associated external principle investigators. This year, the CNP was joined by
three new investigators (C. Machens, L. Petreanu, A. Renart), one research fellow
(A. Kampff), and recruited another investigator who will join the programme in 2012.
In 2011, CNP investigators published 3 review articles and 10 refereed research
articles, including a study on the role of the dendritic branch in the potentiation
pattern of single synapses, which was published in Neuron (I. Israely). Also, at
the end of 2011, CNP investigators R. Costa and M. Carey received the International
Early Career Scientist Award by Howard Hughes Medical Institute.
The CNP also organises the International Neuroscience Doctoral Programme
(INDP). In this programme students are provided with a broad educational background
through both formal classes and hands-on experience in basic topics
in contemporary neuroscience such as cellular and synaptic physiology, sensation
and action and cognitive neuroscience. Quantitative approaches are
emphasised and students also receive background courses in mathematics and
programming.
IGC ANNUAL REPORT ‘11
RESEARCH STRUCTURES
105

In 2011, CNP investigators began conducting their research at the recently inaugurated
Champalimaud Center for the Unknown (CCU). There, in September
2011, the first Champalimaud Neuroscience Symposium was held, featuring lectures
by key neuroscientists from across the world. Soon after, the Ar monthly
event-series began. These outreach events, targeted at a general audience,
explore different aspects of scientific and science-related topics such as
human-machine interface and creativity.
In-house Principal Investigators:
• Megan Carey (Neural Circuits and Behaviour)
• Rui Costa (Neurobiology of Action)
• Inbal Israely (Neuronal Structure and Function)
• Susana Lima (Neuroethology)
• Christian Machens (Theoretical Neuroscience)
• Zach Mainen (Systems Neuroscience)
• Marta Moita (Behavioural Neuroscience)
• Michael Orger (Vision to Action)
• Joe Paton (Learning Laboratory)
• Leopoldo Petreanu (Cortical Circuits)
• Alfonso Renart (Circuit Dynamics & Computation)
• Carlos Ribeiro (Behaviour and Metabolism)
• Luísa Vasconcelos (Innate behaviour)
Research Fellows:
• Adam Kampff (Intelligent Systems)
External Principal Investigators:
• Domingos Henrique (Developmental Biology)
• Rui Oliveira (Animal Behaviour)
FLAD COMPUTATIONAL BIOLOGY COLLABORATORIUM
Head: Luís Rocha
PhD in Systems Science, State University of New York, 1997
Principal Investigator - Complex Adaptive Systems and Computational Biology
The main aim of the FLAD Computational Biology Collaboratorium is to establish,
enable, and foster an international, collaborative network of associated
institutions and scientists. It is an open host organisation designed to enable
intense cooperation amongst researchers from national and international institutions:
the centre hub of a collaborative network of research institutions. Its
principal objectives are to provide suitable facilities for visiting scientists, and
to host informatics technology to enable continuing off-site collaboration and
research in mathematical and computational biology.
The Collaboratorium operates in close synergy with the PhD Programme in
Computational Biology: faculty is encouraged to stay longer periods of time to
participate in work groups and collaborative projects hosted by the Collaboratorium.
Likewise, visitors to the Collaboratorium are encouraged to give seminars
and interact with students and faculty of the PhD Programme. Furthermore,
the PhD programme will help identify research areas in mathematical and computational
biology that are not yet sufficiently developed in Portugal. Reciprocally,
the growing collaboration network fostered by the Collaboratorium, will facilitate
the insertion of the newly formed computational biology PhDs within the
Portuguese research and technology communities.
IGC ANNUAL REPORT ‘11
RESEARCH STRUCTURES
106

PUBLICATIONS
IGC ANNUAL REPORT ‘11
RESEARCH STRUCTURES
107

PEER-REVIEWED PAPERS
1.
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15.
Abi-Haidar A, Rocha LM. (2011). Collective Classification of Textual Documents
Using Self-Organized Cross-Regulation in the Adaptive Immune System.
Evolutionary Intelligence 4(2):69-80.
Agua-Doce A, Graca L. (2011). Prevention of House Dust Mite Induced Allergic
Airways Disease in Mice through Immune Tolerance. PLOS ONE 6 (7):
Article Number: e22320.
Alcobia I, Gomes A, Saavedra P, Laranjeiro R, Oliveira S, Parreira L, Cidadao
A. (2011). Portrayal of the Notch System in Embryonic Stem Cell-Derived
Embryoid Bodies. Cells Tissues Organs 193(4):239-252.
Ascenso OS, Marques JC, Santos AR, Xavier KB, Rita Ventura M, Maycock CD.
(2011). An efficient synthesis of the precursor of AI-2 the signalling molecule
for inter-species quorum sensing. Bioorganic Medicinal Chemistry
19(3):1236-41.
Athanasiadis A. (2011). Zalpha-domains: At the intersection between RNA
editing and innate immunity. Seminars in Cell & Developmental Biology
23(3):275-280 [Epub ahead of print - 6 November 2011] .
Atsak P, Orre M, Bakker P, Cerliani L, Roozendaal B, Gazzola V, Moita M,
Keysers C. (2011). Experience Modulates Vicarious Freezing in Rats: A Model
for Empathy. PLOS ONE 6(7): Article Number: e21855.
Azevedo AS, Grotek B, Jacinto A, Weidinger G, Saude L. (2011). The Regenerative
Capacity of the Zebrafish Caudal Fin Is Not Affected by Repeated
Amputations. PLOS ONE 6(7): Article Number: e22820.
Azevedo D, Antunes M, Prag S, Ma X, Hacker U, Brodland GW, Hutson MS,
Solon J, Jacinto A. (2011). DRhoGEF2 Regulates Cellular Tension and Cell
Pulsations in the Amnioserosa during Drosophila Dorsal Closure. PLOS ONE
6 (9): Article Number: e23964.
Azoitei M, Correia B, Ban Y-EA, Carrico C, Kalyuzhniy O, Chen L, Schroeter
A, Huang P-S, McLellan J, Kwong PD, Baker D, Strong RK, Schief WR. (2011).
Computation-Guided Backbone Grafting of a Discontinuous Motif onto a
Protein Scaffold. Science 334(6054):373-376.
Barreto VM, Magor BG. (2011). Activation-induced cytidine deaminase
structure and functions: A species comparative view. Developmental and
Comparative Immunology 35(9):991-1007.
Beldade P, Mateus AR, Keller RA. (2011). Evolution and molecular mechanisms
of adaptive developmental plasticity. Molecular Ecology 20 (7):1347-63
Bento M, Correia E, Tavares AT, Becker JD, Belo JA. (2011). Identification
of differentially expressed genes in the heart precursor cells of the chick
embryo. Gene Expression Patterns 11(7):437-447.
Bergmann JH, Rodriguez MG, Martins NMC, Kimura H, Kelly DA, Masumoto
H, Larionov V, Jansen LET, Earnshaw WC. (2011). Epigenetic engineering
shows H3K4me2 is required for HJURP targeting and CENP-A assembly on
a synthetic human kinetochore. EMBO Journal 30(2):328-340.
Bettencourt-Dias M, Hildebrandt F, Pellman D, Woods G, Godinho SA. (2011).
Centrosomes and cilia in human disease. Trends in Genetics 27(8): 307-15.
Bilici T, Mutlu S, Kalaycioglu H, Kurt A, Sennaroglu A, Gulsoy M. (2011).
Development of a thulium (Tm:YAP) laser system for brain tissue ablation.
Lasers in Medical Science 26 (5):699-706.
16. Boavida LC, Borges FS, Becker JD, Feijo JA. (2011). Whole-genome analysis of
gene expression reveals coordinated activation of signaling and metabolic
pathways during pollen-pistil interactions in Arabidopsis thaliana. Plant
Physiology 155(4):2066-2080.
IGC ANNUAL REPORT ‘11
PUBLICATIONS
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17.
18.
19.
20.
21.
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23.
24.
25.
26.
27.
28.
29.
30.
Bolasco G, Tracey-White DC, Tolmachova T, Thorley AJ, Tetley TD, Seabra
MC, Hume AN. (2011). Loss of Rab27 function results in abnormal lung epithelium
structure in mice. American Journal of Physiology-Cell Physiology
300(3):C466-C476.
Borges F, Pereira PA, Slotkin RK, Martienssen RA, Becker JD. (2011). Micro-
RNA activity in the Arabidopsis male germline. Journal of Experimental
Botany 62(5):1611-1620 Sp Iss.
Borralho PM, Simoes AES, Gomes SE, Lima RT, Carvalho T, Ferreira DMS,
Vasconcelos MH, Castro RE, Rodrigues CMP. (2011). miR-143 Overexpression
Impairs Growth of Human Colon Carcinoma Xenografts in Mice with Induction
of Apoptosis and Inhibition of Proliferation. PLOS ONE 6(8) Article
Number: e23787.
Bouvignies G, Vallurupalli P, Hansen DF, Correia BE, Lange O, Bah A, Vernon
RM, Dahlquist FW, Baker D, Kay L. (2011). Solution structure of a minor and
transiently formed state of a T4 lysozyme mutant. Nature 477(7362):111-134.
Bouzid D, Fourati H, Amouri A, Marques I, Abida O, Haddouk S, Ben AM,
Tahri N, Penha-Goncalves C, Masmoudi H. (2011). The CREM gene is involved
in genetic predisposition to inflammatory bowel disease in the Tunisian
population. Human Immunology 72(12):1204-1209.
Brás-Pereira C, Zhang T, Pignoni F, Janody F. (2011). Homeostasis of the
Drosophila adult retina by actin-capping protein and the Hippo pathway.
Communicative & Integrative Biology 4(5):612-5.
Bshary R, Oliveira RF, Grutter AS. (2011). Short-Term Variation in the
Level of Cooperation in the Cleaner Wrasse Labroides dimidiatus: Implications
for the Role of Potential Stressors. Ethology 117(3):246-253.
Budd ME, Antoshechkin IA, Reis C, Wold BJ, Campbell JL. (2011). Inviability of
a DNA2 deletion mutant is due to the DNA damage checkpoint. Cell Cycle
10(10):1690-1698.
Caiado F, Carvalho T, Silva F, Castro C, Clode N, Dye JF, Dias S. (2011). The
role of fibrin E on the modulation of endothelial progenitors adhesion differentiation
and angiogenic growth factor production and the promotion
of wound healing. Biomaterials 32(29):7096-105.
Caramalho I, Rodrigues-Duarte L, Perez A, Zelenay S, Penha-Gonçalves C,
Demengeot J. (2011). Regulatory T cells Contribute to Diabetes Protection
in Lypopolissacharide-Treated Non-Obese Diabetic Mice. Scandinavian
Journal of Immunology 74(6):585-95.
Carvalho TP, Buonomano DV. (2011). A novel learning rule for long-term
plasticity of short-term synaptic plasticity enhances temporal processing.
Frontiers in integrative neuroscience 5:20.
Carvalho-Santos Z, Azimzadeh J, Pereira-Leal JB, Bettencourt-Dias M. (2011).
Evolution: Tracing the origins of centrioles cilia and flagella. The Journal of
Cell Biology 194(2):165-75.
Casalou C, Costa A, Carvalho T, Gomes AL, Zhu ZP, Wu Y, Dias S. (2011).
Cholesterol Regulates VEGFR-1 (FLT-1) Expression and Signaling in Acute
Leukemia Cells. Molecular Cancer Research 9(2):215-224.
Castro DS, Guillemot F. (2011). Old and new functions of proneural factors revealed
by the genome-wide characterization of their transcriptional targets.
Cell Cycle 10(23):4026-4031.
31. Chaouiya C, Naldi A, Remy E, Thieffry D. (2011). Petri net representation of
multi-valued logical regulatory graphs. Natural Computing 10(2):727-750
Sp Iss SI.
IGC ANNUAL REPORT ‘11
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32.
33.
34.
35.
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39.
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44.
45.
46.
Chiang L, Ngo J, Schechter JE, Karvar S, Tolmachova T, Seabra MC, Hume
AN, Hamm-Alvarez SF. (2011). Rab27b regulates exocytosis of secretory
vesicles in acinar epithelial cells from the lacrimal gland. American Journal
of Physiology-Cell Physiology 301(2):C507-C521.
Coelho FC, Codeço CT, Gomes MG. (2011). A bayesian framework for parameter
estimation in dynamical models. PLOS One 6(5):e19616.
Conceição IC, Long AD, Gruber JD, Beldade P. (2011). Genomic Sequence
around Butterfly Wing Development Genes: Annotation and Comparative
Analysis. PLOS One 6(8):e23778.
Correia BE, Holmes MA, Huang PS, Strong RK, Schief WR. (2011). High-resolution
structure prediction of a circular permutation loop. Protein Science
20(11):1929-34.
Correia DV, Fogli M, Hudspeth K, da Silva MG, Mavilio D, Silva-Santos B. (2011).
Differentiation of human peripheral blood V delta 1(+) T cells expressing
the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia
cells. Blood 118(4):992-1001.
Costa RM. (2011). A selectionist account of de novo action learning. Current
opinion in neurobiology 21(4):579-86.
Costa SS, Andrade R, Carneiro LA, Goncalves EJ, Kotrschal K, Oliveira RF. (2011).
Sex Differences in the Dorsolateral Telencephalon Correlate with Home
Range Size in Blenniid Fish. Brain Behavior and Evolution 77(1):55-64.
Costa N, Pires AE, Gabriel AM, Goulart LF, Pereira C, Leal B, Queiros AC,
Chaara W, Moraes-Fontes MF, Vasconcelos C, Ferreira C, Martins J, Bastos
M, Santos MJ, Pereira MA, Martins B, Lima M, João C, Six A, Demengeot
J, Fesel C. (2011). Active regulatory T-cells contribute to broadened T-cell
repertoire diversity in ivIg-treated SLE patients. Journal of Translational
Medicine 9 Suppl 2:P6.
Cruz AV, Mallet N, Magill PJ, Brown P, Averbeck BB. (2011). Effects of dopamine
depletion on information flow between the subthalamic nucleus and
external globus pallidus. Journal of Neurophysiology 106(4):2012-2023.
Debarros A, Chaves-Ferreira M, d'Orey F, Ribot JC, Silva-Santos B. (2011).
CD70-CD27 interactions provide survival and proliferative signals that
regulate T cell receptor-driven activation of human γδ peripheral blood
lymphocytes. European Journal of Immunology 41(1):195.
De Oliveira VL, Almeida SC, Soares HR, Crespo A, Marshall-Clarke S, Parkhouse
RM. (2011). A novel TLR3 inhibitor encoded by African swine fever
virus (ASFV). Archives of Virology 156(4):597-609.
Didier G, Remy E, Chaouiya C. (2011). Mapping multivalued onto Boolean
dynamics. Journal of Theoretical Biology 270(1):177-184.
Diekmann Y, Seixas E, Gouw M, Tavares-Cadete F, Seabra MC, Pereira-Leal
JB. (2011). Thousands of rab GTPases for the cell biologist. PLOS Computational
Biology 7(10):e1002217.
Duque P. (2011). A role for SR proteins in plant stress responses. Plant
Signaling and Behavior 1;6(1):49-54.
Faustino L, Mucida D, Keller AC, Demengeot J, Bortoluci K, Sardinha LR,
Takenaka MC, Basso AS, Faria AMC, Russo M. (2012). Regulatory T Cells
Accumulate in the Lung Allergic Inflammation and Efficiently Suppress
T-Cell Proliferation but Not Th2 Cytokine Production. Clin Dev Immunol
2012:721817 (Published online 2011 November 15).
47. Fernandes AS, Pedro Goncalves A, Castro A, Lopes TA, Gardner R, Glass
NL, Videira A. (2011). Modulation of fungal sensitivity to staurosporine by
targeting proteins identified by transcriptional profiling. Fungal Genetics
and Biology 48(12):1130-1138.
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48.
49.
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61.
Fernández BG, Gaspar P, Brás-Pereira C, Jezowska B, Rebelo SR, Janody F.
(2011). Actin-Capping Protein and the Hippo pathway regulate F-actin and
tissue growth in Drosophila. Development 138(11):2337-46.
Ferreira A, Marguti I, Bechmann I, Jeney V, Chora A, Palha NR, Rebelo S,
Henri A, Beuzard Y, Soares MP. (2011). Sickle Hemoglobin Confers Tolerance
to Plasmodium Infection. Cell 145 (3):398-409.
Figueiredo LF, de Gossmann T, Ziegler M, Schuster S. (2011). Pathway analysis
of NAD(+) metabolism. Biochemical Journal 439:341-348 .
French CA, Jin X, Campbell TG, Gerfen E, Groszer M, Fisher SE, Costa RM. (2011).
An aetiological Foxp2 mutation causes aberrant striatal activity and alters
plasticity during skill learning. Molecular Psychiatry [Epub ahead of print].
Galhardo L, Vital J, Oliveira RF. (2011). The role of predictability in the stress
response of a cichlid fish. Physiology & Behavior 102(3-4):367-372
Galhardo L, Almeida O, Oliveira RF. (2011). Measuring motivation in a cichlid
fish: An adaptation of the push-door paradigm. Applied Animal Behaviour
Science 130(1-2):60-70.
Gil FN, Gonçalves AC, Jacinto MJ, Becker JD, Viegas CA. (2011). Transcriptional
profiling in Saccharomyces cerevisiae relevant for predicting alachlor
mechanisms of toxicity. Environmental Toxicology and Chemistry
30(11):2506–2518.
Gonçalves L, Filipe M, Marques S, Salgueiro AM, Becker JD, Belo JA. (2011).
Identification and functional analysis of novel genes expressed in the Anterior
Visceral Endoderm. The International journal of developmental biology
55(3):281-95.
Gonçalves LG, Borges N, Serra F, Fernandes PL, Dopazo H, Santos H. (2011).
Evolution of the biosynthesis of di-myo-inositol phosphate a marker of adaptation
to hot marine environments. Environmental Microbiology [Epub
ahead of print].
Gonzalez LM, Ramiro R, Garcia L, Parkhouse RME, McManus DP, Garate T.
(2011). Genetic variability of the 18 kDa/HP6 protective antigen in Taenia
saginata and Taenia asiatica: Implications for vaccine development.
Molecular and Biochemical Parasitology 176(2):131-134.
Gonçalves-Sá J, Murray A. (2011). Asymmetry in sexual pheromones is not
required for ascomycete mating. Current Biology 21(16):1337-46.
Gouveia LO, Sobral J, Vicente AM, Ferro JM, Oliveira SA. (2011). Replication of
the CELSR1 association with ischemic stroke in a Portuguese case-control
cohort. Atherosclerosis 217(1):260-262.
Govindarajan A, Israely I, Huang SY, Tonegawa S. (2011). The dendritic branch
is the preferred integrative unit for protein synthesis-dependent LTP.
Neuron 69:132-146.
Gozzelino R, Soares MP. (2011). Heme Sensitization to TNF-Mediated Programmed
Cell Death. Advance Experimental Med Biol 691:211-219.
62. Grbić M, Van Leeuwen T, Clark RM, Rombauts S, Rouzé P, Grbić V, Osborne
EJ, Dermauw W, Ngoc PC, Ortego F, Hernández-Crespo P, Diaz I, Martinez M,
Navajas M, Sucena É, Magalhães S, Nagy L, Pace RM, Djuranović S, Smagghe
G, Iga M, Christiaens O, Veenstra JA, Ewer J, Villalobos RM, Hutter JL, Hudson
SD, Velez M, Yi SV, Zeng J, Pires-da-Silva A, Roch F, Cazaux M, Navarro
M, Zhurov V, Acevedo G, Bjelica A, Fawcett JA, Bonnet E, Martens C, Baele
G, Wissler L, Sanchez-Rodriguez A, Tirry L, Blais C, Demeestere K, Henz SR,
Gregory TR, Mathieu J, Verdon L, Farinelli L, Schmutz J, Lindquist E, Feyereisen
R, Van de Peer Y. (2011). The genome of Tetranychus urticae reveals
herbivorous pest adaptations. Nature 479(7374):487-92.
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63.
64.
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67.
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76.
Guerrero A, Carneiro J, Pimentel A, Wood CD, Corkidi G, Darszon A. (2011).
Strategies for locating the female gamete: the importance of measuring
sperm trajectories in three spatial dimensions. Molecular Human Reproduction
17(8) Special Issue: SI 511-523.
Guimarãis M, Gregório A, Cruz A, Guyon N, Moita MA. (2011). Time determines
the neural circuit underlying associative fear learning. Frontiers in
behavioral neuroscience 5:89.
Henriques ES, Brito RMM, Soares H, Ventura S, de Oliveira VL, Parkhouse
RME. (2011). Modeling of the Toll-like receptor 3 and a putative Toll-like
receptor 3 antagonist encoded by the African swine fever virus. Protein
Science 20(2):247-255.
Hogekamp C, Damaris A, Pereira P, Becker JD, Hohnjec N, Küster H. (2011).
Laser-microdissection unravels cell-type specific transcription in arbuscular
mycorrhizal roots including CAAT-box TF gene expression correlating
with fungal contact and spread. Plant Physiology 157(4):2023-43.
Hume AN, Seabra MC. (2011). Melanosomes on the move: a model to understand
organelle dynamics. Biochemical Society Transactions 39(5):1191-1196.
Hume AN, Wilson MS, Ushakov DS, Ferenczi MA, Seabra MC. (2011). Semiautomated
analysis of organelle movement and membrane content: understanding
Rab-motor complex transport function. Traffic 12(12):1686-701.
Janody F, Treisman J. (2011). Requirements for Mediator Complex Subunits
Distinguish Three Classes of Notch Target Genes at the Drosophila Wing
Margin. Developmental Dynamics 240(9):2051-2059.
Jesus AA, Liphaus BL, Silva CA, Bando SY, Andrade LEC, Coutinho A,
Carneiro-Sampaio M. (2011). Complement and antibody primary immunodeficiency
in juvenile systemic lupus erythematosus patients. LUPUS
20(12):1275-1284.
Jezowska B, Fernández BG, Amândio AR, Duarte P, Mendes C, Brás-Pereira C,
Janody F. (2011). A dual function of Drosophila capping protein on DE-cadherin
maintains epithelial integrity and prevents JNK-mediated apoptosis.
Developmental Biology 360(1):143-59.
Kawasumi A, Nakamura T, Iwai N, Yashiro K, Saijoh Y, Belo JA, Shiratori H,
Hamada H. (2011). Left-right asymmetry in the level of active Nodal protein
produced in the node is translated into left-right asymmetry in the lateral
plate of mouse embryos. Developmental Biology 353(2):321-330.
Kirilenko P, He G, Mankoo B, Mallo M, Jones R, Bobola N. (2011). Transient
activation of Meox1 is an early component of the gene regulatory network
downstream of Hoxa2. Molecular and Cellular Biology 31(6):1301-1308.
Konrad KR, Wudick MM, Feijó JA. (2011). Calcium regulation of tip growth:
new genes for old mechanisms. Current Opinion in Plant Biology 14(6):721-30.
Lima FA, Moreira-Filho CA, Ramos PL, Brentani H, Lima L de A, Arrais M,
Bento-de-Souza LC, Bento-de-Souza L, Duarte MI, Coutinho A, Carneiro-
Sampaio M. (2011). Decreased AIRE Expression and Global Thymic Hypofunction
in Down Syndrome. Journal of Immunology 187(6):3422-3430.
Lin J-Y, Lin W-J, Hong W-H, Hung W-C, Nowotarski SH, Gouveia SM, Cristo I,
Lin K-H. (2011). Morphology and organization of tissue cells in 3D microenvironment
of monodisperse foam scaffolds. Soft Matter 7(21):10010-10016.
77. Lourenço A, Conover M, Nematzadeh A, Pan F, Wong A, Shatkay H, Rocha
LM. (2011). A Linear Classifier Based on Entity Recognition Tools and a Statistical
Approach to Method Extraction in the Protein-Protein Interaction
Literature. BMC Bioinformatics 12(Suppl 8):S12.
IGC ANNUAL REPORT ‘11
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112

