EuroBioForum II Connecting Life Sciences - European Science ...

EuroBioForum II Connecting Life Sciences - European Science ...

EuroBioFund: Conference ReportEuroBioForum IIConnecting Life Sciences5-7 December 2007, Lisbon,

European Science FoundationThe European Science Foundation (ESF) is an independent,non-governmental organisation of nationalresearch organisations.Our strength lies in the membership and in our abilityto bring together the different domains of Europeanscience in order to meet the scientific challenges of thefuture. ESF’s membership currently includes 77 influentialnational funding agencies, research-performingagencies and academies from 30 nations as its contributingmembers.Since its establishment in 1974, ESF, which has itsheadquarters in Strasbourg, with offices in Brusselsand Ostend, has assembled a host of research organisationsthat span all disciplines of science in Europe, tocreate a common platform for cross-border cooperation.We are dedicated to supporting our members inpromoting science, scientific research and sciencepolicy across Europe. Through its activities and instrumentsESF has made major contributions to science ina global context. The ESF covers the following scientificdomains:• Humanities• Life, Earth and Environmental Sciences• Medical Sciences• Physical and Engineering Sciences• Social Sciences• Marine Sciences• Nuclear Physics• Polar Sciences• Radio Astronomy Frequencies• Space SciencesEuroBioForumThe EuroBioForum is an annual forum where researchers,funding organisations and other stakeholdersthoughout Europe meet to discuss future life sciencespriorities. Identification of these life sciences topics isbased on ideas put forward by the life sciences communityand by public and private funding organisationsacross Europe via a Call for Expressions of Interest.Following a selection by an international SteeringCommittee, the programme for each workshop is thendefined in close collaboration with the proposers of theselected topic. The objectives of the workshop couldbe any or a combination of the following: i) to outline theplan for a new research programme, ii) to define a commonstrategic research agenda, or iii) to update currentfunders and sponsors and inform potential new ones.The workshops are organised in the frame of theEuroBioForum, where a number of other selected topicsare presented. In 2007, EuroBioForum II was heldon 5 to 7 December, in Lisbon, Portugal, in associationwith the Portuguese Foundation for Science and Technology(FCT) and the Portuguese Ministry of Science,Technology and Higher Education (MCTES). In 2008,the EuroBioForum will be held from 17 to 19 September,in Strasbourg, France in association with the FrenchMinistry of Research and Higher Education.EuroBioForum II was organised by EuroBioFund, anESF-led initiative that aims to support the coordinationof life sciences research funding in Europe. It is fundedby the European Commission’s Sixth Framework Programme(FP6) as a Specific Support Action undercontract number LSSG-CT-2005-019009.Cover: The Vasco de Gama Bridge, Lisbon, Portugal. © Noémia Costa Dias

2. Opening SessionJosé Mariano Gago John Marks Patrik Kolar Wouter SpekOpening SessionChair: John Marks, European Science FoundationJohn Marks, European Science Foundation,ESF and EuroBioFundJosé Mariano Gago, Portuguese Ministryof Science, Technology and Higher Education,The Lisbon AgendaPatrik Kolar, European Commission,EuroBioFund: Building the ERA in Health ResearchWouter Spek, EuroBioFund,Connecting Europe’s Unmet NeedsTo help coordinate the efforts of life sciences researchfunders, the EuroBioForum contributes to the developmentof the European Research Area (ERA).EuroBioForum II was organised as an event under thePortuguese Presidency of the European Union and theopening session included addresses by Professor JoséMariano Gago, the Minister for Science, Technologyand Higher Education; Dr. John Marks, Chief Executiveof ESF; Dr. Patrik Kolar, Head of Unit of Genomics andSystems Biology at the European Commission; andDr. Wouter Spek, Director of EuroBioFund.Dr. John Marks opened the conference with anintroduction to the background of the EuroBioFund inthe broader context of ESF’s mission. This includeda brief summary of ESF as a forum for its MemberOrganisations to have discussions on joint strategiesand collaborative actions to advance European scienceand explore new directions for research at the Europeanlevel. In undertaking these activities, ESF servesthe needs of the European research community in aglobal context.Key instruments, such as Forward Looks and theEUROCORES (European Collaborative Research)Scheme are central elements in ESF’s strategy,described in the ESF Strategic Plan 2006-2010 1 . ForwardLooks, for example, are a foresight-type activitywhich enables policy makers from ESF Member Organisationsin interaction with the scientific community,to develop medium- to long-term views and analysefuture research developments with the aim of definingresearch agendas and priorities for improved sciencepolicies at national and European levels.Dr. Marks emphasised the importance of workingwith ESF’s 77 Member Organisations, which togetherfund approximately 25 billion euro of research eachyear.In the areas of life and medical sciences, oneaspect of this work is the EuroBioFund, which aims to‘organise the scientific community to articulate majorinitiatives in the life sciences that are beyond the reachand scope of national funding agencies’. Involving otherfunding sources was also key to leveraging sufficientfunds to eventually develop large-scale transnationalresearch programmes.EuroBioFund is ‘an experimentin a new way of defining large scalescience in the life sciences…in joining funding from a varietyof sources’Dr. John MarksReferring back to a Nature editorial that was publishedat the launch of the EuroBioFund in January2006, Dr. Marks reminded the audience of the articlewhich stated that ‘the EuroBioFund is a positive signof the Commission’s willingness to generate ideas forthe European Research Area and serve as a catalyst 2 .It may end up being just a small step towards the ideal,but it is the biggest single step that we have seen forsome time’. Dr. Marks hoped that the EuroBioForumwould give rise to a number of activities and called onEuropean agencies to give it their full support.1. Editorial, Nature 2006, Jan 19;439(7074):2446 | EuroBioFund: Conference Report