78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
90.
91.
Krallinger M, et al. (2011). The Protein-Protein Interaction tasks of BioCreative
III: classification/ranking of articles and linking bio-ontology concepts
to full text. BMC Bioinformatics 12(Suppl 8):S3.
Mahtani-Patching J, Neves JF, Pang DJ, Stoenchev KV, Aguirre-Blanco AM,
Silva-Santos B, Pennington DJ. (2011). PreTCR and TCR gamma delta Signal
Initiation in Thymocyte Progenitors Does Not Require Domains Implicated
in Receptor Oligomerization. Science Signaling 4(182) Article Number: ra47.
Manso H, Krug T, Sobral J, Albergaria I, Gaspar G, Ferro JM, Oliveira SA,
Vicente AM. (2011). Variants in the inflammatory IL6 and MPO genes modulate
stroke susceptibility through main effects and gene-gene interactions.
Journal of Cerebral Blood Flow & Metabolism 31(8):1751-1759.
Marcelino E, Martins T, Morais JB, Nolasco S, Cortes H, Hemphill A, Leitao
A, Novo C. (2011). Besnoitia besnoiti protein disulfide isomerase (BbPDI):
Molecular characterization expression and in silico modeling. Experimental
Parasitology 129(2):164-174.
Marengo EB, de Moraes LV, Melo RL, Balan A, Fernandes BL, Tambourgi DV,
Rizzo LV, Sant'Anna OA. (2011). A Mycobacterium leprae Hsp65 Mutant as a
Candidate for Mitigating Lupus Aggravation in Mice. PLOS ONE 6(9): Article
Number: e24093.
Marques JC, Lamosa P, Russell C, Ventura R, Maycock C, Semmelhack MF,
Miller ST, Xavier KB. (2011). Processing the Interspecies Quorum-sensing
Signal Autoinducer-2 (AI-2) Characterization of Phospho-(S)-45-Dihydroxy-
23-Pentanedione Isomerization by LsrG PROTEIN. Journal of Biological
Chemistry 286(20):18331-18343.
Martins BMC, Swain PS. (2011). Trade-Offs and Constraints in Allosteric
Sensing. PLOS Computational Biology 7(11):Article Number: e1002261.
Martins H, Villesen P. (2011). Improved Integration Time Estimation of Endogenous
Retroviruses with Phylogenetic Data. PLOS ONE 6(3):Art. Nº e14745.
Martins M, Rosa A, Guedes LC, Fonseca BV, Gotovac K, Violante S, Mestre T,
Coelho M, Rosa MM, Martin ER, Vance JM, Outeiro TF, Wang L, Borovecki F,
Ferreira JJ, Oliveira SA. (2011). Convergence of miRNA Expression Profiling
alpha-Synuclein Interaction and GWAS in Parkinson's Disease. PLOS ONE
6(10): Article Number: e25443
Mateus AM, Gorfinkiel N, Schamberg S, Arias AM. (2011). Endocytic and
Recycling Endosomes Modulate Cell Shape Changes and Tissue Behaviour
during Morphogenesis in Drosophila. PLOS ONE 6(4): Art. Nº e18729.
Mateus AM, Arias AM. (2011). Patterned Cell Adhesion Associated with Tissue
Deformations during Dorsal Closure in Drosophila. PLOS ONE 6(11): Article
Number: e27159.
Mateus O, Araujo R, Natario C, Castanhinha R. (2011). A new specimen of
the theropod dinosaur Baryonyx from the early Cretaceous of Portugal and
taxonomic validity of Suchosaurus. Zootaxa (2827):54-68.
McCue AD, Cresti M, Feijo JA, Slotkin RK. (2011). Cytoplasmic connection
of sperm cells to the pollen vegetative cell nucleus: potential roles of the
male germ unit revisited. Journal of Experimental Botany 62(5):1621-1631
Sp Iss SI.
McLellan JS, Correia BE, Chen M, Yang YP, Graham BS, Schief WR, Kwong
PD. (2011). Design and Characterization of Epitope-Scaffold Immunogens
That Present the Motavizumab Epitope from Respiratory Syncytial Virus.
Journal of Molecular Biology 409(5):853-866.
92. Mendonca AG, Alves RJ, Pereira-Leal JB. (2011). Loss of Genetic Redundancy
in Reductive Genome Evolution. PLOS Computational Biology 7(2): Art. Nº
e1001082
IGC ANNUAL REPORT ‘11
PUBLICATIONS
113

93.
94.
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
105.
106.
107.
Michard E, Lima PT, Borges F, Silva AC, Portes MT, Carvalho JE, Gilliham M,
Liu L-H, Obermeyer G, Feijó JA. (2011). Glutamate Receptor-like Genes Form
Ca 2+ Channels in Pollen tubes and are regulated by Pistil D-Serine. Science
332(6028):434-7.
Moura RA, Cascão R, Perpétuo I, Canhão H, Vieira-Sousa E, Mourão AF,
Rodrigues AM, Polido-Pereira J, Queiroz MV, Rosário HS, Souto-Carneiro
MM, Graca L, Fonseca JE. (2011). Cytokine pattern in very early rheumatoid
arthritis favours B-cell activation and survival. Rheumatology (Oxford)
50(2):278-82.
Mourao-Sa D, Robinson MJ, Zelenay S, Sancho D, Chakravarty P, Larsen
R, Plantinga M, Van Rooijen N, Soares MP, Lambrecht B, Reis e Sousa C.
(2011). CLEC-2 signaling via Syk in myeloid cells can regulate inflammatory
responses. European Journal of Immunology 41(10):3040-3053.
Naldi A, Remy E, Thieffry D, Chaouiya C. (2011). Dynamically consistent
reduction of logical regulatory graphs. Theoretical Computer Science
412(21):2207-2218.
Nascimento R, Costa H, Dias JD, Parkhouse RM. (2010). MHV-68 Open Reading
Frame 20 is a nonessential gene delaying lung viral clearance. Archives
of Virology Nov. 23 156(3):375-386.
Nascimento R, Costa H, Parkhouse RM. (2011). Virus manipulation of cell cycle.
Protoplasma [Epub ahead of print].
Oliveira M, Braga S, Passos-Coelho JL, Fonseca R, Oliveira J. (2011). Complete
response in HER2+leptomeningeal carcinomatosis from breast cancer
with intrathecal trastuzumab. Breast Cancer Research and Treatment
127(3):841-844.
Oliveira RF, Canario AVM. (2011). Nemo through the looking-glass: a commentary
on Desjardins & Fernald. Biology Letters 7(4):487-488.
Oliveira RF, Silva JF, Simoes JM. (2011). Fighting Zebrafish: Characterization
of Aggressive Behavior and Winner-Loser Effects. Zebrafish 8(2):73-81.
Oliveira VG, Caridade M, Paiva RS, Demengeot J, Graca L. (2011). Sub-optimal
CD4(+) T-cell activation triggers autonomous TGF-β-dependent conversion
to Foxp3(+) regulatory T cells. European Journal of Immunology
41(5):1249-55.
Olivieri D, Faro J, Gomez-Conde I, Tadokoro CE. (2011). Tracking T and B
cells from two-photon microscopy imaging using constrained SMC clusters.
J Integr Bioinform 8(3):180.
Peca J, Feliciano C, Ting JT, Wang WT, Wells MF, Venkatraman TN, Talaignair
N, Lascola CD, Fu ZY, Feng GP. (2011). Shank3 mutant mice display autisticlike
behaviours and striataldysfunction. Nature 472(7344):437-442.
Pereira AL, Martins M, Oliveira MM, Carrapico F. (2011). Morphological and genetic
diversity of the family Azollaceae inferred from vegetative characters
and RAPD markers. Plant Systematics and Evolution 297(3-4):213-226.
Perfeito L, Sousa A, Gordo I. (2011). Fitness effects of mutations in bacteria.
Journal of Molecular Microbiology and Biotechnology 21(1-2).
Portugal S, Carret C, Recker M, Armitage AE, Goncalves LA, Epiphanio S,
Sullivan D, Roy C, Newbold CI, Drakesmith H, Mota MM. (2011). Host-mediated
regulation of superinfection in malaria. Nature Medicine 17(6):732-U126.
108. Proenca CC, Gao KP, Shmelkov SV, Rafii S, Lee FS. (2011). Slitrks as emerging
candidate genes involved in neuropsychiatric disorders. Trends in Neuroscience
34(3):143-53.
IGC ANNUAL REPORT ‘11
PUBLICATIONS
114

109.
110.
111.
112.
113.
114.
115.
116.
117.
118.
119.
120.
121.
122.
123.
Ramiro RS, Alpedrinha J, Carter L, Gardner A, Reece SE. (2011). Sex and
Death: The Effects of Innate Immune Factors on the Sexual Reproduction
of Malaria Parasites. PLOS Pathogens 7(3): Art. Nº e1001309.
Ray-Gallet D, Woolfe A, Vassias I, Pellentz C, Lacoste N, Puri A, Schultz DC,
Pchelintsev NLA, Adams PD, Jansen LET, Almouzni G. (2011). Dynamics of
Histone H3 Deposition In Vivo Reveal a Nucleosome Gap-Filling Mechanism
for H33 to Maintain Chromatin Integrity. Molecular Cell 44(6):928-941.
Real C, Remedio L, Caiado F, Igreja C, Borges C, Trindade A, Pinto-do-O P,
Yagita H, Duarte A, Dias S. (2011). Bone Marrow-Derived Endothelial Progenitors
Expressing Delta-Like 4 (Dll4) Regulate Tumor Angiogenesis. PLOS
ONE 6(4): Art. Nº e18323.
Rezola A, de Figueiredo LF, Brock M, Pey J, Podhorski A, Wittmann C,
Schuster S, Bockmayr A, Planes FJ. (2011). Exploring metabolic pathways
in genome-scale networks via generating flux modes. Bioinformatics
15;27(4):534-540.
Ribeiro T, Santos S, Marques MIM, Gilmore M, Lopes MDS. (2011). Identification
of a new gene vanV in vanB operons of Enterococcus faecalis.
International Journal of Antimicrobial Agents 37(6):554-557.
Ribot JC, deBarros A, Silva-Santos B. (2011). Searching for signal 2: costimulation
requirements of gamma delta T cells. Cellular and Molecular Life
Sciences 68(14):2345-2355.
Rickenbacher E, Greve DN, Azma S, Pfeuffer J, Marinkovic K. (2011). Effects
of alcohol intoxication and gender on cerebral perfusion: an arterial spin
labeling study. Alcohol 45(8):725-37.
Ros AFH, Lusa J, Meyer M, Soares M, Oliveira RF, Brossard M, Bshary R.
(2011). Does access to the bluestreak cleaner wrasse Labroides dimidiatus
affect indicators of stress and health in resident reef fishes in the Red Sea?
Hormones and Behavior 59(1):151-158.
Saenko SV, Marialva MS, Beldade P. (2011). Involvement of the conserved
Hox gene Antennapedia in the development and evolution of a novel trait.
Evodevo 19;2:9.
Santos FJ, Costa RM, Tecuapetla F. (2011). Stimulation on demand: closing
the loop on deep brain stimulation. Neuron 72(2):197-8.
Santos ME, Athanasiadis A, Leitao AB, DuPasquier L, Sucena E. (2011). Alternative
Splicing and Gene Duplication in the Evolution of the FoxP Gene
Subfamily. Molecular Biology and Evolution 28(1):237-247.
Serpa J, Dias S, (2011). Metabolic cues from the microenvironment act as a
major selective factor for cancer progression and metastases formation.
Cell Cycle 10(2):180-181.
Serrano M, Real G, Santos J, Carneiro J, Moran CP Jr, Henriques AO. (2011).
A Negative Feedback Loop That Limits the Ectopic Activation of a Cell
Type-Specific Sporulation Sigma Factor of Bacillus subtilis. PLOS GENETICS
7(9): Article Number: e1002220.
Sharma R, Stuckas H, Bhaskar R, Khan I, Goyal SP, Tiedemann R. (2011). Genetically
distinct population of Bengal tiger (Panthera tigris tigris) in Terai
Arc Landscape (TAL) of India. Mammalian Biology 76(4):484-490.
Silva A, Laranjeira ABA, Martins LR, Cardoso BA, Demengeot J, Yunes JA,
Seddon B, Barata JT. (2011). IL-7 Contributes to the Progression of Human
T-cell Acute Lymphoblastic Leukemias. Cancer Research 71(14):4780-4789.
124. Silva AC, Filipe M, Steinbeisser H, Belo JA. (2011). Characterization of Cer-
1 cis-regulatory region during early Xenopus development. Development
Genes and Evolution 221(1):29-41.
IGC ANNUAL REPORT ‘11
PUBLICATIONS
115

125.
126.
127.
128.
129.
130.
131.
132.
133.
134.
135.
136.
137.
138.
139.
Silva IN, Ferreira AS, Becker JD, Zlosnik JEA, Speert DP, He J, Mil-Homens
D, Moreira LM. (2011). Mucoid morphotype variation of Burkholderia multivorans
during chronic cystic fibrosis lung infection is correlated with changes
in metabolism motility biofilm formation and virulence. Microbiology
157(Pt 11):3124-37.
Silva M, Bodor D, StellfoxM, Martins N, Hochegger H, Foltz D, Jansen LET.
(2011). Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle
Progression. Dev Cell 22(1):52-63.
Silva RF, Mendonca SCM, Carvalho LM, Reis AM, Gordo I, Trindade S, Dionisio
F. (2011). Pervasive Sign Epistasis between Conjugative Plasmids
and Drug-Resistance Chromosomal Mutations. PLOS GENETICS 7(7):Article
Number: e1002181
Soares MC, Oliveira RF, Ros AFH, Grutter A, Bshary R. (2011). Tactile stimulation
lowers stress in fish. Nature Communications 2: Article Number: 534.
Sousa A, Magalhães S, Gordo I. (2011). Cost of antibiotic resistance and
the geometry of adaptation. Molecular biology and evolution [Epub
ahead of print].
Sousa FL, Alves RJ, Pereira-Leal JB, Teixeira M, Pereira MM. (2011). A Bioinformatics
Classifier and Database for Heme-Copper Oxygen Reductases.
PLOS ONE 6(4): Art. Nº e19117.
Sousa S, Afonso N, Bensimon-Brito A, Fonseca M, Simoes M, Leon J, Roehl
H, Cancela ML, Jacinto A. (2011). Differentiated skeletal cells contribute
to blastema formation during zebrafish fin regeneration. Development
138(18):3897-3905.
Sousa VC, Beaumont MA, Fernandes P, Coelho MM, Chikhi L. (2011). Population
divergence with or without admixture: selecting models using an ABC
approach. Heredity (Edinb) [Epub ahead of print].
Su X, Qiu W, Gupta M Jr, Pereira-Leal JB, Reck-Peterson S, Pellman D. (2011).
Mechanisms Underlying the Dual-Mode Regulation of Microtubule Dynamics
by Kip3/Kinesin-8. Molecular Cell 43(5):751-763.
Szuts TA, Fadeyev V, Kachiguine S, Sher A, Grivich MV, Agrochao M, Hottowy
P, Dabrowski W, Lubenov EV, Siapas AG, Uchida N, Litke AM, Meister
M. (2011). A wireless multi-channel neural amplifier for freely moving animals.
Nature Neuroscience 14(2):263-269.
Tarafder AK, Wasmeier C, Figueiredo AC, Booth AE, Orihara A, Ramalho JS,
Hume A, Seabra MC. (2011). Rab27a Targeting to Melanosomes Requires
Nucleotide Exchange but not Effector Binding. Traffic 12(8):1056-66.
Tavares B, Dias PN, Domingos P, Moura TF, Feijó JA, Bicho A. (2011). Calciumregulated
anion channels in the plasma membrane of Lilium longiflorum
pollen protoplasts. The New Phytologist 192(1):45-60.
Tavares B, Domingos P, Dias PN, Feijó JA, Bicho A. (2011). The essential role
of anionic transport in plant cells: the pollen tube as a case study. Journal
of Experimental Botany 62(7):2273-98.
Teixeira V, Arede N, Gardner R, Rodriguez-Leon J, Tavares AT. (2011). Targeting
the hemangioblast with a novel cell type-specific enhancer. BMC
Developmental Biology 11(1):76.
Thorsteinsdóttir S, Deries M, Cachaço AS, Bajanca F. (2011). The extracellular
matrix dimension of skeletal muscle development. Developmental Biology
354(2):191-207.
140. Tomás AR, Certal AC, Rodríguez-León J. (2011). FLRT3 as a key player on
chick limb development. Developmental Biology 355(2):324-33.
IGC ANNUAL REPORT ‘11
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116

141.
142.
143.
144.
145.
146.
147.
148.
149.
150.
151.
152.
153.
Tsuji S, Cortesao C, Bram R, Platt J, Cascalho M. (2011). TACI deficiency impairs
sustained Blimp-1 expression in B cells decreasing long-lived plasma
cells in the bone marrow. Blood 118(22):5832-5839.
Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J,
Martinho RG, Gevaert K, Arnesen T. (2011). NatF Contributes to an Evolutionary
Shift in Protein N-Terminal Acetylation and Is Important for Normal
Chromosome Segregation. PLoS Genetics 7(7): e1002169.
Van de Ven C, Bialecka M, Neijts R, Young T, Rowland J, Stringer E, van
Rooijen C, Meijlink F, Novoa A, Freund J-N, Mallo M, Beck F, Deschamps
J. (2011). Concerted involvement of Cdx/Hox genes and Wnt signaling in
morphogenesis of the caudal neural tube and cloacal derivatives from the
posterior growth zone. Development 138(16):3451-3462.
Velez de Mendizabal N, Carneiro J, Sole RV, Goni J, Bragard J, Martinez-
Forero I, Martinez-Pasamar S, Sepulcre J, Torrealdea J, Bagnato F, Garcia-
Ojalvo J, Villoslada P. (2011). Modeling the effector - regulatory T cell crossregulation
reveals the intrinsic character of relapses in Multiple Sclerosis.
BMC Systems Biology 5 Article Number: 114.
Vicente MI, Mainen ZF. (2011). Convergence in the piriform cortex. Neuron
70(1):1-2.
Vilares I, Dam G, Kording K. (2011). Trust and Reciprocity: Are Effort and
Money Equivalent? PLOS ONE 6(2):e17113.
Vilares I, Kording K. (2011). Bayesian models: the structure of the world
uncertainty behavior and the brain. Annals of the New York Academy of
Sciences 1224(1):22-39.
Vilas-Boas F, Fior R, Swedlow JR, Storey KG, Henrique D. (2011). A novel reporter
of notch signalling indicates regulated and random notch activation
during vertebrate neurogenesis. BMC Biology 9: Article Number: 58.
Vinod PK, Freire P, Rattani A, Ciliberto A, Uhlmann F, Novak B. (2011). Computational
modelling of mitotic exit in budding yeast: the role of separase and
Cdc14 endocycles. Journal of the Royal Society Interface 8(61):1128-1141.
Xavier JM, Shafiee NM, Ghaderi F, Rosa A, Abdollahi BS, Nadji A, Shahram
F, Davatchi F, Oliveira SA. (2011). Association of mitochondrial polymorphism
m709G > A with Behcet's disease. Annals of the Rheumatic Diseases
70(8):1514-1516.
Winter O, Mohr E, Manz RA. (2011). Alternative cell types form a Multi-
Component-Plasma-Cell-Niche. Immunology Letters 141(1):145-146.
Wollenberg I, Agua-Doce A, Hernandez A, Almeida C, Oliveira V, Faro J,
Graca L. (2011). Regulation of the Germinal Center Reaction by Foxp3(+)
Follicular Regulatory T Cells. Journal of Immunology 187(9):4553-4560.
Zenclussen ML, Casalis PA, El-Mousleh T, Rebelo S, Langwisch S, Linzke N,
Volk H-D, Fest S, Soares MP, Zenclussen AC. (2011). Haem oxygenase-1 dictates
intrauterine fetal survival in mice via carbon monoxide. Journal of
Pathology 225(2):293-304.
154. Zenclussen ML, Jensen F, Rebelo S, El-Mousleh T, Casalis PA, Zenclussen AC.
(2011). Heme Oxygenase-1 Expression in the Ovary Dictates a Proper Oocyte
Ovulation Fertilization and Corpora Lutea Maintenance. American journal
of reproductive immunology [Epub ahead of print].
IGC ANNUAL REPORT ‘11
PUBLICATIONS
117

BOOK CHAPTERS
Cabrito TR, Remy E, Teixeira MC, Duque P, Sá-Correia I. (2011). Resistance to
herbicides in the model organisms Saccharomyces cerevisiae and Arabidopsis
thaliana: the involvement of multidrug resistance transporters in Herbicides and
Environment (ed A Kortekamp). Tech Vienna Austria pp 623-640.
Costa H, Correia S, Nascimento R, Parkhouse RM. (2011). Interferon the Cell Cycle
and Herpesvirus in Herpesviridae - A Look Into This Unique Family of Viruses.
Edited by George D Magel and Stephen Tyring. Tech Education and Publishing
(ISBN 978-953-51-0186-4)
Sepulveda N, Carneiro J. (2011), Repertoire dynamics of peripheral regulatory
and effector T cells competing for antigen presenting cells. Mathematical Models
and Immune Cell Biology (Editors: Lythe and Molina-Paris) Elsevier.
PROCEEDINGS
Luna B, Chaouiya C. (2011). Relating Formalisms for the Qualitative Modelling of
Regulatory Networks. 5th In Conf on Practical Applications of Computational
Biology & Bioinformatics (PACBB 2011) in Advances in Intelligent and Soft
Computing Vol 93 pp. 293-302.
Kolchinsky A, Rocha LM. (2011). Prediction and Modularity in Dynamical Systems.
Advances in Artificial Life Proceedings of the Eleventh European Conference
on the Synthesis and Simulation of Living Systems (ECAL 2011) Paris France
MIT Press pp. 423-430.
Marques-Pita M, Rocha LM. (2011) Schema Redescription in Cellular Automata:
Revisiting Emergence in Complex Systems. The 2011 IEEE Symposium on Artificial
Life at the IEEE Symposium Series on Computational Intelligence 2011
Paris France pp. 233-240.
IGC ANNUAL REPORT ‘11
PUBLICATIONS
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IGC ANNUAL REPORT ‘11
PUBLICATIONS
119

PRIZES AND HONOURS
INSTITUTO GULBENKIAN DE CIÊNCIA
Best Places to Work for Post-docs 2011 Award
The Scientist - Faculty of 1000's Magazine of the Life Sciences
Professional Merit Award
Oeiras Rotary Club (Portugal)
Honorary Membership of the Ordem de Sant'Iago da Espada
President of the Republic (Portugal)
IGC SCIENCE COMMUNICATION TEAM
Ciencia en Acción - Teaching Resources 1st Place
Ciencia en Acción (Spain)
IGC ANNUAL REPORT ‘11
PRIZES AND HONOURS
120

António Coutinho
Professional Merit Award
Oeiras Rotary Club (Portugal)
Miguel Soares
Roche Organ Transplantation Research Foundation (ROTRF) Recognition Prize
Recognising Excellence in Organ Transplantation Research
Seeds of Science - Life Science Award
Ciência Hoje and Ciência Viva (Portugal)
Miguel Godinho Ferreira
Gold Medal of Merit
Oeiras City Council (Portugal)
José Feijó
Gold Medal of Merit
Oeiras City Council (Portugal)
Tiago Carneiro
Best Paper Award
Portuguese Society for Human Genetics (Portugal)
Xin Jin and Rui Costa
Best Paper Award
Portuguese Society for Neuroscience and Bayer (Portugal)
Rui Costa
Elected Vice-President, Portuguese Society for Neuroscience
Nominated to the Editorial Board, Frontiers in Integrative Neuroscience
Florence Janody
Nominated to the Scientific Editorial Board, The Scientific World and PLoS ONE
Isabel Gordo
Nominated Associate Editor, Evolution
Nominated Review Editor, Fronteirs in Population and Evolutionary Genetics
Moises Mallo
Nominated to the Editorial Board, Developmental Dynamics
IGC ANNUAL REPORT ‘11
PRIZES AND HONOURS
121

BUDGET
OVERVIEW
TOTAL BUDGET 2011: €17.4million
EXTERNAL PUBLIC
(EUROPEAN COMMISSION, FCT, CITY COUNCILS, OTHERS)
€5.2million
CALOUSTE GULBENKIAN FOUNDATION
€9million
EXTERNAL PRIVATE
(CHAMPALIMAUD FOUNDATION, BILL & MELINDA GATES FOUNDATION, COMPANIES, OTHERS)
€3.2million
BREAKDOWN OF IGC EXPENDITURE 2011
TOTAL: €17.4million
€7million
€8.6million
PERSONELL
(STAFF & RESEARCHERS))
OPERATIONS
(NEW EQUIPMENT, FACILITY COSTS, ETC)
INFRASTRUCTURE
(BUILDING MAINTENANCE, REFURBISHMENTS)
€1.8million
EXTERNAL FUNDING
€2.2million
CALOUTE GULBENKIAN FOUNDATION
€6.4million
IGC ANNUAL REPORT ‘11
MAJOR FUNDING SOURCES
122