Professor José Mariano Gago described severalimportant achievements made since the launch of theLisbon Agenda in 2000. This included the securing ofthe Seventh Framework Programme (FP7) (2007-2013)with a budget of 53.2 billion euro, representing anincrease of 63% on the previous Framework Programmeat current prices.There is a stronger emphasis on research themes,such as space, energy and health, along with a moreflexible and responsive programme to the needs ofindustry, which is essential because increasing theinvestment from the private sector is a key element ofthe Lisbon Agenda. With the European Research Council(ERC), recently established as an Executive Agency(14 December 2007), the EC now supports, for the firsttime, bottom-up research at the frontiers of knowledgebased on individual excellence.However, EC funding represents only a small portionof the total spending on research in Europe, andso efforts are now focusing on the internationalisationof national research funding. It is not relevant forevery research area but where it is necessary to bringtogether a critical mass of resources and expertise,horizontal strategies should be supported.There are however, many challenges, including legalhurdles, different funding and evaluation systems, andthe alignment of varying national interests. Furthermore,combining national public funding with private sources,either from foundations or industry, brings another levelof complexity. In addressing this challenge, the Euro-BioFund, must convincingly demonstrate that it candevelop new models of combined funding, and that it isindeed a better model than what already exists. It is alsoimportant to collaborate with other organisations workingon coordinating life sciences funding in Europe.As a platform for its 77 Member Organisations, ESFis ideally placed to do this. Speaking on the recentprogress in research-performing organisations workingtogether politically, including the German Max-Planck-Gesellschaft, the Spanish National Research Council(CSIC) and the French National Centre for ScientificResearch (CNRS), Professor Gago added that therenow exists an ‘extraordinary opportunity’ to build onthis new type of trust. ESF must also continue to workclosely with the European Heads of Research Councils(EUROHORCs).Professor Gago ended by saying that ‘ESF must notfail this time. We must give it full support to ensure thatthis initiative is a success’.Dr. Patrik Kolar provided more detail on recentachievements in developing the ERA and explainedwhy supporting initiatives such as the EuroBioForum isa priority for the EC.Dr. Kolar reviewed the important recent milestonesfor the ERA in 2007, including the launch of the firstcall for proposals for FP7, the development of ERA-NET-plus schemes and the agreement by the Councilof Ministers on four Joint Technology Initiatives (JTIs),including one on Innovative Medicines (IMI). JTIs areestablished on the basis of Article 171 of the EC Treatywhich allows the Commission to set up Joint Undertakingsfor ‘the efficient execution of Community research,technological development and demonstration programmes’.IMI forms a public-private partnershipbetween the EC and the European Federation of PharmaceuticalIndustries Associations.Dr. Kolar then spoke about the role the EuroBioForumhas in the ERA, which ‘has already proven its valueas a discussion platform, bringing new mature ideasfor research programmes in life sciences directly to thenational and European funding agencies’.There are still many questions to be answeredincluding: i) how to streamline individual strategies ofdifferent research funding agencies into a coherentplan at the European level, and ii) how to better coordinateEuropean, national and regional efforts in orderto overcome the fragmentation and avoid unnecessaryduplication. The best way is through dialogue and inthis way the EuroBioFund can help make a contributiontowards answering these tough questions.These research topics ‘revealthe strong global dimensionof life sciences today and placeEuroBioForum itself on a global level’Dr. Patrik KolarThe first session was closed by Dr. Wouter Spekwho spoke about the background to EuroBioFund andits key objectives. The EuroBioFund developed froma key recommendation of a 2004 European Commissionconference (Funding Basic Research in the LifeSciences: Exploring Opportunities for European Synergies),which urged that an annual funders’ forumbe established to discuss the new challenges in thelife sciences with the scientific community in order toagree on the best funding strategies to address them 3 .This is precisely what EuroBioFund has been striving todo with the annual EuroBioForum in the life sciencesarea.Dr. Spek explained that the EuroBioFund is basicallyabout networking and sharing information; morespecifically, it is about cross linking networks and gettingstakeholders together to address unmet needs.A greater focus on networking is an essential step3. Conference Report | 7

2. Opening Sessiontowards more sustainable financing, which is aboutidentifying and securing potential financial sources fora longer period of time.The financial landscape for life sciences researchis changing in Europe. Charities and foundations, nowrepresented by the European Foundation Centre 4 , areplaying an increasing role in setting research agendas.The EC and the European Investment Bank have developedthe Risk Sharing Finance Facility (RSFF) as partof the Seventh Framework Programme, which will useloans as a tool to support R&D and innovation 5 .‘EuroBioFund was set up by theEuropean Science Foundation (ESF)to take steps to bridge the gapbetween finance and life sciencesresearch’Dr. Wouter SpekIn conclusion, Dr. Spek encouraged participants toactively participate in the workshops and so take thefirst steps in initiating and facilitating strategic alliancesto develop joint strategic research agendas and activitiesin these key areas of life sciences research.4. www.efc.be5. | EuroBioFund: Conference Report

3. KeynotesThomas HudsonMichael TaussigThe two keynote speakers provided an insight into thekey challenges involved in organising and running largelife science consortia. Dr. Thomas Hudson, Presidentand Scientific Director, Ontario Institute for CancerResearch, Canada, spoke about a nascent consortium,which aims to generate a comprehensive descriptionof the ‘-omics’ changes in 50 different tumour types orsubtypes. Why is such a consortium necessary?Cancer is one of the leading causes of death in theworld, causing 7.6 million deaths in 2005 (WHO). Basedon projections, cancer deaths will continue to rise withan estimated 9 million people dying from cancer in2015, and 11.4 million dying in 2030. What is neededis a way to accelerate the identification of the geneticchanges in cancer, to enable the identification of newtherapeutic strategies. The broad goals of cancergenomics research can be summarised as: i) identificationof genome changes in tumours that drive cancerprogression, ii) discovery of new targets for therapy,and iii) drug selection based on the genomics of thetumour.A number of pilot studies on cancer genomicshave been undertaken that demonstrate the strengthsof using large-scale genomics. In John Hopkins University,a group sequenced about 13 000 genes intumour tissues from colorectal and breast cancerpatients. They reported finding potentially significantmutations in nearly 200 different genes, demonstratingthe enormous heterogeneity that exists both withinand across tumour types, which may explain the challengesin treating patients effectively 6 . Several lessonshave been learned from such pilot studies, includingthe importance of sample quality and the high rate ofabnormalities within tumours.6. Wood L D et al, Science 2007, Nov 16;318(5853):1108-13To lay the groundwork for the proposed InternationalCancer Genomics Consortium (ICGC), a meetingwas called by several supporting organisations, includingamong others, the Ontario Institute for CancerResearch, Genome Canada and the National CancerInstitute (USA) in October 2007 to exchange knowledgeand discuss opportunities for developing a consortiumthat would generate a comprehensive atlas of genomicabnormalities in cancer.Explaining the rationale behind such an ambitiousinternational initiative, Dr. Hudson pointed out that thescope was so huge that no country could generate acomprehensive database for all tumours. In additionit would help minimise duplication of efforts, whilstincreased standardisation could allow the merging ofdatabases and the detection of additional targets.A number of challenges face the setting up of theICGC consortium such as: data management; samplequality, size and informed consent; intellectualproperty; and publication policy. Overcoming thesechallenges would enable the generation of a comprehensivecatalogue of somatic changes in major cancerswhich would be a ‘powerful driver for cancer researchand clinical practice for decades’. Early clinical benefitswould be the stratification of tumours to allow betterprediction of prognosis and response to therapy andlonger term benefits would be the development of newand more effective targeted therapies.Dr. Michael Taussig, Head of the TechnologyResearch Group, The Babraham Institute, Cambridge,United Kingdom, spoke about an already establishedconsortium, ProteomeBinders. ProteomeBinders is aEuropean consortium that aims to establish a comprehensiveinfrastructure resource of binding molecules fordetection of the human proteome, together with toolsfor their use and applications in studying proteomefunction and organisation. A FP6 Research Infrastruc-EuroBioFund: Conference Report | 9