GRADUATE
TRAINING
AND
EDUCATION

PHD PROGRAMME
IN INTEGRATIVE
BIOMEDICAL SCIENCES
Thiago Carvalho Head
PhD in Immunology, Universidade do Porto, Portugal, 2003
The IGC's PhD Programme in Integrative Biomedical Sciences (PIBS) provides
a solid foundation in the life sciences, and exposes students to cutting edge
research, before they design and submit their independent research projects
under the guidance of Institute scientists. PIBS students are an international
group, hailing from many different educational backgrounds. During their academic
modules, students are taught by both IGC scientists and an international
faculty of leading scientists from around the world.
SUPPORT STAFF
Manuela Cordeiro (Secretary)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Calouste Gulbenkian Foundation, Portugal
Student life at the IGC is not restricted to the course modules, with several
workshops and courses available throughout the year, an abundance of guest
seminar speakers and meetings students themselves organise. PIBS represents
the continuation of a strong investment in graduate education at the IGC, dating
back to the first PhD programme, created in 1993. IGC alumni have not only been
personally successful, but over the past decade those who stayed or returned
to Portugal have dramatically reshaped the country’s research landscape. The
PIBS programme is supported by the Fundação para Ciência e Tecnologia and
the Calouste Gulbenkian Foundation.
STUDENTS IN 2011
Ana Rita Aires Portugal Evolutionary and Developmental Biology Universidade de Lisboa, Portugal
Ana M. Ribeiro Portugal Evolutionary and Developmental Biology Universidade de Lisboa, Portugal
Ana Stankovic Serbia Experimental Biomedicine University of Belgrade, Serbia
Irma Lasheras Spain Biology, Evolution, Biodiversity, and Conservation Leiden University, The Netherlands
Jaroslaw Surkont Poland Biotechnology Jagiellonian University, Poland
Maria Ines Pais Portugal Evolutionary and Developmental Biology Universidade de Lisboa, Portugal
Marta Marialva Portugal Evolutionary and Developmental Biology Universidade de Lisboa, Portugal
Ozhan Ozkaya Turkey Molecular Biology and Genetics Istanbul Technical University, Turkey
Rafal Gumienny Poland Biotechnology Jagiellonian University, Poland
Rômulo Areal Brazilian Oncology Research National Cancer Institute, Brazil
Sandra Tavares Portugal Molecular Biomedicine Universidade de Aveiro, Portugal
Sara Esteves Portugal Evolutionary and Developmental Biology Universidade de Lisboa, Portugal
COURSES IN 2011
History of Biological Concepts
3 - 7 October
Organiser: Thiago Carvalho (IGC, PT)
Faculty: Pietro Corsi (Oxford Univ., UK), Jonathan Howard (University of Cologne, DE),
Thiago Carvalho, Christen Mirth, Lars Jansen, José Pereira Leal and Joe Paton
(IGC, PT)
Molecular and Structural Biology
10 - 14 October
Organiser: Alekos Athanasiadis (IGC, PT)
Faculty: Reuben Harris (University of Minnesota, USA), Guillermo Montoya
(CNIO, ES), Manwlis Matzapetakis, Claudio Soares and Bruno Victor (ITQB, PT)
Inside the Cell
17 - 21 October
Organiser: Lars Jansen (IGC, PT)
Faculty: Niels Gehring, Bjoern Schumacher (University of Cologne, DE), Geneviève
Almouzni (CNRS Institut Curie, Paris, FR), Andrew Holland (UC Davis, USA), Rob
Wolthuis (The Netherland Cancer Institute, NL), Luísa Figueiredo (IMM, PT), Alekos
Athanasiadis, Lars Jansen and Miguel Godinho Ferreira (IGC, PT)
The PIBS classes of 2010 and 2011 with the IGC Director, António Coutinho.
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Cells to organisms I
24 - 28 October
Organiser: Thiago Carvalho (IGC, PT)
Faculty: Pierre Golstein (CIML, FR), Mathieu Molet (Université Pierre et Marie
Curie, FR), Kevin Foster (Oxford University, UK), Etienne Danchin (Université
Paul Sabatier - Toulouse III, FR), Élio Sucena, Thiago Carvalho, Karina Xavier
and Filipe Borges (IGC, PT)
Cells to Organisms II - Limb Development
31 October - 4 November
Organiser(s): Diogo Castro and Joaquin Léon (IGC, PT)
Faculty: Malcolm Logan (MRC London, UK), Juan Hurlé (Universidad de Cantabria,
ES), James Sharpe (CRG Barcelona, ES), Florence Janody, Kohtaro Tanaka,
Diogo Castro (IGC, PT), Solveig Thorstensdottir (Universidade de Lisboa, PT),
Joaquin Rodriguez-Leon (IGC, PT/Extremadura University, ES)
Statistics
7- 11 November
Organiser: Jorge Carneiro (IGC, PT)
Faculty: Jorge Carneiro (IGC, PT)
Genetic Models
14 - 18 November
Organiser: Vitor Barbosa (IGC, PT)
Faculty: Jesús Aguirre (Universidad Nacional Autonóma de México, MX), Fernando
Roch (Univ. Toulouse, FR), Karen Liu (Kings College London, UK), Miodrag
Grbic (Univ. Logroño, ES), Thiago Carvalho, Filipa Alves, Sara Carvalho, Ana
Borges, Clara Reis, Moises Mallo, Elena Baena, Ana Mena (IGC, PT)
Evolution
21 - 25 November
Organiser: Isabel Gordo (IGC, PT)
Faculty: Brian Charlesworth (University of Edinburgh, UK), Olivier Tenaillon
(INSERM, FR), Michael Turelli (UC Davis, USA), Henrique Teotónio, Gabriela
Gomes (IGC, PT)
Evolution, Development and Ecology
28 November - 2 December
Organiser(s): Patricia Beldade, Élio Sucena and Christen Mirth (IGC, PT)
Faculty: Atanasios Pavlopoulos (University of Cambridge, UK), Christian Braendle
(Université de Nice, FR), Johannes Jaeger (EMBL/CRG, ES), Patricia Beldade, Élio
Sucena, Christen Mirth (IGC, PT)
Instrumentation
5 - 10 December
Organiser: Nuno Moreno (IGC, PT)
Faculty: Andrew Riddell (EMBL, DE), Jan Willem Brost (JWB, NL), Nuno Moreno,
Emilio Gualda, Gabriel Martins, Pedro Almada, Jorg Becker (IGC, PT), José Rino
(IMM, PT)
Neurobiology
12 - 21 December
Organiser: Michael Orger, Luisa Vasconcelos (CNP, PT)
Faculty: Rui Costa, Zachary Mainen, Adam Kampff, Michael Orger, Alfonso
Renart, Inbal Israely, Megan Carey, Carlos Ribeiro, Florian Dehmelt, Magor
Lorincz, Luísa Vasconcelos, Susana Lima, Joe Paton (CNP, PT)
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PHD PROGRAMME
IN COMPUTATIONAL
BIOLOGY
Jorge Carneiro Head
PhD in Biomedicine, Universidade do Porto, 1997
PI of Quantitative Organism Biology Group
The PhD Programme in Computational Biology (PDBC) is a pilot graduate programme
that aims to create a critical mass of researchers in computational biology,
to act as future leaders in the field. To this end it operates in close association with
its twin initiative, the Collaboratorium in Computational Biology. It is sponsored
by the Portuguese Ministry for Science and Technology, the Calouste Gulbenkian
Foundation, and Siemens Portugal SA.
The PDBC was launched in 2005, has a definitive lifespan and was planned to
educate four generations of 12 students per year. Education is organised as a
four-year programme divided into a year of full-time courses, workshops and
projects, covering the main aspects of computational biology from the biological,
computational, mathematical, chemical and physical points of view, and
three years of research training in a recognised laboratory anywhere in the
world, including Portugal. Non-national citizens were accepted but their research
training was restricted to Portuguese research labs. The choice of laboratory
was left to the student but met the standards set by the Programme
Direction.
SUPPORT STAFF
Cláudio Soares (ITQB, Deputy Director)
Manuela Cordeiro (Administrative Assistant)
FUNDING
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Siemens Portugal, SA
Calouste Gulbenkain Foundation, Portugal
PT Foundation, Portugal
Fundação Luso-Americana para o Desenvolvimento (FLAD), Portugal
Fundação para a Computação Científica Nacional (FCCN), Portugal
The PDBC has come of age and all 41 students are carrying out their research
training in labs in Europe and beyond, and eight (Inês de Jesus, José Cruz, Nuno
Mendes, Marcio Mourão, Sara da Silva, Pedro Monteiro, Bruno Correia, and Luis
Figueiredo) have obtained their doctoral degree. Information on the individual
students, and completed theses, can be found on the programme’s website.
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INDP - INTERNATIONAL
NEUROSCIENCE
DOCTORAL PROGRAMME
Zachary Mainen Head
PhD in Neurosciences, University of California, San Diego, 1995
PI of Systems Neuroscience Group
The INDP aims at providing students with a broad and integrative education
in neuroscience with a focus on the neuronal and circuit basis of behaviour.
A main goal of the programme is to foster and encourage active participation,
independence and critical thinking on the part of the students. In the first
year of the programme, students attend courses structured as modules lasting
one or a few weeks, which cover basic topics in contemporary neuroscience
such as basic cellular and synaptic physiology, sensation and action and cognitive
neuroscience. Quantitative approaches are emphasised and students also
receive background courses on basic biology, mathematics and programming.
The next three years are dedicated to research on a specific topic leading to
a PhD thesis. No previous background in neuroscience is required, but candidates
with a background in biology or quantitative disciplines are encouraged
to apply.
SUPPORT STAFF
Alexandra Piedade (Assistant)
Alfonso Renart, PhD (Coordinator)
FUNDING
Champalimaud Foundation, Portugal
Fundação para a Ciência e a Tecnologia (FCT), Portugal
Calouste Gulbenkian Foundation, Portugal
STUDENTS IN 2011
André Luzardo Brazil Psychobiology Universidade de São Paulo, Ribeirão Preto, Brazil
Jacques Bourg France Electrical Engineering Inst. National des Sciences Appliquées de Lyon, France
Jens Bierfeld Germany Biology University of Konstanz, Konstanz, Germany
João Afonso Portugal Clinical Psychology Inst. Superior Psicologia Aplicada, Lisboa, Portugal
Joaquim Jacob Portugal Neuroscience Fac. Medicina da Universidade de Lisboa, Portugal
Ricardo Zacarias Portugal Evolutionary and Develop. Biology Fac. Ciências da Univ. de Lisboa, Portugal
Roberto Medina Mexico Mathematics University of Illinois at Urbana-Champaign, USA
Silvana Araújo Portugal Psychopharmacology University of Nottingham, United Kingdom
Sofia Soares Portugal Human Biology and Environment Fac. Ciências da Universidade de Lisboa, Portugal
Luis Moreira Portugal Ecology Universidade de Coimbra, Portugal
COURSES IN 2011
Introduction
10 - 14 January
Organiser(s): Susana Lima, Marta Moita, Carlos Ribeiro (IGC/FC , PT)
Faculty: Susana Lima (IGC/FC), Marta Moita (IGC/FC), Carlos Ribeiro (IGC/FC , PT)
Introduction: Evolution
17 - 21 January
Organiser(s): Susana Lima, Marta Moita, Carlos Ribeiro and Luisa Vasconcelos
(IGC/FC, PT)
Faculty: Susana Lima, Marta Moita, Carlos Ribeiro, Luisa Vasconcelos (IGC/FC,
PT), Chris Braun (Hunter College, City University of New York, USA)
Cellular Physiology
24 - 28 January
Organiser(s): Joshua Dudman (Howard Hughes Medical Institute, USA)
Faculty: Alex Reyes (Center for Neural Science - New York University, USA)
Circuits
31 January - 4 February
Organiser(s): Michael Orger (FC, PT)
Faculty: Ruben Portugues (Department of Molecular and Cellular Biology, Harvard
University, USA)
Plasticity
7 - 11 February
Organiser(s): Inbal Israeli (IGC/FC, PT)
Faculty: Steve Kushner (Erasmus MC University Medical Center Rotterdam, The
Netherlands)
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Learning
14 - 18 February
Organiser(s): Megan Carey (FC, PT)
Faculty: Sam Sober (School of Biology Emory University Atlanta, USA)
Metabolism
28 February - 4 March
Organiser(s): Carlos Ribeiro (IGC/FC, PT)
Faculty: Matt Piper (University College London, UK)
Sensory & Motor
7 - 11 March
Organiser(s): Carlos Ribeiro (IGC/FC, PT), Eugenia Chiappe (Howard Hughes
Medical Institute, USA), Michael Orger (FC, PT)
Faculty: Eugenia Chiappe (Howard Hughes Medical Institute, USA)
Movement into Action
14 - 18 March
Organiser(s): Rui Costa (IGC/FC, PT)
Faculty: José Carmena (Department of Electrical Engineering and Computer Sciences,
University of California, Berkeley, USA), Joe Mcintyre (CNRS Laboratoire
de Physiologie de la Perception et de l'Action - College de France, France)
Experimental Approaches - Basic
21 - 25 March
Organiser(s): Adam Kampff, Michael Orger (FC, PT), Florian Engert (Harvard University,
USA)
Faculty: Adam Kampff, Michael Orger (FC, PT)
Experimental Techniques–Advanced
28 March - 1 April
Organiser(s): Adam Kampff, Michael Orger (FC, PT), Florian Engert (Harvard University,
USA)
Faculty: Florin Albeanu (Cold Spring Harbor Laboratory, USA)
Projects
4 - 15 April
Faculty: Adam Douglass (Harvard University, USA), Janet Iwasa (Department of
Cell Biology - Harvard Medical School, USA)
Computational Approaches
26 - 29 April
Organiser(s): Christian Machens, Alfonso Renart (FC, PT)
Faculty: Sophie Deneve (Départment d'Etudes Cognitives (DEC), Ecole Normale
Supérieure), John Hertz (Niels Bohr Institute, Denmark)
Vision to Decision
9 - 13 May
Organiser(s): Joe Paton (IGC/FC, PT)
Faculty: Gabe Murphy (Howard Hughes Medical Institute, USA) Virginia Flanigan
(Ludwig-Maximilians-Universität - Department of Neurology, Germany), Brian
Lau (Dept of Neuroscience Columbia University, USA), Kenway Louie (Center
for Neural Science, New York University, USA) David Freedman (Department of
Neurobiology, The University of Chicago, USA)
Consciousness
23 - 27 May
Organiser(s): Zachary Mainen (IGC/FC, PT)
Faculty: Peter Mandik (Department of Philosophy, William Patterson University, USA)
Social Interactions
23 - 27 May
Organiser(s): Marta Moita, Susana Lima (IGC/FC, PT)
Faculty: Regina Sullivan (Department of Zoology, University of Oklahoma, USA)
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Extroduction
30 May - 3 June
Organiser(s): Élio Sucena (IGC , PT)
History of Biological Concepts
3 - 7 October
Organiser: Thiago Carvalho (IGC, PT)
Faculty: Pietro Corsi (Faculty of History, University of Oxford, UK), Jonathan Howard
(Department of Cell Genetics, Institute for Genetics, University of Cologne,
Germany), Thiago Carvalho, Chrirsten Mirth, Lars Jansen, José Pereira Leal (IGC,
PT), Joe Paton (IGC/FC, PT)
Molecular and Structural Biology
10 - 14 October
Organiser: Alekos Athanasiadis (IGC, PT)
Faculty: Niels Gehring (Institute for Genetics, University of Cologne, Germany),
Guillermo Montoya (Spanish National Cancer Research Centre, Spain), Manwlis
Matzapetakis, Claudio Soares, Bruno Viktor (ITQB, Portugal)
Inside the Cell
17 - 21 October
Organiser: Lars Jansen (IGC, PT)
Faculty: Niels Gehring (Institute for Genetics, University of Cologne, Germany),
Bjoern Schumacher (CECAD Cologne at the Institute for Genetics, University of
Cologne, Germany), Geneviève Almouzni (Nuclear Dynamics and Genome Plasticity
Unit, Curie Institute, France), Andrew Holland (Ludwig Institute for Cancer Research,
USA), Rob Wolthuis (The Netherlands Cancer Institute, The Netherlands)
Cells to Organisms I
24 - 28 October
Organiser: Thiago Carvalho (IGC)
Faculty: Mathieu Molet (Université Pierre et Marie Curie, France), Kevin Foster
(Department of Zoology, Oxford University, UK), Pierre Golstein (Centre
d'Immunologie de Marseille-Luminy, France), Etienne Danchin (Directeur de Recherche
CNRS Head of the Laboratoire Evolution et Diversité Biologique Univ.
Paul Sabatier, France)
Cells to Organisms II - Limb Development
31 October - 4 November
Organiser(s): Diogo Castro, Joaquin Léon (IGC, PT)
Faculty: Malcolm Logan (National Institute for Medical Research, UK), Juan
Hurlé (University of Extremadura, Spain), James Sharpe (EMBL - Center for
Genomic Regulation, Spain), Diogo Castro, Joaquin Léon, Florence Janody (IGC,
PT), Solveig Thorsteinsdottir (FCUL, PT)
Statistics
7 - 11 November
Organiser: Jorge Carneiro (IGC, PT)
Faculty: Jorge Carneiro (IGC, PT)
Genetic Models
14 - 18 November
Organiser: Vitor Barbosa (IGC, PT)
Faculty: Jesús Aguirre (Univ. Nacional Autónoma de México, México), Fernando
Roch (University of Toulouse, France), Karen Liu (King’s College London, UK),
Miodrag Grbic (University of Western Ontario, Canada), Thiago Carvalho, Filipa
Alves, Sara Carvalho, Ana Borges, Clara Reis, Moises Mallo, Elena Baena, Ana
Mena (IGC, PT)
Evolution
21 - 25 November
Organiser: Isabel Gordo (IGC, PT)
Faculty: Brian Charlesworth (University of Edimburgh, UK), Olivier Tenaillon
(Universite de Paris VII, France), Michael Turelli (University of California, Davis,
USA), Henrique Teotónio, Gabriela Gomes (IGC, PT)
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Evolution, Development and Ecology
28 November - 2 December
Organiser(s): Patricia Beldade, Élio Sucena, Christen Mirth (IGC, PT)
Faculty: Atanasios Pavlopoulos (University of Cambridge, UK), Christian Braendle
(Université de Nice, France), Johannes Jaeger (EMBL - Center for Genomic
Regulation, Spain), Patricia Beldade, Élio Sucena, Christen Mirth (IGC, PT)
Instrumentation
5 - 10 December
Organiser: Nuno Moreno (IGC, PT)
Faculty: Andrew Riddell (Head of Flow Cytometry Core Facility, EMBL, Germany),
Jan Willem Brost (JWB, The Netherlands), Nuno Moreno, Emilio Gualda, Gabriel
Martins, Pedro Almada, Jorg Becker (IGC, PT), José Rino (IMM, PT)
Neurobiology
12 - 19 December
Organiser(s): Michael Orger (FC, PT), Luisa Vasconcelos (FC/IGC, PT)
Faculty: Rui Costa, Zach Mainen, Inbal Israeli, Carlos Ribeiro, Susana Lima, Luisa
Vasconcelos), Joe Paton (IGC/FC, PT), Michael Orger, Alfonso Renart, Adam
Kampff (FC, PT), Magor Lorincz (postdoctoral fellow, IGC/FC), Florian A. Dehmelt
(PhD student, FC)
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PROGRAMME
FOR ADVANCED MEDICAL RESEARCH -
DOCTORAL PROGRAMME FOR PHYSICIANS
António Coutinho Head
PhD in MD, Medical Microbiology, Karolinska Institute, Stockholm, 1974
Director of IGC
The Programme for Advanced Medical Education is a Doctoral Programmme for
physicians, supported by the Gulbenkian and Champalimaud Foundations, the
Ministry of Health and the Fundação para a Ciência e a Tecnologia, Portugal. The
4th edition is also sponsored by Espírito Santo Saúde and José de Mello Saúde.
The Programme targets highly motivated clinicians who wish to acquire a strong
scientific background as a basis for excellence in medical research and clinical
practice. The programme selects 10 students per year, either on a full time (Specialists
and Interns) or part-time basis (Interns).
SUPPORT STAFF
Francisca Moura (FCG)
Manuela Cordeiro (IGC)
FUNDING
Calouste Gulbenkian Foundations, Portugal
Champalimaud Foundation, Portugal
Ministry of Health, Portugal
Fundação para a Ciência e a Tecnologia, Portugal.
Espírito Santo Saúde, Portugal
José de Mello Saúde, Portugal
Students attend graduate courses by an international faculty, followed by thesis
work at national or international institutions. Graduate courses take place
at leading Portuguese biomedical research institutions: Instituto Gulbenkian
de Ciência; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa;
IPATIMUP, Porto; Faculdade de Ciências Médicas, Universidade Nova de Lisboa;
Faculdade de Medicina da Universidade do Porto.
STUDENTS IN 2011
Mariana Machado
Ana Sofia Duarte António
Maria Ester Pereira
Mafalda Santos Barbosa
Branca Isabel Pereira
Liliana Pereira
João Nuno Duarte
Ana Catarina Castro
José Miguel Ferreira
Specialist in Gastroenterology, Hospital Santa Maria, Lisbon
Specialist in Neurology, Hospital D. Estefânia, Lisbon
Specialist in Neurology, Hospital Santo António, Porto
Specialist in Genetics, Centro de Genética Médica Jacinto Magalhães, Lisbon
Specialist in Infectious Diseases, Hospitais da Universidade de Coimbra
Intern in Ophtalmology, Instituto Gama Pinto, Lisbon
Intern in Maxillofacial Surgery, Hospitais da Universidade de Coimbra
Intern in Pshychiatry, Hospital Júlio de Matos, Lisbon
Intern in Radiotherapy, Hospital Santa Maria, Lisbon
COURSES IN 2011
Gene Expression
27 September - 7 October
Organiser(s): João Ferreira (IMM/FML, PT)
Faculty: João Ferreira, Francisco Enguita (IMM/FML, PT), Thiago Carvalho, Joana
Cardoso (IGC, PT), Margarida Gama-Carvalho, Carlos Farinha (FCUL, PT), Patrick
Varga-Weisz (Babraham Institute, Cambridge, UK), Maria Mota, Leonor Saúde,
Luis Graça, Bruno Santos (IMM/FML, PT)
Molecular and Structural Biology
10 - 14 October
Organiser: Alekos Athanasiadis (IGC, PT)
Faculty: Reuben Harris (University of Minnesota, USA), Guillermo Montoya (CNIO, ES),
Manwlis Matzapetakis, Claudio Soares, Bruno Victor (ITQB, PT)
Cell Cycle, Cytoskeleton & Disease
24 - 28 October
Organiser: Mónica Bettencout-Dias (IGC, PT)
Faculty: Helder Maiato (IBMC, PT), Clare Waterman Storer (NIH, USA), Edgar
Gomes (UMR S 787, Inserm/Pitie-Salpétrière, Université Paris VI, FR), Fanni
Gergely (Cambridge Research Institute, UK), Tim Miller (Washington University
School of Medicine, USA), Monica Bettencourt-Dias, Miguel Godinho-Ferreira,
Florence Janody, Lars Jansen (IGC, PT)
Medical Statistics
31 October - 5 November
Organiser: Armando Teixeira Pinto (FMUP, PT)
Faculty: Armando Teixeira Pinto (FMUP, PT)
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Medical Statistics
7 - 11 November
Organiser: Isabel Santos Silva (LSHTM, UK)
Faculty: Valerie McCormack (International Agency for Research on Cancer, Lyon,
FR), Isabel dos Santos Silva (LSHTM, UK)
Medical Epidemiology
14 - 18 November
Organiser: José Pereira Leal (IGC, PT)
Faculty: James Brenton (Cancer Research, UK), Yu-Hui Rogers (J. Craig Venter
Institute, USA), Nuno Palma (BIAL, PT), Francois Balloux (Imperial College, UK),
Ana Teresa Freitas (INESC-ID/IST, PT), Isabel Gordo, Jorge Carneiro, Sofia Braga,
Joana Cardoso, Marie Bonnet , Jose Pereira-Leal (GC, PT), Catarina Coreia
(IGC & INSRJ, PT)
Development Biology
21 - 25 November
Organiser: Moises Mallo (IGC, PT)
Faculty: Moises Mallo (IGC, PT), Miguel Manzanares (CNIC, ES), Malcolm Logan
(NIMR, UK), Andreas Kispert (School of Medicine Hannover, DE), Jacqueline Deschamps
(Hubrecht Institute, NL), Domingos Henrique ((FMUL/IMM, PT), Sérgio
Dias (IPO Lisboa, PT)
Genetics
28 November - 02 December
Organiser: Carlos Penha-Gonçalves (IGC, PT)
Faculty: Taane Clark, Susana Campino (Wellcome Trust Sanger Institute, UK),
Nuno Sepúlveda (LSHTM, UK), Lounes Chicki, Isabel Marques, Carlos Penha-Gonçalves,
Inês Rolim (IGC, PT), Astrid Vicente(INSA, PT), Sofia Oliveira (IMM, PT),
Ricardo Fernandes (FMUL, PT)
Pathogens & Hosts
5 - 9 December
Organiser: Adriano Henriques (ITQB/UNL, PT)
Faculty: Adriano Henriques, Luis Jaime Mota (ITQB/UNL, PT), Karina Xavier
(ITQB/UNL & IGC, PT)
Evolution and Medicine
12 - 14 December
Organiser: Stephen Stearns (Yale Univ., USA)
Faculty: Steven Stearns (Yale University, USA), and Jacob Koella (Imperial College
London, UK)
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GTPB - THE GULBENKIAN
TRAINING PROGRAMME
IN BIOINFORMATICS
Pedro Fernandes Head
Head of Portuguese Bioinformatics Centre
The GTPB provides practical skills in Bioinformatics. The objective is to deliver
those skills with high efficiency and as much autonomy of usage as possible. It
consists of short, intensive training courses, held in a specialised training room,
installed afresh in February 2011. The courses are taught and fully documented
in English. The target audience varies slightly with the course themes. The majority
of the participants are Biologists in the PhD project preparation phase.
STUDENTS IN 2011
In 2011, 241 students attended the GTPB training programme, including 40 from
foreign institutions. Forty seven students are at the IGC, and 86 are in research
groups at ITQB/IBET (partner institutes of the Associated Laboratory).
COURSES IN 2011
All courses were organised by Pedro Fernandes.
GACT11 - Genetic Architecture of Complex Traits
19 - 21 January
Faculty: Arcadi Navarro, Hafid Laayouni (Universtat Pompeu Fabre, Barcelona, ES)
MDA11 - Massive Data Analysis(using Babelomics)
21 - 23 February
Faculty: Joaqui Dopazo, Javier Santoyo-Lopez (Centro de Investigacion Principe
Felipe, Valencia, ES)
AFADM11 - Automatic Functional Annotation and Data Mining
24 - 25 February
Faculty: Stefan Goetz, Javier Santoyo-Lopez (Centro de Investigacion Principe
Felipe, Valencia, ES)
IB11 - Introductory Bioinformatics
28 March - 1 April
Faculty: David Phillip Judge (Cambridge University, UK), Phil Cunningham (Kings
College, London, UK), Pedro Fernandes (IGC, PT)
MAPS11 - Model-based Inference of Population Structure
4 - 8 April
Faculty: Mark Beaumont (University of Bristol, UK), Lounès Chikhi (IGC, PT),
Bárbara Parreira (IGC, PT)
MEPA11 - Molecular Evolution, Phylogenetics and Adaptation
11 - 15 April
Faculty: Hernan Dopazo, François Serra (Centro de Investigacion Principe Felipe,
Valencia, ES)
BPB11 - Bioinformatics using Python for Biologists
2 - 6 May
Faculty: Allegra Via, Fabrizio Ferrè (“La Sapienza”, IT)
RNA11 - RNA Bioinformatics
9 - 13 May
Faculty: Anton Enright (EBI, UK), Lars Barquist (Sanger Institute, UK)
NGSDM11 - NGS Data Management
26 - 27 May
Faculty: Matthias Haimel (EBI, UK), David Phillip Judge (Cambridge University, UK)
A course held in the new Bioinformatics Training Room. Interaction between an
instructor and participants.
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HGP11 - Hunting for Genes and Promoters
27 - 30 June
Faculty: Alexander Kel (GeneXplain GmbH, DE), Enrique Blanco (Universitat de
Barcelona, ES)
BBWA11 - Building Bioinformatics Web Applications
4 - 7 July
Faculty: David Leader, Richard Cooper (University of Glasgow, UK)
KDMC11 - Knowledge Discovery and Management in Chemoinformatics
12 - 15 July
Faculty: Alexey Lagunin, Alexey Zakharov (Institute of Biomedical Chemistry of
Rus. Acad. Med. Sci., RU)
MDARB11 - Microarray Data Analysis usingR and Bioconductor
5 - 9 September
Faculty: Oscar Rueda, Benilton Carvalho (Cambridge University, UK), Ana Rita
Grosso (Instituto de Medicina Molecular, PT)
PA11 - Pathway Analysis and Modelling of Biological Networks
19 - 20 October
Faculty: Christoph Wierling (Max Plank Institute, Berlin, DE), Roman Zubarev
(Karolinska Institutet, SE)
BFB11 - Biostatistical Foundations in Bioinformatics
24 - 28 October
Faculty: Antónia Turkman (Faculdade de Ciências da Universidade de Lisboa, PT),
Carina Silva Fortes (Escola Superior de Tecnologias da Saúde de Lisboa, PT)
IB11A - Introductory Bioinformatics, 2nd course
12 - 16 December
Faculty: David Phillip Judge (Cambridge University, UK), Phil Cunningham (Kings
College, London, UK), Pedro Fernandes (IGC, PT)
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THESES
MSc THESES
Sofia Pereira
Development of models to determine dynamic DNE expression in vivo to aid
resolution of sialic acid dysfunction associated with Hereditary Inclusion Body
Myopathy
Universidade de Trás-os-Montes e Alto Douro, Portugal
February 2011
Inês Pais
Identification and comparison of laboratory and wild caught Drosophila gut
microbiota
Faculdade de Ciências, Universidade de Lisboa, Portugal
October 2011
Pedro Silva
Supervised and unsupervised spermatozoa detection, classification and tracking
in imaging data
Faculdade de Ciências, Universidade de Lisboa, Portugal
October 2011
Andreia Cunha
Hox genes and the patterning of the axial skeleton
Universidade de Lisboa, Portugal
November 2011
Emanuel Costa
Viral modulation of interferon (IFN) responses to African swine fever virus (ASFV)
Universidade de Lisboa, Portugal
December 2011
Isa Pais
Genetic diversity in a little known Lemur species from the North of Madagascar
(Microcebus tavaratra)
Faculdade de Ciências, Universidade de Lisboa, Portugal
December 2011
Pedro dos Santos Lopes
Quantitative analysis of Bicyclus anynana‘s eyespot wing pattern images
Faculdade de Ciências, Universidade de Lisboa, Portugal
December 2011
PhD THESES
Tânia Vinagre
Hox genes control the specification of global vertebral domains
Universidade Nova de Lisboa, Portugal
January 2011
Ana Barbara Santos
Anionic currents in pollen grain protoplasts from Arabidopsis thaliana and Lilium
longiflorum
Universidade de Lisboa, Portugal
June 2011
Raquel Antunes
Neural mechanisms of stimulus generalisation in auditory fear conditioning
Universidade Nova de Lisboa, Portugal
July 2011
Ana Rita da Costa
Mitosis and N-terminal acetylation
Universidade Nova de Lisboa, Portugal
September 2011
Raquel Carvalho
Functional and molecular characterisation of SR45, a plant-specific splicing factor
involved in sugar and stress signaling in Arabidopsis thaliana
Universidade Nova de Lisboa, Portugal
November 2011
Ines Cunha Ferreira
Regulation of PLK4 levels and activity to ensure centriole number control
Universidade Nova de Lisboa, Portugal
December 2011
IGC ANNUAL REPORT ‘11
THESES
135

SEMINARS
WORKSHOPS
AND
MEETINGS

SEMINARS AT THE IGC
JANUARY 2011
DATE SPEAKER AFFILIATION TITLE
05.01 Lucien Aarden Sanquin Blood Supply Foundation, Holland Immune responses to therapeutic monoclonal
antibodies
06.01 Michael Mendes Sloan-Kettering Institute, USA Synaptic plasticity in the mouse spinal reflex circuit
11.01 Patrícia Beldade IGC, Portugal On the origin and diversification of novel traits:
old genes, new tricks
12.01 Didier Faustino Bureau des Mésarchitectures Don’t trust architects
13.01 Carol-Anne Martin University of Edinburgh, UK Understanding human brain size: centrosomes,
kinetochores and chromosomes
14.01 Bjoern Schumacher University of Cologne, Germany Genome instability in ageing and longevity
17.01 Jean-René Huynh Curie Institute, France Aurora-B and Survivin regulate the germline stem
cell lineage in Drosophila
18.01 Vitor Barbosa IGC, Portugal Surveillance of transcription during meiosis
modulates polarity of Drosophila oocytes
20.01 Corine Schoebel Dept. of Aquatic Ecology & Institute Host-parasite interactions in Daphnia
of Integrative Biology, ETH Zurich
- the role of variable environments
20.01 Erida Gjini Univ. of Glasgow, UK Bridging between parasite genomic data
and population processes:
Trypanosome dynamics and the VSG archive
21.01 Christopher Braun City University of New York, USA The evolution of a behavioural repertoire:
Jamming and jamming avoidance in weaklyelectric
fishes with a pulse discharge
21.01 João Sollari-Lopes CCMAR, Universidade do Algarve, Portugal Co-estimation of recombination and molecular
adaptation by approximate Bayesian computation
24.01 Sheila Vidal IGC, Portugal FCT R&D Projects in all Scientific Domains 2010.
How to apply?
26.01 Roberto Keller, IGC, Portugal (Post-doc seminar) Flapping wings and strong heads:
novel structures in queen and worker ants
26.01 Luciana Moraes IGC, Portugal (Post-doc seminar) Parasite sequestration in murine model
for pregnancy-associated malaria
26.01 Ana Cristina Borges IGC, Portugal (Post-doc seminar) Tight Junction components:
novel players in Epithelial Morphogenesis?
26.01 Ana Catarina Afonso IGC, Portugal (Post-doc seminar) Ion dynamics during fin regeneration in zebrafish
26.01 Ana Mena IGC, Portugal (Post-doc seminar) Animals in research: guidelines and awareness
27.01 Sheila Vidal IGC, Portugal FCT R&D Projects in all Scientific Domains 2010.
How to apply?
28.01 Dirk Bumann University of Basel, Switzerland Salmonella-host interactions in infected tissues
IGC ANNUAL REPORT ‘11
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137

FEBRUARY 2011
DATE SPEAKER AFFILIATION TITLE
01.02 Luis Teixeira IGC, Portugal Drosophila anti-viral immunity
01.02 Greenfield Sluder University of Massachusetts Medical School, USA Life after troubled mitosis: what happens
after cleavage fails or prometaphase is too long
02.02 Max Cooper Emory University, USA Evolution of lymphocyte-based adaptive immunity
08.02 Luis Rocha IGC, Portugal The complex systems approach to modelling
biochemical regulation and organisation
09.02 Geert Kops University Medical Center Utrecht, The Netherlands Maintaining genomic stability:
how mitotic kinases regulate chromosome
segregation
10.02 Steve Kushner University Medical Center Rotterdam, The Netherlands Selection of neuronal ensembles during
fear learning
11.02 Sarah Teichmann University of Cambridge, UK A quantitative view of gene expression levels
14.02 Luciano Adorini Intercept Pharmaceuticals, Corciano (Perugia), Italy Farnesoid X Receptor agonists in the treatment
of autoimmune diseases
15.02 José Feijó IGC, Portugal Pollen tube research at the IGC:
still growing after all these years
15.02 Maria Helena Goldman FFCLRP University of São Paulo, Brazil Sci1, a tissue-specific cell cycle regulator
that controls stigm/style development
17.02 Pedro Batista Stanford University, USA Characterisation of a Argonaute-related
small RNA pathways in C. elegans
18.02 Bruno Silva-Santos IMM, Portugal Caring for a minority:
gamma-delta T cell differentiation and activation
in mice and men
21.02 Leila Laredj Swiss Institute for Experimental Research PML nuclear bodies, the adeno-associated virus
in Cancer (ISREC), Switzerland
and the innate immune response
22.02 Moisés Mallo IGC, Portugal Hox genes and the ribs: an old relationship
with many faces
25.02 Pierre Golstein Centre de Immunologie Marseille-Luminy, France Autophagic cell death in the Dictyostelium model
IGC ANNUAL REPORT ‘11
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138

MARCH 2011
DATE SPEAKER AFFILIATION TITLE
01.03 Constantin Fesel IGC, Portugal Lupus and autoimmune repertoires
03.03 Ana Margarida Sousa IGC, Portugal (Post-doc seminar) Effects of synonymous (silent?) mutations
03.03 Maria Teresa Portes IGC, Portugal (Post-doc seminar) Investigating spatio-temporal causalities between
ion dynamics and growth in pollen tubes:
establishing the oscillations phase relationship
and their molecular bases
03.03 Álvaro Ferreira IGC, Portugal (Post-doc seminar) Antiviral immunity in Drosophila
03.03 Tiago Carneiro IGC, Portugal (Post-doc seminar) Checkpoint inhibition at fission yeast telomeres
03.03 Sílvia Correia IGC, Portugal (Post-doc seminar) Evasion of interferon responses by African
Swine Fever Virus
04.03 Ignácio Rubio Max Planck Institute for Developmental Biology, Small RNA networks with major roles in plant
Germany
development
11.03 Denis Duboule University of Geneva, Switzerland Understanding the mammalian regulatory
genome during development; of deserts
and archipelagos
15.03 Jocelyne Demengeot IGC, Portugal Sweetbread, indeed
17.03 Benedicte Sanson Univ. of Cambridge, UK Mechanisms of morphogenesis in early embryos
17.03 Pavel Tomancak Max Planck Institute of Molecular Cell Biology Gene expression divergence recapitulates
and Genetics, Germany
the developmental hourglass
17.03 Norbert Perrimon Harvard Medical School, USA Tissue and physiological homeostasis in Drosophila
18.03 Casper C. Hoogenraad Erasmus Medical Center, Rotterdam, The Netherlands Cytoskeletal organisation and polarised transport
in neurons
22.03 José Pereira-Leal IGC, Portugal New bioinformatics tools for evolutionary
cell biology
29.03 Jorg Becker IGC, Portugal Small RNA activity in the Arabidopsis male germline
30.03 Patricia Brito IGC, Portugal (Post-doc seminar) The importance of AI-2 mediated quorum sensing
for Escherichia coli fitness
30.03 Lea Zinck IGC, Portugal (Post-doc seminar) Development of a behavioural paradigm
to study the neuronal basis of social preferences
and mate choice in mice
30.03 Inês Conceição IGC, Portugal (Post-doc seminar) Genomic sequence around butterfly wing
development genes
30.03 Daniela Brito IGC, Portugal (Post-doc seminar) Plk4 activity: timing it rightly
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
139

APRIL 2011
DATE SPEAKER AFFILIATION TITLE
01.04 Ehab Abouheif McGill University, Canada Attempting to synthesize environment,
development, and evolution through the study
of winged and wingless castes in the hyperdiverse
ant genus Pheidole
05,04 Rui Martinho IGC, Portugal Spliceosome many faces during Drosophila
development
07.04 Jerry Shay University of Texas, USA Role of telomeres and telomerase in normal
and cancer cells
08.04 Rainer Hedrich Inst. for Molecular Plant Physiology and Biophysics, Guard cell action is controlled by signalling
Univ. of Wuerzburg, Biocenter, Germany
and phosphatases
11.04 Claude Antony European Molecular Biology Laboratory Electron tomography approach to study
microtubule arrays and SPBs in fission yeast cells
13.04 Michael D. Ehlers Chief Scientific Officer, Neuroscience Pfizer Global Circuit integration and subcellular trafficking
Research & Development, PharmaTherapeutics in neuronal plasticity
Neuroscience Research Unit
18.04 Frances Schweisguth Institute Pasteur, Paris Control of cell fate by Notch: a live imaging analysis
19.04 Miguel Soares IGC, Portugal Tissue Damage Control:
A central component in the establishment
of host tolerance to infection
21.04 Pedro Beltrão University of California San Francisco, USA Evolution of cellular networks: from interactions
to phenotypes
26.04 Mónica Dias IGC, Portugal Building it up and tearing it down:
centriole assembly & function in development
and evolution
27.04 Clara Reis IGC, Portugal (Post-doc seminar) MRN tethers dysfunctional telomeres for NHEJ
repair
27.04 Rasmus Larsen IGC, Portugal (Post-doc seminar) Not supplied
27.04 Takashi Koyama IGC, Portugal (Post-doc seminar) Exploring the role for FoxO in body size regulation
by the integration of insulin and ecdysone
signalling
27.04 Elsa Seixas IGC, Portugal (Post-doc seminar) Involvement of Rab GTPases in phagocytosis
27.04 Silvia Castro IGC, Portugal (Post-doc seminar) IGC in the news
29.04 Carel van Schaik Zurich University, Switzerland Cooperative breeding and the evolution
of human uniqueness
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
140

MAY 2011
DATE SPEAKER AFFILIATION TITLE
03.05 Claudine Chaouiya IGC, Portugal Qualitative modelling to gain insights into
the functioning of large regulatory networks
06.05 Volker Loeschcke Aarhus University, Denmark A systems biology approach to the study
of thermal adaptation
09.05 Helen White-Cooper Cardiff University, UK Regulation of tissue specific gene expression;
a wake-up-call from fly testes
10.05 Carlos Ribeiro IGC, Portugal The neuronal basis of nutrient choices
13.05 Alexander Stark Research Institute of Molecular Pathology (IMP), Vienna High conservation of transcription factor binding
across six Drosophila species
16.05 Michael Rose Univ. of California, Irvine, USA Genomics of experimental evolution and beyond
17.05 Gabriela Gomes IGC, Portugal Heterogeneity in host-microparasite systems
18.05 Andreia Lino IGC, Portugal (Post-doc seminar) The antibody solution
18.05 Zita Santos IGC, Portugal (Post-doc seminar) The molecular mechanisms underlying
the biogenesis of a motile axoneme
18.05 Raffaella Gozzelino IGC, Portugal (Post-doc seminar) Ferritin H chain confers tolerance to Plasmodium
infection
18.05 Laura Santos IGC, Portugal Not supplied
19.05 Etienne Danchin Univ. Paul Sabatier, Toulouse, France Beyond DNA:
integrating inclusive inheritance into the theory
of evolution
20.05 Michel O. Steinmetz Paul Scherrer Institut, Villigen-PSI, Switzerland Structure-function relationship of protein networks
regulating the microtubule cytoskeleton
23.05 Reto Gassmann Ludwig Institute for Cancer Research, UK Segregating the genome in mitosis
23.05 Ana Carvalho Ludwig Institute for Cancer Research, UK Contractile ring dynamics during cytokinesis
24.05 Miguel Godinho-Ferreira IGC, Portugal Two tales from the telomere lab
24.05 Katherine Brown EMBO Journal Behind the scenes of scientific publishing
25.05 Wen-Hsiung Li University of Chicago, USA Genetic and epigenetic factors in evolution
of gene regulation
27.05 Marcos González-Gaitin University of Geneva, Switzerland Dynamic of Dpp signalling and growth control
30.05 Mariana Guerreiro IGC, Portugal How to apply to the 2011 FCT Call for individual
fellowships
31.05 Luisa Vasconcelos, IGC, Portugal Comparing brains for avoidance, indifference
and selection responses
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
141

JUNE 2011
DATE SPEAKER AFFILIATION TITLE
03.06 Margaret McFall-Ngai Univ. of Wisconsin, USA The chronic colonisation of epithelia
by bacterial symbionts: insights from the study
of model systems
07.06 Elisabetta Padovan IGC, Portugal Immunemodulation
09.06 Michael Neuberger University of Cambridge, UK Antibody diversification by AID-mediated
DNA deamination
14.06 Louise van Oudenhove, Estación Biológica de Doñana - CSIC, Seville, Spain Trade-offs and foraging activity in Mediterannean
ant communities
16.06 Emidio Capriotti Dep. of Bioengineering Stanford Univ., USA / Computational methods for molecular biology
Dep. of Mathematics and Computer Sciences,
Univ. of Balearic Islands, Spain
17.06 Herve Vaucheret Institut Jean-Pierre Bourgin, INRA Versailles, France Genetic dissection of plant RNA degradation
pathways: lessons from silent transgenes
21.06 Michael Parkhouse IGC, Portugal Host-pathogen interaction: an evolutionary
arms race
24.06 Philip Gerrish University of New Mexico, USA Forecasting evolution:
a humble beginning...maybe
28.06 Carlos Penha-Gonçalves IGC, Portugal To be a B cell in a T cell world:
integrating innate stimuli and adaptive responses
29.06 Nelson Martins IGC, Portugal (Post-doc seminar) Evolving the immune response of Drosophila
melanogaster - insights using experimental
evolution
29.06 Manuel Marques Pita IGC, Portugal (Post-doc seminar) Objects to think with: (bio) complexity
29.06 Danesh Tarapore IGC, Portugal (Post-doc seminar) Modelling collective systems: from cells to robots
29.06 Ana Cunha IGC, Portugal Possible role of Ferritin heavy chain in Experimental
Autoimmune Encephalomyelitis
(a mouse model of multiple sclerosis)
30.06 Maria João Amorim University of Cambridge, UK Mechanisms for trafficking of Influenza
A virus Vrnas to the apical plasma membrane
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
142

JULY 2011
DATE SPEAKER AFFILIATION TITLE
01.07 Salvatore Spicuglia Centre d’Immunologie Marseille-Luminy Marseille, Control of tissue-specific gene expression
France
in normal and leukemic T cells
05.07 Thiago Carvalho IGC, Portugal Graduate education at the IGC
06.07 Marta Cascante Univ. de Barcelona, Spain Metabolism as target for novel therapies
in multifactorial diseases
08.07 Claudio Alonso University of Sussex, UK The role of RNA processing in the modulation
of Hox gene specificity during development
11.07 Graça Raposo Institut Curie, Paris Exosomes and melanosomes: the endocytic
pathway for exocytic functions
12.07 Marta Moita IGC, Portugal The sounds of silence
12.07 Susana Lima IGC, Portugal Mate choice in mice
15.07 Miguel Prudêncio IMM, Portugal Plasmodium infection:
parasite molecules, host factors and anti-malarial
interventions
18.07 Susana Seixas IPATIMUP, Porto, Portugal Examples of human adaptation in the proteolysis
universe
19.07 Carlos Tadokoro IGC, Portugal Immunethology
21.07 Susana Coelho Station Biologique de Roscoff, France The private life of Ectocarpus:
genetics and genomics of sex and alternation
of generations in a model brown alga
22.07 Gaspar Jekely Max Planck Institute, Tubingen, Germany Sensory-motor regulation of ciliary swimming
in marine zooplankton
26.07 Johan Bollen Indiana University, Bloomington, USA Scientific impact indicators and stock market
prediction models from large-scale online
attention data
28.07 Guillaume Besnard CNRS, Evolution et Diversité Biologique Lab, Toulouse Phylogenetics of multiple evolution
of the C4 photosynthetic syndrome
29.07 Tom Little University of Edinburgh, UK Host parasite coevolution and the invertebrate
immune response
AUGUST 2011
DATE SPEAKER AFFILIATION TITLE
01.08 Magda Atilano ITQB, Portugal Modifications of the cell surface allow bacteria
to evade the host immune system
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
143