3. KeynotesFig 1. Immunofluorescence of protein expression in human celllines: a) protein kinase anchor protein; b) renin receptor precursor(from the Human Protein Atlas, Coordination Action, ProteomeBinders began inMarch 2006 and links 26 EU partners together with twopartners from the United States 7 .Binding molecules, e.g. antibodies, are among themost essential reagents in biomedical research and anarea where Europe has made breakthrough achievements.It is essential to create – for the first time – acomprehensive, standardised binder collection. Thesetools could then be used to explore protein expressionand function in health and disease.emphasised the importance of ‘creating a gold standardfor binder quality control and validation’.It was outlined how a European binders infrastructurecould operate. It would involve as a central corea ‘validated binder collection’, which would be subjectto quality controlled production (new and existing) atvarious centres in Europe. There would also be a majordatabase linked to the ‘validated binder collection’ witha tool box of technologies, to lead to the generation ofnew knowledge of the proteome.Despite the challenges of the programme, the benefitsof having such an infrastructure in Europe wouldbe three-fold: i) access: for proteomic researchers toessential tools; ii) discovery: definition of new drugtargets and biomarkers, which could feed into thebiotechnology and pharmaceutical industries; and iii)applications, e.g. to biobanked samples.‘Turning ProteomeBinders intoa full-blown large scale reagentgenerationprogram can drivethe field and incite additional effortsin and outside Europe’Editorial, Nature Methods, January 2007 8 .Addressing the question ‘What is proteomics?’it was defined as being the expression, localisation,interactions, modifications, actions and structure of allproteins. While the human genome has approximately24 000 genes, it is estimated that the number of proteinscould be anywhere in the region of 10-100 timesthis. Another challenge, in addition to the number ofundiscovered proteins, is the low concentration ofmany proteins, such as interleukins, so that highlysensitive protein detection methods are required. Currently,only a very small part of the proteome is coveredby available binding molecules, e.g. antibodies. As aresult a large number of new binding molecules arerequired and must be linked with protein-detectiontools capable of high sensitivity, wide dynamic rangeand multiplexing.As Dr. Hudson described in his talk, standardisationis a key issue for ProteomeBinders, and Dr. Taussig7. Editorial, Nature Methods 2007, Jan;4(1):1-210 | EuroBioFund: Conference Report

4. Brokerage SessionsPlenary and Brokerage SessionsPlenary Chair: Wouter Spek, EuroBioFundBart Sangster and Jos Kleinjans, A Future withReduced Animal Testing (ASAT)Jerome Weinbach, Preparing Europe for the NextViral Outbreak (V2 Task Force)David Nutt, Tracing the Pathways of Mental Illness(METPETS)Alain Tedgui, The European Vascular BiologyInstitute (EVBI)Christopher Bayliss, Combating BacterialPathogenesis and Antibiotic Resistance (GVG-NET)Roel van Driel, Systems Biology to CombatMetabolic Syndrome (SBMS)Rapporteurs:Fiona Kernan (ASAT, GVG-NET),Sandra Pinto-Marques (V2 Task Force, SBMS),Catarina Resende (EVBI, METPETS).The central focus of the EuroBioForum was the presentationof six research topics that were first introducedin a plenary session to the EuroBioForum participantsand developed further in dedicated parallel workshops.The workshops were attended by between 15 and 35representatives from research-funding organisations,industry, academic research institutions and governmentministries.4.1 A Future with Reduced Animal TestingThe afternoon plenary session of 6 December openedwith a presentation on ‘A Future with Reduced AnimalTesting’ by Professor Jos Kleinjans, MaastrichtUniversity, NL, and Dr. Bart Sangster, former SeniorVice-President, Safety and Environmental Assurance,Unilever, UK.The key objectives of Assuring Safety without AnimalTesting (ASAT) are: i) public health and environmentalprotection based on health risk assessment; ii) developmentof experimental models; and iii) generation ofdata and information for risk assessments, exploitingthe opportunities presented by new technologies.There is an increasing demand to eliminate animaltesting and generate improved data for risk assessment,based on societal expectations, changes toregulations (REACH; see box), and pressures on thepharmaceutical industry, where many new drug candidatesfail because of their high toxicity.Bart SangsterWhat is REACH?REACH is the new EU regulation on Registration,Evaluation, Authorisation and Restriction of Chemicals.It entered into force on 1 June 2007. The mainaims of REACH are to improve the protection ofhuman health and the environment from the risksthat can be posed by chemicals, the promotionof alternative test methods, the free circulation ofsubstances on the internal market and enhancingcompetitiveness and innovation. REACH requiresthe systematic testing of all chemicals that wereput on the market prior to 1981, as well as all newchemicals manufactured or imported in quantitiesgreater than 1 tonne a year (estimated to be 30000). this situation, together with recent advancesin ‘-omics’ technology and systems biology approaches,it was explained that a programme such as ASAT washighly feasible but was a huge effort, which wouldrequire investment and collaborations between partnersunaccustomed to working together.During the workshop, Dr. Sangster and ProfessorKleinjans presented more detailed information on ASATfrom its objectives and justification, to the proposedbusiness models for development and implementation,and debated various aspects of the programme withparticipants, including the next steps to be taken in2008.In his presentation, Dr. Sangster described theproposed model for implementation; a comprehensiveprogramme, managed by strong leadership with manyprojects carried out in parallel including developmentof new risk-assessment paradigms and identification ofEuroBioFund: Conference Report | 11