SEPTEMBER 2011
DATE SPEAKER AFFILIATION TITLE
02.09 Nicola Clayton University of Cambridge, UK The evolution of shopping lists
06.09 Joaquim Léon IGC, Portugal Control of Apical Ectodermal Ridge growth
during limb development
06.09 Joana Rosario NIH-NIAID, USA NIH Grantsmanship Workshop
09.09 Miguel Martins, Cell Death Regulation Laboratory, Mitochondrial protein misfolding
MRC Toxicology Unit, Leicester, UK
and Parkinson’s disease
13.09 Florence Janody, IGC, Portugal Cancer research:
it’s not what you think. Find out more
14.09 Ioannis Theologidis IGC, Gulbenkian (Post-doc seminar) Not supplied
14.09 Catarina Henriques IGC, Portugal (Post-doc seminar) Do telomeres regulate whole organism ageing?
Characterising the telomerase mutant zebrafish.
14.09 Sheila Vidal IGC, Portugal & IMM, Portugal Information session on ERC Starting Grants 5th Call
& Margarida Trindade
16.06 Bernardo Reina-San Martin Institut de Genetique et de Biologie Moléculaire Molecular mechanism driving immunoglobulin class
et Cellulaire (IGBMC), France
switch recombination
19.09 Saumya Samarawe School of Molecular & Biomedical Science, The investigation of the role of RNA in dominant
University of Adelaide, Australia
expanded repeat diseases
20.09 Scott ONeill Faculty of Science, Monash University, Extending our understanding of Drosophila
Clayton, Australia
symbionts to develop new approaches to control
Dengue fever in human populations
20.09 William Cresko University of Oregon, USA Examining evolution genome-wide
in the threespine stickleback fish
22.09 Lounes Chikhi IGC, Portugal You're spatial to me: some consequences of space
(and time) on the population genetics
of endangered species
27.09 Rui Costa IGC, Portugal Learning new tricks
28.09 Reeta Sharma IGC, Portugal (Post-doc seminar) Shit of an elephant: What is it worth?
28.09 Post-doc Committee IGC, Portugal The Scientist Best Places Survey Results
29.09 Melanie Tanguy Inst. de Biologie Moléculaire et cellulaire du CNRS, Regulating the regulators - cellular miRNA
Univ. de Strasbourg, France
destabilisation in virus infection
30.09 Brian Tsou Sloan Kettering Institute, USA The maintenance of the centriole-cilium complex
in animals
30.09 Michael Mendes Kaltschmidt Lab Developmental Biology Program Presynaptic mGluR1 mediates synaptic plasticity
Sloan-Kettering Institute, New York
in an inhibitory circuit of the mouse spinal cord
IGC ANNUAL REPORT ‘11
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144

OCTOBER 2011
DATE SPEAKER AFFILIATION TITLE
04.10 Isabel Gordo IGC, Portugal Evolution of E. coli in the tube and in the Gut
06.10 Patrick Varga-Weisz Babraham Institute, UK Chromatin remodelling in replication
and epigenomic stability
07.10 Ryoko Kuriyama University of Minnesota, USA Centrioles in ciliogenesis and cell transformation
07.10 Pietro Corsi Oxford University, UK Yesterday as today: the many voices of evolution
11.10 Jorge Carneiro IGC, Portugal A wondrous voyage in the cockpit of a cell
12.10 Beatriz Fernandez IGC, Portugal (Post-doc seminar) The actin cytoskeleton has a crucial role
to restrain signalling pathways that control tissue
growth
12.10 Susana Gouveia IGC, Portugal Centriole elongation
13.10 Margarida Matos Faculdade de Ciências da Universidade From Nature to Lab: all hell breaks loose 18 years
de Lisboa, Portugal
studying evolutionary domestication
in Drosophila subobscura
14.10 Reuben Harris University of Minnesota, USA HIV Vif hijacks multiple cellular proteins
to counteract APOBEC3G and promote
pathogenesis
17.10 Rob Wolthuis Netherlands Cancer Institute, The Netherlands Protein destruction and synthesis in the mitotic
spindle checkpoint
18.10 Henrique Teotónio IGC, Portugal Natural selection in C. elegans experimental
populations
18.10 Andrew Holland Ludwig Institute, UK One becomes two: dividing the genome
19.10 Niels Gehring University of Cologne, Germany Gene regulation by RNA-binding protein complexes
21.10 Genevieve Almouzni Institut Curie Paris, France (hetero)chromatin assembly and nuclear
organisation
24.10 Clare Waterman Storer NIH, USA Integrating actin dynamics and adhesion
in cell migration
25.10 Edgar Gomes Paris VII, France Mechanisms of nuclear positioning during skeletal
muscle formation
25.10 Karina Xavier IGC, Portugal Integration of environmental cues with quorum
sensing
26.10 Tim Miller Washington University, USA Gene down regulation as a therapy
for neurodegenerative disease
27.10 Helder Maiato IBMC, Portugal How to make a precise chromosome segregation
machine
28.10 Fanny Gergely University of Cambridge, UK From brain development to immune response:
the many faces of the vertebrate centrosome
28.10 Kevin Foster Oxford University, UK The sociobiology of molecular systems
31.10 Bruno Houdry IBDM, Parc Scientifique de Luminy, Marseille, France Deciphering novel facets of Hox regulatory
functions during development and evolution
IGC ANNUAL REPORT ‘11
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145

NOVEMBER 2011
DATE SPEAKER AFFILIATION TITLE
03.11 James Sharpe CRG Barcelona, Spain Computer modelling of mouse limb development
reveals the need for directional cell activities
08.11 Lars Jansen IGC, Portugal On the inheritance of proteins
09.11 Ana Augusto IGC, Portugal SnRK1-induced downregulation of PPRZ
is mediated by miRNAs
10.11 Hidde Ploegh Ploegh Laboratory, Whitehead Inst. Roads to ruin: protein homeostasis
for Biomedical Research, Cambridge, USA
and its relevance for host-pathogen interactions
11.11 Santiago Zelenay Cancer Research UK, UK Immunity after death
14.11 Claudia Almeida Laboratory of Morphogenesis and Intracellular How does intracellular trafficking contribute
Signalling, CNRS UMR144, Institute Curie
to neuronal (dys)function?
15.11 Filipa Alves IGC, Portugal Biophysics and genetics of morphogenesis
17.11 Miodrag Grbic The University of Western Ontario, Canada The genome of Tetranychus urticae reveals
herbivorous pest adaptations
18.11 Jess Aguirre Dep. de Biología Celular y Desarrollo, Inst. Ros, stress signal transduction and cell
de Fisiología Celular, Univ. Nacional Autónoma differentiation in filamentous fungi
de México, Mexico
21.11 Thaddeus George Director of Biology, Amnis Discriminating cells based on their appearance
using ImageStream cytometry
22.11 João Garcia IGC, Portugal High-performance computational servers
and other computational matters
22.11 José Leal IGC, Portugal The Bioinformatics Unit
23.11 Carla Lopes IGC, Portugal (Post-doc seminar) Centrosome abnormalities in cancer progression
23.11 Kai Konrad IGC, Portugal (Post-doc seminar) The role of ion channels in membrane potential
polarity control during pollen tube growth
25.11 Michael Turelli University of California Davis, USA Wolbachia Evolution
29.11 Lucas Sanchez Centro de Investigaciones Biológicas (C.S.I.C.), Spain Evolutionary paths for sex-determining
mechanisms based on X-chromosome elimination:
The sciarid system
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
146

DECEMBER 2011
DATE SPEAKER AFFILIATION TITLE
02.02 Johannes Jaeger EMBL/CRG Research Unit in Systems Biology, Shift happens:
CRG-Centre de Regulació Genòmica, Spain
the evolutionary and developmental dynamics
of the gap gene network
06.02 Vasco Barreto IGC, Portugal Physiologic DNA double strand breaks
in B lymphocytes and beyond
06.02 Mónica Roxo Rosa Faculdade de Engenharia, Universidade Católica A contribution to get insight into the virulence
Portuguesa, Campus de Sintra
of the human gastric pathogen Helicobacter pylori
07.12 Francisco Pereira IGC, Portugal (Post-doc seminar) Not supplied
07. 12 Susana Ramos IGC, Portugal (Post-doc seminar) Not supplied
09.12 Christen Mirth IGC, Portugal The Eco-Devo of body size: elucidating
the mechanisms that determine body size
and proportions in response to nutrition
in fruit flies
09.02 David Pellman Danna Farber and Harvard Medical School, USA Genome evolution driven by centrosome
amplification
13.12 Ana Mena IGC, Portugal A tour of the animal house facility guidelines
14.12 Catarina Carmo IGC, Portugal (Post-doc seminar) Identification of Wolbachia effector proteins
14.12 Pedro Coelho IGC, Portugal (Post-doc seminar) The evolution of host-parasite interactions
at the cellular level
15.12 Marta Vicente-Crespo IGC, Portugal Nonsense-mediated mRNA Decay in vivo:
keeping down the nonsense
16.12 António Jacinto CEDOC, Portugal CEDOC
19.12 Geert Kops University of Utrecht, The Netherlands Coupling the microtubule attachment site
on kinetochores to mitotic checkpoint signalling
20.12 Joana Sá IGC, Portugal Experimenting with politics and risk perception
22.12 David J. Solecki St. Jude Children's Research Hospital, Memphis, USA Siah regulation of Pard3A controls neuronal cell
adhesion during germinal zone exit
IGC ANNUAL REPORT ‘11
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147

PRESENTATIONS BY IGC RESEARCHERS
AT INTERNATIONAL MEETINGS
FILIPA ALVES
Biophysical models for ion dynamics in cell polarisation and apical growth
The 8th International Symposium on Networks in Bioinformatics (ISNB 2011)
Amsterdam, The Netherlands
April 2011
Modeling the development and evolution of pigmentation patterns in butterflies
Geometry of Interfaces
Primošten, Croatia
October 2011
JOÃO ALVES
The evolutionary history of an inversion polymorphism in the human genome
European Meeting of PhD Students in Evolutionary Biology (EMPSEB)
Seia, Portugal
August 2011
ALEKOS ATHANASIADIS
Conformational junctions in DNA and genomic instability
XXIII international congress of Crystallography
Madrid, Spain
August 2011
ELENA BAENA-GONZÁLEZ
Early signalling in the stress response
Invited speaker, 6th International PhD Summer School on Environmental Signalling
Utrecht University, The Netherlands
August 2011
Dissecting the SnRK1 signalling pathway
Invited speaker, 1st European meeting on the “TOR kinase signalling pathway in plants”
INRA-Versailles, France
December 2011
VÍTOR BARBOSA
Meiotic surveillance of the cohesion protein dPds5 in insulator body formation
requires ATM but not ATR
52nd Drosophila Research Conference, Genetics Society of America, USA
March 2011
JÖRG BECKER
Transcriptomics approaches to study the Arabidopsis male germline
and Medicago symbioses
OCAST meeting, Ardmore, Oklahoma, USA
August 2011
PATRÍCIA BELDADE
Evo-devo and the mechanisms of morphological diversification
Seminar at the Institute for Evolution and Biodiversity of Munster University
Münster, Germany
April 2011
The origin and diversification of novel traits
Discussion group "The future of Evo-Devo", Foundation des Treilles, Les Treilles
Tourtour, France
April 2011
The origin and diversification of novel traits:
a locus affecting embryonic development and contributing to wing pattern variation
Institute of Biology, Leiden University, the Netherlands
June 2011
IGC ANNUAL REPORT ‘11
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148

On the origin and diversification of novel traits: old genes, new tricks
13th Congress of the European Society for Evolutionary Biology
Tuebingen, Germany
August 2011
MÓNICA BETTENCOURT DIAS
CABD
Seville, Spain
January 2011
Intitut de Genetique Humaine
Montpellier, France
February 2011
ETH
Zurique, Switzerland
March 2011
University of Geneva, Switzerland
March 2011
Annual Helsinki Biomedical Graduate School (HBGS) Student Council Symposium
on “Cell cycle"
Nordic Cilia Meeting, Denmark
March 2011
??????and Proliferation”
Helsinki, Finland.
April 2011
LMCB
London, UK
June 2011
FEBS/DGZ workshop in Potsdam
"The spider's web: how microtubules organise cellular space"
June 2011
Clare Hall (CRUK Institute) London, UK
July 2011
GRC Motile & Contractile Systems, Colby-Sawyer College in New London
New Hampshire, USA
August 2011
European Drosophila Research Conference
Lisbon
September 2011
Centrosome and SPB Conference
Barcelona
October 2011
IRB PhD student Symposia
Barcelona
November 2011
Genes and Cancer Meeting
Warwick, UK
December 2011
LEONOR BOAVIDA
Potential functions for gamete-expressed tetraspanins in sexual plant reproduction
XXXVI Jornadas Portuguesas de Genética
Coimbra, Portugal
May 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
149

Tetraspanins in higher plants: a functional role in sexual reproduction
FASEB Summer Conferences: Membrane Organization by Molecular Scaffolds,
Saxtons River, Vermont, USA
July 2011
SOFIA BRAGA
The heterogeneity of breast cancer
Canceromatics II, Multilevel Interpretation of Cancer genome, Centro Nacional
de Investigaciones Oncologicas
Madrid, Spain
March 2011
Centrosome components and regulators as clinically relevant prognostic markers
in cancer
15th Annual Meeting Sociedade Portuguesa Genética Humana
Lisbon, Portugal
November 2011
JOANA CARDOSO
Translational Bioinformatics at the Computational Genomics Laboratory
VII Conferência Estatística e Qualidade em Saúde
Lisbon, Portugal
May 2011
CLAUDINE CHAOUIYA
Logical models provide insights into regulatory networks dynamics
Invited seminar, CADP
Seville, Spain
March 2011
Current developments in qualitative modelling of biological networks
COMBINE (Computational Modelling in Biology Network)
Heidelberg, Germany
September 2011
LOUNES CHIKHI
Génétique des populations dans l’espace et dans le temps:
reconstruire l’histoire démographique des populations
Biodiversité et Informatique
Grenoble, Switzerland
June 2011
Population genetics in space and time: can we reconstruct the demographic
history of (endangered) populations
European Meeting of PhD Students in Evolutionary Biology (EMPSEB)
Seia, Portugal
August 2011
Population genetics in space and time: can we reconstruct the demographic
history of (endangered) populations?
ISPA
Lisbon, Portugal
September 2011
Very spatial indeed: some consequences of space (and time) on the population
genetics of endangered species
TiBE, CIBIO
Vairão, Portugal
December 2011
Conservation, phylogéographie et génétique de lémuriens dans des habitats
fragmentés de Madagascar et de l’archipel des Comores
Fondation Recherche et Biodiversité
Paris, France
December 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
150

HELENA COSTA
Mechanism of IL-8 induction by HCMV UL76
9th Joint Meeting of the International Cytokine Society (ICS)
and the International Society for Interferon and Cytokine Research (ISICR)
Florence, Italy
October 2011
NUNO COSTA
Active regulatory T-cells contribute to broadened T-cell repertoire diversity
in ivIg-treated SLE patients
2º Congresso Nacional de Auto-Imunidade, Almancil, Portugal
April 2011
RUI COSTA
First Songbird Satellite Symposium
Washington, USA
CRG
Barcelona, Spain
Janelia Conference ‘The Neural Basis of Motor Control’
Ashburn, USA
CRG
Barcelona, Spain
Riken BSI
Barcelona, Wako, Japan
Development of Brain and Mind Symposium
Kobe, Japan
Keynote, Portuguese Society for Educational Sciences
Guarda, Portugal
ISPA
Lisbon, Portugal
IMP
Vienna, Austria
100th Anniversary University of Lisbon
Portugal
College de France
Paris, France
CSHL
Cold Spring Harbor, USA
103rd Titisee Conference
Titisee, Germany
Janelia Farm Research Campus
Ashburn, USA
FMI
Basel, Switzerland
JOCELYNE DEMENGEOT
From clinical trials to SLE pathogenesis and vice versa:
Did we explore everything we could from animal models?
8th European Lupus Meeting 2008
Porto, Portugal
April 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
151

YOAN DIEKMANN
10000 Rabs for the cell biologist
EMBO Conference on Comparative Genomics of Eukaryotic Microorganisms
San Feliu de Guixols, Spain
October 2011
PAULA DUQUE
The plant-specific SR45 splicing factor is a novel player
in hexokinase-independent glucose signalling in Arabidopsis
Second International EURASNET Conference on Alternative Splicing
Granada, Spain
March 2011
The plant-specific SR45 splicing factor is a novel player
in hexokinase-independent glucose signalling in Arabidopsis
Second International EURASNET Conference on Alternative Splicing
Granada, Spain
March 2011
Alternative splicing and proteomic diversity in plant responses
to environmental stress
Universidade do Algarve, Faro, Portugal
July 2011
Alternative splicing and proteomic diversity in plant responses
to environmental stress
Universidade do Algarve
Faro, Portugal
July 2011
JOSÉ FEIJÓ
Signalling with ions: merging genetics with biophysics on the pollen tube system
Dept Cell and Molecular Biology
University of Maryland
USA
Space and time coordination of cellular growth processes by free cytosolic ions
in pollen tubes
Plenary Speaker, Wagenigen, 2011, “Botanical Microscopy Meeting”
Royal Microscopical Society
Wagenigen, The Netherlands
Space and time coordination of cellular growth processes by free cytosolic ions
in pollen tubes
Estación Experimental Zaidin, Granada
and University of Granada, Spain
April 2011
Space and time coordination of cellular growth processes by free cytosolic ions
in pollen tubes
Plenary Speaker, Biophysical Basis of Development EMBO workshop
IGC
Oeiras, Portugal
May 2011
Of models and mechanisms of ion dynamics and signalling in pollen tubes
MPI, Cologne University
Germany
June 2011
Space and time coordination of cellular growth processes by free cytosolic ions
in pollen tubes
Keynote speaker, Society for Experimental Biology
Glasgow, UK
July 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
152

Of models and mechanisms of ion dynamics and signalling in pollen tubes
Symposium Keynote speaker, International Botany Meeting
Melbourne, Australia
July 2011
Space and time coordination of cellular growth processes by free cytosolic ions
in pollen tubes
The Harold Woolhouse Lecture 2011
University of Adelaide, Australia
August 2011
Of models and mechanisms of ion dynamics and signalling in pollen tubes
RCN pollen workshop, Satellite meeting to the ASPB
Minnesota, USA
August 2011
Excitement in sexual plant reproduction: the remarkable biology of pollen tubes
Genetics Society
Coimbra, Portugal
PEDRO FERNANDES
Treino em Bioinformática - o programa GTPB
VII Conferência Estatística e Qualidade na Saúde, IHMT-UNL, Lisbon, Portugal
May 2011
Skills in Bioinformatics via training courses
Interbio International Meeting, Valencia, Spain
Nov 2011
CONSTANTIN FESEL
T-cell regulation in SLE patients and unaffected relatives
8th European Lupus Meeting, Porto, Portugal
April 2011
MIGUEL GODINHO FERREIRA
MRN self-dimerisation, not its checkpoint function, is required for NHEJ
at fission yeast telomeres
Telomeres and Telomerase Meeting, CSHL
NY, USA
May 2011
Establishing anti-telomerase therapy for melanoma in zebrafish
IPATIMUP
Porto, Portugal
June 2011
Zebrafish telomerase mutant - a model system for ageing and cancer
CECAD - Cluster of Excellence in Aging-associated Diseases
Cologne, Germany.
June 2011
Chromosome Structure is an Evolutionary Selectable Trait
The Sixth International Fission Yeast Meeting, Boston, USA
June 2011
Telomeres and chromosome-end protection
Institute of Biochemistry
ETH Zürich, Switzerland
September 2011
GABRIELA GOMES
Measures of immunity across scales
Infection Dynamics: Bridging the Gap between Theory and Application
Utrecht Centre for Infection Dynamics
The Netherlands
March 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
153

Heterogeneity in host-microparasite systems
Phylodynamics, NESCent - National Evolutionary Synthesis Centre
Durham, USA
May 2011
Heterogeneity in antibody range and the antigenic drift of influenza A viruses
VIII European Conference on Mathematical and Theoretical Biology
Krakow, Poland.
June 2011
Heterogeneity in antibody range and the antigenic drift of influenza viruses
From Chaos to Complexity, Mathematics Interdisciplinary Research
University of Warwick, UK
July 2011
RICARDO GONÇALVES
Metabolism and nutritional decision, present and future of a model
Instituto Superior de Saúde do Alto Ave (ISAVE), Póvoa de Lanhoso, Portugal
November 2011
MARC GOUW
mtocDB: the Evolution of Microtuble derived organelles, RSGTP
Lisbon, Portugal
May 2011
INBAL ISRAELY
The dendritic branch as an integrative unit for protein synthesis dependent
synaptic plasticity
Synapse: From Molecules to Circuits & Behaviour
Cold Spring Harbor Laboratory Meeting, CSHL
USA
April 2011
FLORENCE JANODY
The actin cytoskeleton: A tumour suppressor organelle
Skirball Institute
New York, USA
April 2011
The role of the actin cytoskeleton in mechano-transduction and tissue growth
Biophysical Mechanisms of Development EMBO Workshop
IGC
Oeiras, Portugal
May 2011
LARS JANSEN
The centromere: A showcase for epigenetic inheritance
Instituto de Biologia Molecular e Celular (IBMC)
Porto, Portugal
February 2011
The centromere: A showcase for epigenetic inheritance
Centro de Biomedicina Molecular e Estrutural, Faro, Portugal
March 2011
The centromere: A showcase for epigenetic inheritance
Young Investigator Programme meeting, EMBL
Heidelberg, Germany
May 2011
Epigenetics and the Rebirth of Lamarckism
SIMC symposium
Museu da Ciência
Coimbra, Portugal
May 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
154

The centromere: A showcase for epigenetic inheritance
Institute for Genetics
University of Cologne
Cologne, Germany
June 2011
Centromere inheritance and propagation
2nd Dynamic kinetochore workshop, IMP
Vienna, Austria
June 2011
The centromere: A showcase for epigenetic inheritance
ETH
Zurich, Switzerland
November 2011
Locus specific histone turnover and assembly
YIP Chromatin network meeting, EMBL
Heidelberg, Germany
December 2011
MARIA ADELINA JERÓNIMO
The origin of novel traits: epidermal wounds and butterfly eyespots
17th EMPSEB (European Meeting of PhD students in Evolutionary Biology)
Seia, Portugal
August 2011
CATARINA JÚLIO
Should scientific research institutions communicate directly with public?
I National Meeting of Evolutionary Biology, Science communication workshop,
Museu da Ciência da Universidade de Coimbra
Portugal
December 2011
ROBERTO KELLER
Ants protect their mouthparts by locking them in place
Congrès 2011 de la section française de l'UIEIS
Banyuls, France
April 2011
Queen, workers and working queens: morphological adaptations related
to caste-specific behaviours in ants
Department of Zoology
University of Cambridge, UK
November 2011
TAKASHI KOYAMA
Exploring the role for FoxO in body size regulation by the integration of insulin
and ecdysone signalling
Ecdysone Workshop at the 52nd Annual Drosophila Research Conference,
San Diego, U.S.A.
March 2011
BEATRIZ LUNA
Relating Formalisms for the Qualitative Modelling of Regulatory Networks
5th International Conference on Practical Applications of Computational
Biology & Bioinformatics (PACBB 2011)
Salamanca, Spain
April 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
155

ZACHARY MAINEN
Task-dependent strategies for decision-making under uncertainty
Columbia University
New York, USA
April 2011
Neural circuits for odor-guided decisions in the rat
Société des Neurosciences 10e Colloque
Marseille, France
May 2011
Targeting the serotonin system using optogenetics:
Towards a post-pharmacological view
Causal Neuroscience, FENS-IBRO-SfN School
Bertinoro, Italy
June 2011
Knowing what you know: Models and mechanisms for judgments of confidence
What Makes Us Human? 2011 GABBA Annual Symposium
Porto, Portugal
July 2011
Neural mechanisms for decision making in the rat:
Uncertainty in brain and behavior
Genes, circuits, behaviour Symposium
RIKEN Brain Science Institute,
Tokyo, Japan
October 2011
MOISÉS MALLO
Making animals with the right number of ribs: who has the instruction manual?
Instituto Superior de Agronomia
Lisbon, Portugal
June 2011
What makes Hox10 proteins fail to repress rib formation
2011 COST Meeting on Hox and Tale Transcription Factors in Development
and Disease
Carry-le-Rouet, France
October 2011
ANA RITA MATEUS
Hormonal manipulations and developmental plasticity
17th EMPSEB (European Meeting of PhD students in Evolutionary Biology)
Seia, Portugal
August 2011
Hormonal manipulations and developmental plasticity: independence of highly
integrated traits
VII Encontro Nacional de Biologia Evolutiva
Museu de Ciência da Universidade de Coimbra
Coimbra, Portugal
December 2011
CHRISTEN MIRTH
How nutrition regulates adult body size: lessons from fruit flies
CIC bioGUNE
Derio, Spain
March 2011
The evolution of foraging behaviour in larvae of the genus Drosophila
Centro de Regulació Genômica
Barcelona, Spain
June 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
156

Mechanisms determining adult body size and proportions in response to nutrition
in Drosophila melanogaster
Centro Andaluz de Biología del Desarrollo (CABD)
Seville, Spain.
July 2011
Ecdysone regulates size-dependent development
Endocrine control of growth, body size and allometric scaling symposium
at the North American Society for Comparative Endocrinology Meeting
Ann Arbor, USA.
July 2011
The Development and Evolution of Environmentally-Dependent Traits
Junior European Drosophila Investigators Meeting
Leysin, Switzerland.
September 2011
MARTA MOITA
Producing and Perceiving Complex Acoustic Signals:
Songbirds and Mice as Model Systems Conference
Janelia Farm, USA
March 2011
103rd International Titisee Conference on “Genetic analysis of neural circuits”
Titisee, Germany
March 2011
Cutting edge in synapse research
NAIST, Japan
December 2011
RIKEN Brain Science Institute
Japan
December 2011
PEDRO MONTEIRO
Modélisation et vérification formelle des réseaux de régulation biologique :
vers une approche intégrée
Workshop Formalisme logique, apports et défis pour la modélisation de réseaux
de régulation biologique
Rabat, Morocco
April 2011
RICARDO PAIVA
T cell Maturation Stage Conditions de novo Foxp3 Expression in vivo
Yale School of Medicine, Department of Immunobiology
New Haven, Connecticut, USA
January 2011
MICHAEL PARKHOUSE
Manipulation of interferon responses by African Swine Fever Virus
AFRISK
Seville, Spain
January 2011
The diversity of immune responses to microbes
8th European Lupus Meeting
Porto, Portugal
April 2011
Strategies for the control of T. solium cysticercosis
CYTED
UNAM, México
May 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
157

African Swine Fever Virus has evolved multiple strategies to manipulate
the interferon responses by the host
AFRISK
Lisbon, Portugal
September 2011
El control de la cisticercosis bovina, porcina y humana
XX Congresso Latinoamericano de Parasitologia
Bogota, Colombia
September 2011
Control de cisticercosis por vacunacion
Cisticercosis bovina: desafio a ser vencido Workshop
UNESP
Brazil
November 2011
Estratégias racionales para el desarrollo de vacunas
Instituto Biomed
Venezuela
December 2011
BÁRBARA PARREIRA
The impact of the social structure on patterns of genetic diversity:
a simulation approach
17th European Meeting of PhD Students in Evolutionary Biology (EMPSEB)
Seia, Portugal
August 2011
The impact of the social structure on patterns of genetic diversity:
a simulation approach
TiBE, CIBIO
Vairão, Portugal
December 2011
JOE PATON
A representation of time for learning in the striatum of behaving rats
Paris, France
A representation of time for reinforcement learning in the striatum of behaving rats
Parallel distributed processing
Princeton, NJ, USA
A representation of time for learning in the striatum of behaving rats
Decision making in neural circuits
Ashburn, VA, USA
A representation of time for learning in the striatum of behaving rats
Group meeting of Ann Graybeil lab, MIT
Boston, USA
JOSÉ PEREIRA-LEAL
New bioinformatics tools for an evolutionary cell biology
Utrecht, Netherlands
March 2011
New bioinformatics tools for an evolutionary cell biology
EMBnet meeting
Oeiras, Portugal
April 2011
mtodDB
Madrid, Spain
April 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
158

The evolutionary dynamics of (Rab) proteins and interactions
Interbio Meeting
Oeiras, Portugal
May 2011
The computational Genomics Laboratory
3E
Caparica, Portugal
June 2011
Towards an evolutionary cell biology and its translational applications
Computational Methods in Functional Genomics
Bertinoro, Italy
September 2011
The evolution of cellular structures and compartments
Dusseldorf, Germany
November 2011
The evolution of intracellular compartments and its translational applications
Viena, Austria
December 2011
CARLOS RIBEIRO
The Molecular and Neuronal Control of Nutrient Choice in Drosophila
ICVS, University of Minho, Braga, Portugal
April 2011
The Molecular and Neuronal Control of Nutrient Choice in Drosophila
XII Meeting of the Portuguese Society for Neuroscience
Lisbon, Portugal
May 2011
The Molecular and Neuronal Control of Nutrient Choice in Drosophila
Instituto de Medicina Molecular
University of Lisbon
Lisbon, Portugal
June 2011
Where did I go and how did I get there?
E3 forum, Education, Employment, Entrpreneurship
MIT Portugal Program
Lisbon
June 2011
The Behavior and metabolism laboratory
The first Junior European Drosophila Investigator meeting
Leysin, Switzerland
September 2011
The Molecular and Neuronal Control of Nutrient Choice in Drosophila
22nd European Drosophila Research Conference
Lisbon, Portugal
September 2011
The Molecular and Neuronal Control of Nutrient Choice in Drosophila
Deprtment of Zoology
University of Cambridge
Cambridge, UK
December 2011
LUIS M. ROCHA
The complex systems approach to modelling biochemical regulation
and organisation
Colloquium, IGC
Portugal
February 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
159

Schema Redescription in Automata Networks: Revisiting Emergence
in Complex Systems
Cognitive Science Programme
Indiana University
Bloomington, IN, USA
March 2011
Text Classification of the Biomedical Literature
Networks and Complex Systems Talk Series
Indian University
Bloomington, IN, USA
March 2011
Collective Computation in Biochemical Networks: Canalization,
Control and Modularity
University of Nebraska at Lincoln, USA
October 2011
Reality is stranger than fiction: Exploring the Evolutionary Role of RNA Editing
with Computational Models
Colloquium Speaker, Theoretical Biology Seminar Series
CREA-CNRS
Paris, France
November 2011
JORDI SALMONA
Signature of a pre-human population collapse in the critically endangered
Reunion Island endemic forest bird Coracina newtoni
TiBE, CIBIO
Vairão, Portugal
December 2011
RAQUEL SANTOS
The oocyte-specific function of dPds5 in insulator assembly is monitored by the
checkpoint kinase ATM but not by ATR
22nd European Drosophila Research Conference
September 2011
REETA SHARMA
Addressing the genetic response of Bornean elephants to habitat loss
and fragmentation
ESEB
Tübingen, Germany
August 2011
LEILA SHIRAI
Evo-devo in Bicyclus anynana
Embryo Club, Joint Meeting of Lisbon-based research groups
in Developmental Biology
Calouste Gulbenkian Foundaiton
Portugal
March 2011
CARLOS E. TADOKORO
Immunethology
Faculdade de Ciências, Universidade de Lisboa
Portugal
January 2011
Immunethology
Otto-von-Guerricke University
Magdeburg, Germany
March 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
160

HENRIQUE TEÓTONIO
The genetic basis of adaptation in C. Elegans
Instituto de Medicina Molecular
Lisbon, Portugal
March 2011
The genetic basis of adaptation in C. Elegans
University of Nice
Nice, France
March 2011
The genetic basis of adaptation in C. Elegans
Portugalia Genetica, Porto Portugal
April 2011
The genetic basis of adaptation in C. Elegans
University of Vienna, Vienna Austria
May 2011
The genetic basis of adaptation in C. Elegans
Worm Meeting
Los Angeles USA
June 2011
The genetic basis of adaptation in C. Elegans
European Evolutionary Biology
Tubingen, Germany
August 2011
The genetic basis of adaptation in C. Elegans
Universidade de Lisboa
Lisbon, Portugal
The genetic basis of adaptation in C. Elegans
University of Aarhus
Aarhus, Denmark
November 2011
The genetic basis of adaptation in C. Elegans
Selection in Populations
Paris, France
December 2011
MARIA LUÍSA VASCONCELOS
Search for neuronal circuits of innate responses in the fruit fly
National Institute of Medical Research (NIMR)
London, UK
October 2011
SHEILA VIDAL
Financiamento em Ciência: Elaboração de um Projecto de Investigação
1º Encontro dos Bolseiros de Doutoramento Gulbenkian de Países Africanos de
Língua Oficial Portuguesa nas áreas das Doenças Tropicais Negligenciadas e das
Ciências da Saúde, Fundação Calouste Gulbenkian, Lisbon, Portugal
May 2011
Importance of Mobility within RM&A Professional Development Training:
European & International Internship Programmes
Annual Conference EARMA 2012, Agricultural School, Instituto Politécnico de
Bragança, Portugal
June 2011
IGC ANNUAL REPORT ‘11
SEMINARS, WORKSHOPS, AND MEETINGS
161

CONFERENCES, MEETINGS,
WORKSHOPS, SUMMER SCHOOLS
ITQB-IGC PLANT INTERACTION MEETINGS
Organisers: Nelson Saibo (ITQB) and Elena Baena-González (IGC)
The main purpose of these monthly meetings is to enhance the interaction
between the plant groups of the ITQB, IBET, and IGC, to exchange ideas with
regard to practical/conceptual problems in the current projects and in the longterm
to promote collaborations amongst these institutions.
AMeeGuS
3 - 5 February 2011
Organisers: PhD Student Committee - Pedro Lima, Inês Trancoso, Ali Ozgur
Argunsah, Marisa Oliveira, Rui Castanhinha, Alex Leitão, Bruno Afonso (IGC)
Funding by: IGC, STAB Vida, Dias de Sousa, Quilaban, VWR, Biognostica (Portugal)
The primary goal of the annual PhD retreat is to create an open, inspiring
and comfortable atmosphere for all PhD students of the IGC to discuss their
research with peers and a small number of senior scientists, both from the IGC
and other international research centres.
DISTANCE AND eLEARNING TECHNOLOGIES
2 March 2011
Organisers: Pedro Fernandes (IGC)
Funding by: Self-financed by participants
An open discussion on the impact of distance and eLearning technologies on
the acquisition of skills.
INTRODUCTION TO FLOW CYTOMETRY
27 - 30 April; 29 November - 3 December 2011
Organisers: Rui Gardner (IGC)
The aim of these courses is to introduce researchers to the basic concepts of
flow cytometry and provide hands-on experience in the most important applications,
namely, immunophenotyping and cell cycle analysis.
IGC PRACTICAL COURSE ON ANIMAL HANDLING AND EXPERIMENTATION
- GOOD PRACTICES WITH RODENTS, FISH AND FROGS
3 - 6 May 2011
Organisers: Ana Mena, Manuel Rebelo and Jocelyne Demengeot (IGC)
Funding by: Ultragene, Tecniplast, Aquatic Solutions
The aim of this course was to train researchers that carry out experiments
with animals in basic procedures, following Federation of European Laboratory
Animal Science Associations (FELASA) guidelines. Training in laboratory animal
sciences is mandatory by Portuguese and European Law, in order for researchers
to be considered capable to work with animals. This 20 hours course was
structured to cover all vertebrate models in use at the IGC, namely mouse, rat,
zebrafish and frog.
DIA DA BIODIVERSIDADE / JOURNÉE DE LA BIODIVERSITÉ / BIODIVERSITY DAY
20 May 2011
Organisers: Lounes Chikhi (IGC), Jean-Pierre Courtiat (French Embassy in Lisbon)
Funding by: IGC, French Embassy in Lisbon
With the aim of reflecting on real changes that happened during the 2010 International
Year of Biodiversity, and on future prospects and priorities, this oneday
symposium (held at the Calouste Gulbenkian Foundation) provided a forum
for citizens and scientists to discuss several relevant issues in biodiversity and
species conservation, namely: the rapid decline in species number, threats to
the environment and to natural resources. Researchers working in Portugal and
in France were invited to take part.
IGC ANNUAL REPORT ‘11
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162