4. Brokerage Sessionsthe underpinning biological mechanisms, linked to newinsights from clinical medicine. He also reviewed thesupport that ASAT has received to date, including fromthe Dutch National Academy of Science, the NetherlandsGenomics Initiative and Maastricht University,the latter of which has offered to act as the hub forthe Netherlands network. Ultimately, ASAT has to be aninternational consortium and developed in opennessand transparency.‘Sooner or later this was supposedto happen: be bold and do it’Dr. Ben van Ommen, TNO Quality of Life, NLProfessor Kleinjans then presented further detailson the ASAT research programme, explaining thepotential application of toxicogenomics in the developmentof alternative testing methods. The potentialdeliverables include: i) in vitro assays for human hazardidentification validated in vivo, by interacting withclinical trials and pharmacotherapy, and by performingexploratory studies among human volunteers; and ii)a pan-European knowledge infrastructure for improvingenvironmental health through innovative and robustscience-based safety assessments of substances.In the discussions and reactions to the presentations,which were very positive, a number of issueswere addressed. The first was whether the objectiveof ASAT was to eliminate all animal testing. ProfessorKleinjans replied by saying that the primary aim is notnecessarily to do this, but rather to create a better scientificbasis for risk-assessment procedures. He added‘given the policy on alternatives, it is not about replacing,but also about refining and re-using’.With regard to feedback on the business planpresented, which was well received, one participanthighlighted that demonstration of affordability wasimportant. In response, Professor Kleinjans said thatthe business plan would explain the economic value incommercialising the research. ‘ASAT may play a role asan outsourcing partner for the pharmaceutical industries’he added. The importance of data collection wasalso raised by another participant, who pointed out thatthere were a number of huge projects in Europe with‘-omics’ databases. While agreeing with this point, ProfessorKleinjans added that the issues of data sharingand intellectual property would have to be addressed.Another participant commented that they were verypleased with the overall proposal but recommendedthat industry be involved at an early stage. There wasgeneral agreement on this, with an acknowledgementthat moving forward with industry – as advisers, notnecessarily as financiers – was a critical element forthe success of ASAT.In conclusion, ongoing Sixth and Seventh FrameworkProgramme projects in this field will be broughttogether in the first quarter of 2008. In parallel with this,there will be communication with industry-representativeorganisations to establish links. In addition to this,finance will be sought for the business plan and therewill be further workshops early 2008 in the Netherlandsto explore both the research programme and fundingpossibilities.4.2 Preparing Europe for the Next ViralOutbreakThe second speaker on the afternoon of 6 December,Dr. Jerome Weinbach from Inserm-Transfert, France,presented the V2 Task Force (Preparing Europe for theNext Viral Outbreak). This is a proposed pan-Europeanalliance to develop highly effective strategies againstpathogenic viruses. In his introductory slides he convincinglydemonstrated, through examples such asDengue fever, Ebola virus, hepatitis C and West Nilevirus, that infectious diseases are a significant threat tohuman health, causing approximately 15 million deathsworldwide each year.He then described the two strategies to combatviruses: vaccines and antiviral drugs. However, asDr. Weinbach pointed out, many viruses exist for whichthere is no effective treatment and, even for those vaccineswhich do exist, in the event of a pandemic, globalproduction capacity is inadequate.Against this background, the V2 Task Force aimsto form a network of networks fostering cooperationbetween highly productive, complementary consortia,for a comprehensive coverage of the antiviral drugissue. Among these networks would be two SixthFramework Programme projects, focused on antiviralresearch, VIZIER and VIRGIL.Jerome Weinbach12 | EuroBioFund: Conference Report

During the workshop, Dr. Weinbach, together withProfessor Jean-Louis Romette, University Aix-Marseille,France, described the objectives and structure of theV2 Task Force in greater detail, before opening the floorto comments and questions from participants.What are VIZIER and VIRGIL?VIZIER: this is a FP6 Integrated Project (2004-2008),involving 13 countries, with the objective of identifyingnew drug targets for RNA viruses, www.vizier-europe.orgVIRGIL: this is a FP6 Network of Excellence(2004-2008). The overall objective is to set up aEuropean Vigilance Network capable of addressingcurrent and emerging antiviral drugs resistancedevelopments, www.virgil-net.orgIn addition to the key objective introduced in theplenary session, the V2 Task Force would: i) link FP6networks to existing national schemes, global surveillanceschemes and organistions such as the WorldHealth Organisation (WHO), European Centre for DiseasePrevention and Control (ECDC); ii) provide thepharmaceutical industry with centralised managementof transnational clinical trials and surveillance, in vitro/in vivo models, biobanks and patient cohorts.Dr. Weinbach then described the four componentsof the network: i) surveillance (integrating existing clinicalsurveillance systems); ii) clinical virology (includingclinical trials and central repositories); iii) socio-economicimpact (impact of emerging viruses and drugresistance in terms of morbidity, monitoring andtreatment costs); and iv) drug search and evaluation(identifying new drugs or new combinations of drugs).Professor Romette, one of the coordinators ofVIZIER (see box) also highlighted the importance ofcapitalising on the biological banks, libraries and facilitiesthat have been created. He added that ‘we have tosave the valuable tools that have been created to date;otherwise they will be lost’. The discussions focusedon how the proposed consortia could be financed andit was widely accepted that the finance involved wassignificant. Various options were discussed includinglobbying national governments, foundations and internationalorganisations, securing European programmes,via the setting up of an ERA-NET and/or a Joint TechnologyInitiative on Antivirals (e.g. the EC InnovativeMedicines Initiative), and forming alliances with patientorganisations and scientific societies.There was a recommendation to focus on securingthe inclusion of the development of antiviral strategiesas a call topic, both at a national and European level.Although there was widespread agreement to involveindustry, there was a concern, expressed by Dr. Weinbach,that the research data generated would not befreely available to the wider research community.The issue of partnerships with countries in Africaand Asia was also raised and Dr. Weinbach highlightedthe importance of including countries fromvirus-endemic areas (e.g. China, Turkey, Central Africa).Transferring technology and best practices to lowerincomecountries in need would also attract additionalfunding and interest from the development agenciesand foundations (e.g. Bill and Melinda Gates Foundation).Dr. Weinbach closed the session with a summaryof the follow-up actions for 2008/9 and a commitmentto keep interested participants updated. These actionsinclude a meeting of the coordinators of topic-relatedFP6 programmes, which are ending (including VIZIERand VIRGIL), a development of a financial structure andthe potential launch of the network in early 2009.4.3 Tracing the Pathways of Mental IllnessProfessor David Nutt, University of Bristol, UK, wasthe final speaker for the afternoon plenary session.METPETS (Measuring Endogenous neuroTransmitterrelease in human brain with PET and SPECT tracers) isan ambitious programme, that looking for new ways toimprove our understanding of brain disorders and discovernew treatments. Professor Nutt presented starkfigures on the social and economic burden of braindisorders in Europe, which affect 127 million citizens,at a cost of almost 400 billion euro. He added that notonly was the incidence of brain disease increasing, butbrain mechanisms are so poorly understood, that ideasfor new pharmacological treatments are limited.David NuttEuroBioFund: Conference Report | 13

4. Brokerage SessionsMETPETS aims to address this vital health issue by‘developing technologies to allow us to ask questionsabout the nature of these disorders and hopefully leadus on the path to better treatment’. METPETS woulduse PET and SPECT (see box) to develop new technologiesto understand neurotransmitter function in thebrain. Although radiotracer imaging is a rapidly developingdiscipline for biomarkers of disease, in the lastdecade only one tracer for a neurotransmitter in thehuman brain has been developed, dopamine, whichhas revolutionised the understanding of addiction,schizophrenia and Parkinson’s disease.The benefits from developing tracers for disorderssuch as addiction, anxiety and depression, would bethree-fold: increasing our understanding of the diseaseprocess, providing new leads for drug discovery, andfacilitating clinical development.What are PET and SPECT?Positron Emission Tomography (PET) and SinglePhoton Emission Computed Tomography (SPECT)are part of a family of nuclear medicine imagingtechniques. They use radionuclide tracer techniquesthat produce images of the in vivo radionuclidedistribution with measurements made with an externaldetector system. SPECT uses radioisotopesthat emit gamma rays, such as thalium-101 andiodine-123, giving a resolution of 10-14 mm. PET,on the other hand, uses positron-emitting isotopesof carbon-11, oxygen-15 and fluorine-18, giving animproved resolution of 5-7 mm.Source: Lodge M A et al., Journal of InvasiveCardiology 2005, Sep 17(9), 491-6.In the workshop, Professor Nutt was joined bythree supporters who gave presentations on i) thestate of the art of neurotransmitter imaging and braindisease (Professor Gitte Moos Knudsen, CopenhagenUniversity Hospital, DK); ii) dopamine imaging andmeasurement in patients (Professor Marc Laruelle,GlaxoSmithKline, Imperial College London, UK); andiii) the European Brain Council (Professor Jes Olesen,President, EBC, Brussels, BE) who underlined hisstrong support for METPETS.What is the European Brain Council?The European Brain Council (EBC) is a coordinatingcouncil formed by European organisations inneurology, neurosurgery, psychiatry, basic brainresearch (neuroscience), as well as patient organisationsand industry. It represents a vast networkof stakeholders, working in close partnership withthe European Commission, the European Parliamentand the World Health Organisation (WHO), aswell as other decision-making bodies. The EBC wasofficially founded on 22 March 2002 in Brussels, andhas offices in Brussels and Florence.www.europeanbraincouncil.orgThe formal presentations ended with an overviewof the work of P1vital Ltd., a contract researchorganisation that specialises in developing precompetitiveacademic-pharma collabarorations inexperimental medicine for central nervous systemdisorders 9 . Dr. Gerry Dawson outlined the envisionedrole of P1vital Ltd. in METPETS.Among the issues raised during the open discussionwas that of sharing the risk of pre-competitiveresearch. There was general agreement that better andfaster progress was possible if industry would sharethe knowledge, and costs were shared between privateand public funding. This was reiterated by another participantwho said that ‘pre-competitive collaborationsare essential to facilitate drug discovery and avoidduplication of efforts’.Another participant questioned the expected costsof the programme. Professor Nutt replied that it wasdifficult to predict, but that the estimated cost pertracer was in the order of 5 to 10 million euro. He addedthat the consortium could spread the work needed in amore efficient way.‘Understanding neurotransmitterfunction, the language of the brain,is the key to understanding brainfunction’Professor David NuttIn his closing remarks, Professor Nutt announcedthat there would be two meetings in early 2008 toorganise the consortium further, and to design andelaborate METPET’s work plan.9. www.p1vital.com14 | EuroBioFund: Conference Report

During the discussions, strong support wasexpressed by both the British Heart Foundation (BHF)and the German Federal Ministry of Education andResearch (BMBF). [Support from the Netherlands HeartFoundation has already been expressed].Alain Tedgui4.4 European Vascular Biology InstituteAnother critical health issue for Europe is cardiovasculardisease, which is responsible for almost half of alldeaths in Europe (see box for further details). ProfessorAlain Tedgui, who heads a group in Paris working onthe role of cell death and inflammation in atherothrombosis,presented an ambitious and exciting proposalfor a virtual institute for vascular biology in Europe: TheEuropean Vascular Biology Institute (EVBI).The mission of this institute is to connect and coordinatethe leading groups in vascular biology researchand so develop new diagnostic and therapeutic treatmentsfor this devastating disease. These areas ofresearch would include developing novel approachestoward stabilising atherosclerotic plaques, searchingfor biomarkers to identify at-risk patients and exploringthe application of regenerative medicine in repairingdamaged heart tissue.To achieve these goals, Professor Tedgui argued thata pan-European structure was needed to assemble thenecessary critical mass of expertise and resources andfor keeping pace with increasing technological change.Importantly, EVBI would be starting from a basis of theSixth Framework Programme Network of Excellence(NoE), European Vascular Genomics Network (EVGN) 10 .During the workshop, Professor Alain Tedgui providedmore detail on the proposed institute, which heenvisages as a platform taking a systemic approachto cardiovascular disease. Central to the structurewould be a consortium of academic partners with keystakeholders involved including industry, patient organisationsand foundations.There was further information presented on theshort- and long-term objectives of EVBI, funding possibilitiesand the implementation plan. With regard tofunding, Professor Tedgui envisaged that the fundingwould be supported by three pillars: i) national fundingagencies, ii) private and public foundations/charities,and iii) drug/device companies.10. www.evgn.orgCardiovascular disease factsCardiovascular disease is a group of disorders of theheart and blood vessels and includes coronary heartdisease, peripheral heart disease, rheumatic heartdisease and deep vein thrombosis. Cardiovasculardisease is the primary cause of death among menand women in Europe with over 1.9 million deathsper year. It is estimated to cost the EU economy169 billion euro per year. At least 80% of prematuredeaths from heart disease and stroke could beavoided through healthy diet, regular physical activityand avoiding tobacco smoke.Source: World Health OrganisationAnother participant raised the question of openingup membership of EVBI to those outside the currentEVGN consortium. Professor Tedgui replied that atpresent, membership was limited to EVGN partners,but that this could change in the future.The issue of Intellectual Property (IP), which is criticalfor any involvement with industry, was also raised.Dr. Catherine Clusel, Inserm-Transfert, another coordinatorof EVBI, replied that a one-day meeting withthe pharma industry was being organised to discuss IP.She added that the current position was that the returnon investment should remain with the institutions thatcreate the IP.Professor Tedgui closed the meeting with a reviewof the follow-up actions, which include collectingsupport letters, defining the governing structure andelaborating the consortium agreement.4.5 Combating Bacterial Pathogenesisand Antibiotic Resistance (GVG-NET)The second speaker on 7 December was Dr. ChrisBayliss, University of Leicester, UK, who introduced aproposal to set up a European-wide programme forresearchers working on genetic variation generators(GVGs) in bacterial pathogens. GVGs, as Dr. Baylissexplained, are factors that increase the rate of productionof genetic variation in a bacterial genome and soenable bacterial pathogens to evade preventative andtherapeutic measure; examples of GVGS include mutators,repetitive DNA, recombination and lateral genetransfer.EuroBioFund: Conference Report | 15