EMBnet - ANNUAL GENERAL MEETING 2011
22 - 25 May 2011
Organisers: Pedro Fernandes (IGC)
Funding by: EMBnet
EMBnet Mini Symposium, Meetings and AGM
BIOPHYSICAL MECHANISMS OF DEVELOPMENT
24 - 27 May 2011
Organisers: Beatriz García Fernández, Ana Catarina Certal, Ana Borges
and Filipa Alves (IGC), Ana Tavares (Universidade Técnica de Lisboa)
Funding by: EMBO, The EMBO Journal, Applicable Electronics LLC, Grupo Taper,
Zeiss, Leica, Utragene, Tecniplast, Aquatic Solutions, Delta Q,
Oeiras City Council, Sociedade Portuguesa de Biologia
do Desenvolvimento, Fundação para a Ciência e a Tecnoloiga,
Fundação Calouste Gulbenkian (Portugal)
In recent years, a combination of new imaging techniques, genetics and computational
biology have provided an integrated framework to explore biophysical
phenomena with a resolution thus far difficult to achieve. This workshop aimed
to discuss recent advances and new mechanisms arising in the field of developmental
biophysics in several model organisms, extending to developmentrelated
contexts such as tissue regeneration and tumourigenesis. The main goal
was to bring together researchers working at the frontiers of developmental
biology and physics, that employ a wide range of quantitative biology approaches.
In total, 99 people attended. The panel of 19 invited speakers and five selected
speakers were organised into five sessions: Ion dynamics in development;
Regeneration & disease; Tissue mechanics & tension in morphogenesis; Cellular
mechanosensing & mechanotransduction; Morphogen gradients & pattern formation
(see Development 138: 4111).
MASTER COURSES IN BIOINFORMATICS AND BIOLOGICAL COMPUTATION,
CELL BIOLOGY AND BIOTECHNOLOGY AND IN MOLECULAR BIOLOGY
15 - 17 June 2011
Organisers: Jörg Becker, Patricia Pereira and Filipe Borges (IGC)
Sixteen masters students of the Faculty of Sciences (University of Lisbon)
learned how to analyse microarray data and performed their own analysis in
three separate projects.
GENOME BIOLOGY AND EVOLUTION
1 - 19 August 2011
Organisers: Jose Pereira Leal and Thiago Carvalho (IGC)
Funding by: Volkswagen Foundation (Germany), Calouste Gulbenkian Foundation
(Portugal)
An international Summer School that brought together leaders in the field
(27 speakers) with approximately 40 European students.
EUROPEAN DROSOPHILA RESEARCH CONFERENCE
21 - 24 September 2011
Organisers: Vitor Barbosa, Élio Sucena and Luis Teixeira (IGC), António Jacinto
(CEDOC), Cláudio Sunkel (IBMC)
With over 500 participants from all Europe, the biannual European meeting
of Drosophila researchers took place at the Calouste Gulbenkian Foundation
and the satellite workshops were held at the IGC. In addition to a panel of
leading plenary speakers the conference included sessions on cell biology, cell
cycle, chromatin and gene expression, evo-devo, immunity, models of human
disease, neurobiology and behaviour, next generation resources, organogenesis
and morphogenesis, patterning, physiology, and signaling. The “Drosophila symbionts:
from pathogens to mutualists” workshop, organised within the European
Drosophila Research Conference, and the "Making and maintaining the fly
intestine" workshop brought together talks at the intersection of Drosophila
and immunology fields. There were about 80 participants in this workshop.
IGC ANNUAL REPORT ‘11
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PathProt-4
21 - 22 October 2011
Organisers: Pedro Fernandes (IGC), Roman Zubarev (Karolinska Institute,
Sweden), Alexander Kel (GenExplain GmbH, Germany)
Funding by: Self-financed by participants
PathProt is the international forum for Pathway Analysis in Proteomics. We are
an informal discussion forum that holds brainstorming meetings.
THEORETICAL COURSE IN LABORATORY ANIMAL SCIENCE - FELASA CATEGORY B
14 - 18 November 2011
Organisers: Ana Mena, Manuel Rebelo and Jocelyne Demengeot (IGC)
The aim of this course was to teach theoretical concepts to researchers that
carry out experiments with animals, following FELASA guidelines and in fulfillment
of Portuguese and European Law, which require training in order for
researchers be considered capable to work with animals.
ANNUAL MEETING OF THE PORTUGUESE SOCIETY OF IMMUNOLOGY
29 - 30 November 2011
Organisers: Jocelyne Demengeot, Jorge Carneiro, Thiago Carvalho
and Carlos Tadokoro (IGC)
Funding by: Sociedade Portuguesa de Imunologia, Calouste Gulbenkian
Foundation, Actimel, Roche, PeproTech (Portugal)
Entitled “Portrait of the immune system: history and perspective”, this meeting
hosted 120 participants. It shared a session with the symposium Jerne100:
a century of Niels K. Jerne, a gathering of colleagues, associates, and friends of
one of the most remarkable and intemporal figures in immunology. It provided
the opportunity to present and discuss work with members of the society and
with several speakers selected from the Jerne100 symposium.
GAMEETS 2011 - IGC NETWORKS:
INTERACTIONS WITHIN THE IGC PROGRAMMES
27 December 2011
Organisers: Miguel Godinho Ferreira, Rui Martinho (IGC) and Greta Martins (IGC)
Funding by: Oeiras City Council
The aim of this annual meeting was to present examples of past and ongoing
collaborations within Gulbenkian Alumni and discuss ways to stimulate such collaborative
research projects.
IGC ANNUAL REPORT ‘11
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164

PUBLIC
ENGAGEMENT
IN SCIENCE

SCIENCE
COMMUNICATION
AND OUTREACH
Ana Godinho Head
PhD in Developmental Neurobiology, University of London, UK, 1999
Head of service since January 2008
The IGC runs a dedicated science communication and outreach programme,
which actively engages IGC researchers and staff in its two main aims: to raise
the profile of the IGC and its research, both nationally and internationally, and
to promote public engagement in science. A further, closely linked goal, is to
provide scientists with tools to effectively communicate scientific research to
non-specialist audiences, specifically to engage the general public and the media.
Projects are built around two-way, dialogue-based interactions between
IGC researchers, students and staff with a range of audiences: the media, students,
teachers, the general public, artists and policy makers.
STAFF
Filipa Barbosa (Post-doc) (left in January)
Sílvia Castro (Post-doc) (left in August)
Inês Domingues (Post-doc)(Started in November)
Ana Mena (Post-doc)
Vitor Faustino (with Collective Dynamics Group) (Project Manager)
Catarina Júlio (Project Officer)
MAJOR PROJECTS AND ACCOMPLISHMENTS
Press Office
Research developments by IGC scientists are announced through press releases,
which are covered in national and international media. In 2011, 300
news clippings mentioning the IGC were registered, in Portuguese (80%) and
international (20%) media outlets (values are underestimations). In total, 16
press releases were sent out; on average, each press release generated 12.1
news items. The IGC has established itself as a major point of call for journalists:
in 2011, a total of 15 spontaneous media enquiries were received, not
directly related to media contacts made by the IGC. Our database of national
and international print, broadcast and online media outlets reaches over
7,000 reporters, in over 60 countries.
Science on TV - a study into science and technology in the news
The IGC and the national media regulator Entidade Reguladora para a Comunicação
Social (ERC) launched a study to quantify coverage of science
and technology in national television news programmes. The aim is to understand
how the media contribute to raising awareness of scientific research,
and, subsequently, to scientific literacy. The findings of this study shall be
published and discussed at a public meeting for scientists, decision-makers,
journalists and communication scholars.
Schools´ outreach
Personal interactions with students and teachers are an important part
of our outreach. IGC scientists and the science communication team took
hands-on activities to school science days and science fairs (D. Pedro IV
School - Queluz, Gama Barros Secondary Schoool - Cacém), holiday camps
(ACDP Basketball Holiday Camp - Oeiras), and organised informal talks by IGC
scientists in several cities (Miguel Torga Secondary School - Lisbon, Alexandre
Herculano Secondary School - Porto).
One of the northeast Portugal high school students, in the Lymphocyte Physiology
Group.
Summer Placements
(Collaboration between IGC and city councils of Bragança district)
The third edition of the summer placements for northeast Portugal final
year students hosted five students, from three towns, in three IGC research
groups (Lymphocyte Physiology, Epigenetic Mechanisms, Telomeres and Genome
Stability). Students developed mini-projects under direct supervision
of IGC researchers, and presented and discussed their findings with their
peers and IGC scientists. Students' said, "Learning new concepts made this
week awesome and under the. We learnt many things that will be useful in
the future".
Poster of Gripenet awareness, for the 2001/12 campaign, aimed at recruiting
volunteers for the online flu-monitoring survey.
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Science Projects Support Programme
Since 2009 the science communication team works with IGC researchers to
provide supervision, theoretical and experimental guidance to secondary
school students carrying out science projects. In 2011, we worked with six
groups of students, organising visits to IGC facilities (Drosophila and rodent
facilities), discussions with scientists (neuroscience, Drosophila genetics,
bioinformatics), providing experimental and in-class protocols (in embryology,
microbiology, biodiversity, genetics).
Biology in Modern Times Seminars for Teachers
Targeted at secondary school science teachers, the Biology in Modern Times
seminars aim to update teachers on current research questions, techniques
and developments in the life sciences. IGC scientists, from PhD students
to the director, led informal presentations with Q&A on immunology, developmental
biology, evolution, neuroscience and bioinformatics. Up to 23
teachers, mostly from the Greater Lisbon area, attended each session. The
sessions were positively evaluated by the teachers.
'Aqui há Ciência' for Primary School Teachers
We are developing in-class activities and teacher-training for pre- and primary
schools. The project uses enquiry-based learning, which aims to recapitulate
the scientific process in each activity: observation, questioning, experimenting,
registering, concluding and communicating. Two local primary
schools are involved: 44 teachers and 798 students, over two years. In 2011
we developed and put in place a microbiology activity - Clean Hands, Dirty
Hands. All protocols will be available online.
Partners: Oeiras City Council, Instituto Superior Técnico.
Funding by: Oeiras City Council and QREN/PORLisboa (Portugal).
Online Education Resources
We are developing stand-alone educational resources for primary, middle
and secondary education. Our first animation - Me and My Body - introduces
and/or explores the concept of cells and the different research methods
used by scientists, including the use of animals in research. Targeted mainly
at 9-12 year olds, it is appropriate for all ages. This video won first place
in the Teaching Resources category of the international 2011 Ciência en
Acción Competition (Spain) , and has received 8,841 views on YouTube. Two
more videos, on evolution and genetics, are planned for 2012.
Funding by: Casa das Ciências (Portugal)
Researchers' Night 2011 - Noite dos Investigadores 2011
For the fourth year running the IGC was a partner in European Researchers’
Night. IGC scientists discussed their research with visitors and the science
communication team carried out evaluation of impact on the public and participating
researchers. Questionnaire-based surveys were designed, carried
out and analysed. Noite dos Investigadores 2011 took place in 15 cities across
Portugal, reaching over 10,000 on-site visitors.
Jardim Porcelânico - an artist in the laboratory
During his residency at the IGC, British artist Rob Kesseler used a range of
microscopy techniques to explore the micro-structures and cellular patterns
of Portuguese wildflowers. The result was a series of powerful, high chroma
images that were translated into large metre-wide prints (Morphogenesis
@ IGC, February 2011) and a porcelain collection produced in collaboration
with Vista Alegre Atlantis (Jardim Porcelânico @ FCG February 2011, British
Council March 2011, School of Pharmacy July 2011).
Collaborators: FCG UK Branch.
Funding by: FCG Joint Fund
C2 - scientists and artists exchange
The IGC and the FCG Modern Art Centre (CAM) joined efforts in the C2 programme
of visits and informal seminars, aimed at fostering an exchange of
perspectives and views between scientists and artists. Three artists (Rui
Sanchez, Didier Fiuza Faustino and Miguel Palma) described and discussed
their work at the IGC; three scientists (Thiago Carvalho, Élio Sucena, Nuno
Moreno), led tours of the artists' shows at CAM, and CAM-guided tours were
provided specifically for IGC staff and friends.
A still of the 'Me and My Body' award-winning animation.
British artist Rob Kesseler’s Jardim Porcelânico, at the Gulbenkian Foundation.
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Scientists Attitudes to the Use of Animals in Research
Working from the premise that knowledge of the scientific community's
attitudes towards animal research, and towards communicating this type of
research to the public and policy-makers should underlie any public engagement
programme, we have carried out a questionnaire-based survey of the
biomedical research community in Portugal. Data from the sample of 598
valid questionnaires, from 45 biomedical research institutes, is being analysed
for correlations between scientists’ experience with animal research
and their attitudes to regulation, practice and public engagement around
this issue.
Collaborators: IBMC (Porto), Observa (Italy)
Gripenet (Since 2009, part of the FP7-funded project, Epiwork)
Gripenet is a syndromic surveillance system that monitors the activity of
influenza-like-illness (ILI), in near-real time, with the help of volunteers, via
internet-based questionnaires about flu symptoms. The system includes a
broad range of science communication and education activities. In 2011,
Gripenet developed an online application for children (aged 6 to 12), that
allows data collection from this age group and from parents. Gripenet also
organised a schools cartoon competition.
Social Networks and New Media
Between June and December 2011, the IGC website received 429,109 visits
(average of 1,756 visits per day). In 2011 we continued to use new media
and social networking to communicate effectively with broad audiences, by
providing regular updates on research developments and outreach, in both
English and Portuguese:
• Facebook (9,277 fans as of December 2011)
• Twitter (around 1200 followers as of December 2011)
• YouTube (16 movies, around 23,000 views as of December 2011)
Teachers from two primary schools in Oeiras receive training to apply enquirybased
science learning with their students, in the Aqui há Ciência project.
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FUNDRAISING
Maria João Leão Head
PhD in Cancer and Virology, University of London, UK, 2004
Head of service since October 2010
The IGC develops an in-house programme aimed at raising private funds for
science through fundraising initiatives with private companies, charities and
the general public.
MAJOR PROJECTS AND ACCOMPLISHMENTS
THE IGC - EVERYTHING IS NEW (EIN) PARTNERSHIP
This unique partnership was established in 2008 between IGC and Everything
is New, promoter of the OptimusAlive! Oeiras music festival. Its main aim is to
bring science closer to Portuguese society and to raise funds for scientific research.
It is a strong example of how the private sector and society in general
may contribute to the progress of research and therefore to the future wellbeing
of all.
Optimus Alive Oeiras - IGC research fellowships
This partnership resulted in research fellowships that give young graduates
the opportunity to start their scientific careers, funded by Everything is
New. Over 300 young graduates around the country have applied to these
fellowships, since 2009. In 2011, Célia Rodrigues (25), and Diogo Santos (24),
were selected to develop one-year research projects in Biodiversity and Bioinformatics,
with the Population and Conservation Genetics and the Computational
Genomics IGC research groups, respectively. These projects are to
be carried out mainly at the IGC, and partly in Madagascar and France.
Public ceremony/ press conference at Calouste Gulbenkian Foundation (FCG)
28 June 2011
IGC and Everything is New organised a ceremony to mark the launch of the
OptimusAlive! Oeiras-IGC 2011 Fellowships and to reward previous fellows.
Diogo Lucena (FCG Trustee), António Coutinho (IGC Director) and Álvaro Covões
(EIN president) took part, as did previous OptimusAlive! fellows and IGC
group leaders, who presented their research. According to Álvaro Covões
“It’s a pity that more companies don’t follow our example, so that young
students are given a chance to improve our world”.
IGC presence at OptimusAlive! Oeiras11
6 - 9 July 2011
Science, Music and Art came together for the fourth year running during
OptimusAlive! Oeiras11. During the four days of this major music and arts
event the main activities at the IGC corner were speed-dating with scientists,
a Biodiversity game (adapted from an original idea of the IGC Population and
Conservation Genetics group) and a photo exhibition. Around 60 IGC volunteers
made these activities possible for the approximately 700 young people
that visited the IGC space during the four days of this event.
Collection of Delta sugar packs, for the IGC 50th anniversary.
Media and public impact
In addition to the high impact this partnership has shown in the media over
the years (2008-2011: 55 online articles; 28 print; 10 broadcast items), this
project has also been very successful in the social networks. A Facebook
page was created (380 likes) to advertise, describe and show videos and
pictures of the IGC initiatives carried out at the festival and the daily life of
the winners of the fellowships during their research projects, both at the
IGC and in Madagascar, Malaysia and Principe. Videos coordinated by IGC are
available through the IGC YouTube channel and give an insight into the IGC
activities at three different editions of OptimusAlive! Oeiras.
The IGC area at the OptimusAlive! Oeiras11 music and arts festival.
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COLEÇÃO CIÊNCIA - A PARTNERSHIP BETWEEN IGC AND VISTA ALEGRE
A collection of porcelain products, Coleção Ciência, is the result of a partnership
between the IGC and Vista Alegre, a prestigious and market leading
Portuguese porcelain manufacturer. The original images of this collection were
obtained by young scientists as part of their research at the IGC.
In 2011, the porcelain “Science Collection” became available at Vista Alegre
shops across the country, thus extending their availability beyond the Gulbenkian
Foundation shop, where they have been available since 2010.
Use of the funds from Coleção Ciência sales
Money raised through sales of the collection has gone towards scientific annual
meetings organised by the IGC PhD students and post-docs, together
with other funds raised in several fundraising activities (beer hours, S. Martinho
party, etc.) organised by the PhD students and post-docs themselves.
COLLECTION OF DELTA SUGAR PACKS
The IGC and DELTA Coffees celebrated their 50th birthday in 2011 and established
a partnership that led to a unique collection of DELTA’s sugar packs with
IGC images. DELTA produced three million sugar packs with seven different images
of the IGC, distributed across the country thus providing a vehicle to communicate
IGC research to a wide audience. DELTA also sponsored coffee breaks
at IGC events during 2011/12.
The winners of the OptimusAlive! Oeiras - IGC research fellowships.
Colecção Ciência, of espresso cups and mugs, in partnership with Vista Alegre.
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PARTNERS AND SPONSORS
Several partnerships and sponsorships have supported scientific research, education
and science communication and outreach activities at the IGC.
(The list below does not include funders of competitive calls for funding, outreach or networking).
ACTIMEL
ALFAGENE
AQUATIC SOLUTIONS
APPLICABLE ELECTRONICS, LLC
BIO-RAD
BIOGNÓSTICA
BIOPORTUGAL
CALOUSTE GULBENKIAN FOUNDATION
CÂMARA MUNICIPAL DE ANADIA
CÂMARA MUNICIPAL DE OEIRAS
CBD
CICLONE
DAGMA, LDA
DELTA Q
DIAS DE SOUSA
EMBNET
EMBO - EUROPEAN MOLECULAR BIOLOGY ORGANISATION
ENFIN
ENZIFARMA
EVERYTHING IS NEW
FRENCH EMBASSY IN PORTUGAL
FISHER SCIENTIFIC
GRUPO TAPER
ILC
CHAMPALIMAUD FOUNDATION
IZASA
LEICA
NORMAX
NYZTECH
PEPROTECH
PORTUGAL TELECOM (PT)
QUILABAN
ROCHE
SOCIEDADE PORTUGUESA DE BIOLOGIA DO DESENVOLVIMENTO
SOCIEDADE PORTUGUESA DE IMUNOLOGIA
STAB VIDA
STARSTEDT
TEBU-BIO
TECNIPLAST
THE EMBO JOURNAL
ULTRAGENE
UNICAM
VISTA ALEGRE
VWR
WERFEN GROUP
ZEISS
The IGC is under Scientific Sponsorship Law. This law provides tax benefits for
science-related donations by either individuals or companies.

We are grateful to everyone at the IGC - researchers, students and staff - who
supplied information, text and images used in this report.
EDITOR
ANA GODINHO
EDITORIAL ASSISTANT
ELIANA CARVALHO
PROOFREADING
CATARINA JÚLIO
ANA MENA
INÊS DOMINGUES
GRETA MARTINS
SHEILA VIDAL
MANUEL REBELO
LAYOUT AND DESIGN
DESIGNWAYS - WWW.DESIGNWAYS.PT
The Instituto Gulbenkian de Ciência Annual (IGC) Report is also available to
download from the IGC website at www.igc.gulbenkian.pt.
If you would like to receive a copy of this report, on a USB memory stick, please
contact:
Science Communication and Outreach
Instituto Gulbenkian de Ciência
Tel: +351 440 7959
Fax: +351 440 7970
E-mail: info@igc.gulbenkian.pt
This is an open access publication, and with the exception of images and
illustrations, the content may, unless otherwise stated, be reproduced free of
charge in any format or medium, subject to the following conditions: content
must not be used in a misleading context, the IGC must be credited as the original
author and the title of the document specified in the attribution.
The IGC was set up by the Calouste Gulbenkian Foundation, a Portuguese private
institution of public utility whose statutory aims are in the fields of arts, charity,
education and science. Created by a clause in Calouste Sarkis Gulbenkian's will,
the Foundation's statutes were approved in 1956. The head-office is located in
Lisbon.
First published by the Instituto Gulbenkian de Ciência, 2012
© Copyright Fundação Calouste Gulbenkian 2012