4. Brokerage SessionsChristopher BaylissWhat are common bacterial pathogens?Neisseria meningitides: causes bacterial meningitisand is responsible for epidemics. In 2002, an outbreakin Burkina Faso, infected 13 000 people, killing1 500.Streptococcus pneumonia: causes many types ofinfection including pneumonia, meningitis and pericarditis.It is responsible for the deaths of at least1 million children each year.Mycobacterium tuberculosis: causes tuberculosis.In 2005, 8.8 million people fell ill with TB and 1.6 milliondied.Source: World Health OrganisationGVGs are in all key bacterial pathogens (see boxfor examples), which are significant causes of illnessand mortality worldwide. Given this and other factors,including the rise in antibiotic resistance, and the currentexplosion in genomic data, Dr. Bayliss emphasisedthat the timing was right for launching a major Europeaninitiative on GVGs in Europe.The aims of GVG-NET are four-fold: i) to set up aEuropean-wide networking scheme for GVG researchers,ii) to standardise techniques for studying GVGs, iii)to develop an infrastructure for dissemination of GVGdata, and iv) to assess the contributions of GVGs toantibiotic resistance, spread and virulence of bacterialpathogens, and to genome diversity.In summarising the two-hour workshop session,there were presentations by other members of theGVG-NET consortia, to provide further detail on thescience, discussions on the outputs of GVG-NET andan outline of the next steps to be taken to realise thegoals of this consortium.Dr. Alex van Belkum, Erasmus Medical Center,NL, spoke about molecular typing and repetitive DNA;Professor Tone Tonjum, University of Oslo, NO, gavea presentation on transformation and its contribution tothe pathogenicity of bacteria, including Neisseria meningitidis,the meningococcus. Professor FernandoBaquero, Ramon y Cajal University Hospital, Madrid,ES, ended with a presentation on mutators and antibioticresistance. Another important task is to identifyand predict the possible evolutionary trajectories ofmicroorganisms in particular environments.Following these presentations, Dr. Bayliss thenreviewed some of the outputs that would result fromGVG-NET. These would include: i) fundamental research(i.e. identification of novel GVGs), ii) applied research(i.e. finding new drug targets), and iii) databases (i.e.current GVGs). To illustrate the potential for developinga database, a presentation was made by Dr. ClausLundegaard, Technical University of Denmark, DK.The discussion was then opened to the floor. In adirect comment on Professor Baquero’s earlier presentation,one participant remarked on the issue of raisingawareness among medical doctors of the importanceof taking regular samples from patients, to track theevolution of bacteria. In response, Dr. Bayliss, said thatsuch a comment highlighted the need for a network;‘we need much more discussion, and there needs tobe an inflow of ideas from those working on the fundamentalscience area and those in the clinical area, sothat both sides can understand the critical issues’.A pharmaceutical representative questioned thebenefit for industry, and asked how the knowledgecoming out of such a consortium on GVGs could bebeneficial. In response, Professor Tonjum said that antimicrobialpeptides were an excellent example of a drugthat could be developed using knowledge of GVGs.There was significant interest expressed by a numberof the companies present to become involved in bothpilot studies and database development.‘Genetic Variation Generators (GVGs)are an important and fundamentalresearch topic, also of relevanceto cancer development, ageingand neurodegenerative diseases’Professor Tone TonjumOne participant recommended that the proposersfocus on the management structure and carefully considerthe necessary elements for a sustainable network.This was reiterated by a number of other participants.In his summary remarks, Dr. Bayliss said that potentialpartners had been identified, and that the key issueof developing a strong business plan would be circulatedto other members of the group, so that GVG-NETcould be taken a step further in the coming months.16 | EuroBioFund: Conference Report

4.6 Systems Biology to Combat MetabolicSyndromeThe final research topic presented was ‘Systems Biologyto Combat Metabolic Syndrome’ (SBMS), by ProfessorRoel van Driel. Metabolic syndrome is a cluster ofclinical disorders, including obesity, insulin resistanceand hypertension, which is on the rise in Europe. Givenits prevalence, metabolic syndrome has a significantsocietal and economic impact. To effectively addressit, SBMS proposes a novel joint European programmeover a period of 10 years, which will combine the rapidlygrowing systems biological expertise with biomedicalresearch efforts on metabolic syndrome.SBMS’s key objective is to develop a true understandingof the syndrome, to allow the development ofrational and effective therapies. As Professor van Drielsaid: ‘understanding’ means knowing how the networksof molecules cells and tissues interact in timeand space, developing predictive quantitative modelsfor metabolic syndrome and gaining an insight into theunderlying principles of the networks.What is Metabolic Syndrome?Metabolic syndrome has been described as a ‘clustering’of several risk factors for cardiovascular disease,namely obesity (particularly abdominal obesity),abnormal blood lipids (dyslipidemia), insulin resistanceand high blood pressure (hypertension). Thereis no universal definition for the metabolic syndromeand differences exist in the criteria used to diagnosethe presence of the metabolic syndrome. One measurementfor diagnosis relies on waist circumferenceand blood triglyceride level. This has been called a‘hypertriglyceridemic waist’ and for men is diagnosedas a triglyceride level greater than 2 mmol/l and awaist circumference greater than 90 cm.Source: World Health OrganisationProfessor van Driel pointed out some of thechallenges involved including the complexity of thesystems, data integration and the current fragmentationof research in Europe, but was confident that, withstrong research management and coordination, theycould be overcome.During the workshop session, there was a lively discussionon many aspects of the proposed consortium.Professor van Driel began the session by reviewing theenvisaged road-map for SBMS, which comprises fourphases: i) develop the governance structure and agreeon milestones, ii) start pilot research programme, iii)expand research activities, and iv) execute full-scaleresearch programme.Roel van DrielOne participant raised the issue of the quality ofpatient and clinical data, and recommended that a preparatoryphase be put in place to address this, by forexample, developing Standard Operating Procedures(SOPs). EUMORPHIA, a FP5 programme, which establisheda three-tier system for their SOPs, was cited asan excellent example.A comment was made that there needed to be decisionstaken on how many patients should be recruitedand for how long they should be followed-up.With regard to the composition of the consortium,after a brief debate, there was agreement that industryshould be involved from an early stage. Professor vanDriel also emphasised the importance of having cliniciansworking on metabolic syndrome who, althoughthey were not present at the session, had been contactedand expressed an interest. Regarding theadvisory board, there was agreement that it shouldconsist of worldwide experts, and not be limited toEurope alone.There was an enthusiastic response to the suggestionto have a number of workshops, which would focuson the different aspects of the consortium, includingfunding, establishing patient lists and planning the pilotprojects. Several participants expressed an interest insupporting them financially, pending an elaboration ofthe workshop themes.In closing the workshop, Professor van Driel saidthat this would be done early in 2008, in parallel withan expansion of the consortium to include all relevantrepresentatives.EuroBioFund: Conference Report | 17

5. Concluding SessionStanislav Ehrlich Closing Session Edvard BeemConcluding SessionPlenary Chair: Wouter Spek, EuroBioFundBart Sangster and Jos Kleinjans, A Future withReduced Animal Testing (ASAT)Jerome Weinbach, Preparing Europe for the NextViral Outbreak (V2 Task Force)David Nutt, Tracing the Pathways of Mental Illness(METPETS) [replaced by Wouter Spek]Alain Tedgui, The European Vascular BiologyInstitute (EVBI)Christopher Bayliss, Combating BacterialPathogenesis and Antibiotic Resistance (GVG-NET)Roel van Driel, Systems Biology to CombatMetabolic Syndrome (SBMS)John Marks, European Science FoundationThe concluding session provided an opportunity for theleaders from each research topic to give feedback onthe brokerage sessions to all conference participantsand short summaries of the envisaged follow-up activitiesin the short term.Professor Jos Kleinjans (Assuring Safety withoutAnimal Testing, ASAT) summarised that the workshophad been very useful, with a clear expression of interestfrom participants. The first step in 2008 will beto organise a meeting to bring all relevant Sixth andSeventh Framework Programme projects together, anddevelopment of the ASAT website as an instrument ofcommunication.Based on feedback from participants during theworkshop on the viral task force for Europe (V2 TaskForce), the plans for the coming year will be modified.The national funding agencies will continue to belobbied, with a possibility of using the French Presidencyof the European Union to highlight the proposal(June-December 2008). A consultation with the majorpharmaceutical players will also be undertaken toestablish the basis for a partnership.Speaking on behalf of Professor Nutt, Dr. Spekreported that the output from the workshop on ‘Tracingthe Pathways of Mental Illness’ (METPETS), will be twomeetings in the first half of 2008. The first will aim tofully elaborate the proposal, with the setting up of theproject management team and securing of other partners;and the second to formalise the research plan.Potential funding will be explored at a European level,possibly through the Innovative Medicines Initiative,and through future partnerships with pharmaceuticalcompanies.The follow-up actions for the virtual institute toaddress cardiovascular disease at a European level(European Vascular Biology Institute, EVBI) weresummarised. The first is to continue collecting supportletters, adding to those already received from theNetherlands Heart Foundation and the British HeartFoundation. There will be a one-day meeting betweenthe consortium and the industrial partners to exploreroutes for partnership and a meeting of the academicresearch centre to define the legal structure for EVBI.In early 2008, there will be a follow-up workshopto clearly define the scientific scope of the programmefor ‘Combating Bacterial Pathogenesis and AntibioticResistance’ (GVG-NET), another important public healthcare issue. Interest expressed by several potential partnerswill be followed up in the coming year.Professor Roel van Driel reported that the meetinghad set in motion a number of concrete actionsfor ‘Systems Biology to Combat Metabolic Syndrome’(SBMS). There was agreement to draft a white paper inmid-2008, using input from two proposed workshopsin March 2008 with researchers and interested fundingagencies. Forming a basis for communication to18 | EuroBioFund: Conference Report

6. Latest DevelopmentsEuroBioForum II aimed to bring together the researcherswith representatives from the pharmaceuticalindustry and funding organisations to assess how thepresented initiatives can best be supported. For atleast three research topics (of the six presented at theconference) positive progress can be reported.In January 2008, Professor David Nutt (METPETS)received support for two workshops from the MedicalResearch Council UK and the University of Bristol,UK. The aim of these workshops will be to: i) set upthe project management team, and ii) formalise theresearch plan. Professor Malcolm Anderson, the ProVice-Chancellor for Research at the University ofBristol said that ‘METPETS is an important initiativewhich hopes to pave the way for significant advancementsin research into the causes of mental illness. Iam delighted that it has received such positive supportfrom the European science community and the MRCand I look forward to seeing the initiative develop in2008’.Dr. Chris Bayliss (GVG-NET) also received supportfrom the Medical Research Council UK in January 2008for a workshop with the objective of defining the scientificscope of the programme. Dr. Mark Palmer, theHead of International Policy at the MRC said ‘GVG-NETis a promising initiative, addressing the critical issue ofunderstanding how bacterial pathogens mutate theirgenetic code, and the impact this has on the bacteria’santibiotic resistance and pathogenesis. EuroBioForumwas a first step in bringing together the researchersinvolved, with representatives from the pharmaceuticalindustry and funding organisations to provide input andadvice. The support from the MRC will build on this firststep, to facilitate interested parties in the process ofdeveloping GVG-NET’.On 28 February 2008 the coordinators of ASAT,Professor Jos Kleinjans and Dr. Bart Sangster, organiseda meeting of the coordinators of relevant FP6 andFP7 funded projects, including those on toxicology, animportant pillar of ASAT, in Milan, Italy. The aim wasto achieve an overview of the relevant programmesin Europe and the activities of the major internationalplayers in the field, to discuss the research needs andexplore ways of improving collaboration. A follow-upmeeting has been tentatively scheduled for September2008. For up to date information, refer to ASAT’s newlydeveloped website‘Science knows no country,because knowledge belongs tohumanity, and is the torch whichilluminates the world’Louis PasteurFor latest news: | EuroBioFund: Conference Report

AppendicesEuroBioFund: Conference Report | 21

Appendix I – AbstractsA Future with Reduced Animal Testing(ASAT)Preparing Europe for the Next ViralOutbreak (V2 Task Force)Kleinjans J. 1 and Sangster B. 21. Faculty of Health, Medicine and Life Sciences,Maastricht University, NL2. Former Senior Vice-President, Safety andAssurance, Unilever, UKThere is an increasing demand for better chemicalsafety management in the EU. In particular, there isa demand for the elimination of animal testing, moresafety data and a better way to deliver safety, forinstance within the context of REACH (a) . The arrivalof gene-based (genomics) technologies will changetraditional regulatory toxicology because it will generatemore insight into molecular mechanisms, theunderlying toxic mode of actions and dose-responserelationships, and will therefore impact on assessingno-effect levels and thus the basis of our currentapproach to establishing chemical safety. The objectiveof ASAT is to avoid data generation in experimentalanimals by adjusting current risk paradigms, by using‘-omics technologies’, transcriptomics, proteomicsand metabonomics in particular, modern informationand data management technologies, clinical medicineand systems approaches in biology. ASAT aims to initiatea think-tank which will develop novel theoreticalconcepts on chemical risk-assessment and from that,design correspondingly required changes in toxicologicalparadigms, thereby steering RTD activities. ASATfurther aims to develop and execute a ‘scientific multicentreresearch programme’ that will perform theseRTD activities in a coordinated way, thereby focusingon developing novel risk-assessment paradigms andtest models such as alternatives to current animal toxicitytesting. ASAT will create a ‘communication office’which will translate theoretical concepts and scientificresults into information accessible for regulators andthe general public, communicate with relevant usergroups and organise training activities. In order toeffectively use available toxicogenomics knowledgeand develop the applied systems toxicology paradigm,the ASAT programme will integrate relevant current FP6research programmes in the areas of toxicogenomics,chemical risk-assessments and alternatives to currentanimal models for toxicity testing.Weinbach J. 1 , Neyts J. 2 , Snijder E. 3 , Zoulim F. 4 ,De Lamballerie X. 5 and Canard B. 61. Inserm-Transfert, FR;2. Rega Institute, KU Leuven, BE;3. Leiden University Medical Centre, NL;4. Inserm, Lyon, FR;5. Faculté de Médecine de Marseille, FR;6. AFMB, Marseille University, FR.The V2 initiative aims at capitalising on the success ofFP6 networks (VIRGIL and VIZIER, hence V2) by buildinga world-class comprehensive task force on highlyeffective antiviral strategies against emerging viruses,as defined by novel pathogenic viruses or viruseswhose clinical importance is rising because of a seriesof factors that include, specifically, drug resistance(as defined in the 1992 American Institute of MedicineReport). This effort will build a long-lasting, comprehensiveconsortium capable of addressing all aspectsof research on antiviral drugs and encompassing allknown or emerging viral pathogens in an integratedand synergistic manner addressing pre- and ongoingpandemic situations. Activities will range from basicresearch on drug design, target identification, in vitro/in vivo models to translational clinical research forthe anticipation and understanding of drug-resistantviruses, and socio-economic strategies to effectivelyintroduce novel antiviral strategies. Moreover, the V2FP7 activity platforms (surveillance, clinical virology,drug target identification and models, pharmacology,host/pathogen interactions, technological innovation,socio-economic impact) will be supported by transversaltools and services including bioinformatics andmathematical support, legal and ethical expertise,support for clinical trials and studies, a training and disseminationworkpackage, a logistical service for largeconference organisation, and a business platform forindustrial contracts.(a) | EuroBioFund: Conference Report

Tracing the Pathways of Mental Illness(METPETS)The European Vascular Biology Institute(EVBI)Nutt D. 11. Psychopharmacology Unit, University of Bristol, UKWe propose to develop a groundbreaking programme,based on the measurement of neurotransmitter releasein the human brain using PET and SPECT tracers,which will significantly increase current knowledge ofhuman brain disorders from schizophrenia to addictionand could lead to the development of innovative newtreatments. PET and SPECT techniques are currentlythe only way in which endogenous neurotransmitterrelease can be measured. However, the challengesof developing new tracers are so massive that onlyan approach that brings together all the major Europeannuclear medicine centres will be successful. Thisprogramme of work will coordinate and integrate theundoubted expertise of the leading European centresto develop a focused programme for neurotransmittermeasurement. Achieving this goal will have a majorimpact on the understanding of mental illnesses includingaddiction, the most costly of all medical problemsin Europe and some of the least well served by currenttreatments – see Promoting the Mental Health of thePopulation: Towards a Strategy on Mental Health forthe EU (b) – which cites a study of Wittchen & Jacobi(2005) that estimates that over 60 million Europeansaged between 18 and 65 suffer these disorders. It alsowill help achieve the goals of the EU drugs strategy2005-2012 and the EU Action Plan on Drugs (c) throughdiscovering new approaches to treatment. In addition,new tracers will profoundly benefit the neurosciencecommunity in that they will allow fundamental hypothesesderived from pre-clinical studies about the role ofneurotransmitters in normal mental processes to beaddressed.(b) A. 1 (see below for other proposers) 21. Cardiovascular Research Center,Hospital Lariboisière, Inserm, Paris, FRThe European Vascular Biology Institute (EVBI) willprovide a structure for leading European groupsalready involved in research on vascular biology andmedicine, whose collaboration is currently supportedby the FP6 Network of Excellence EVGN (EuropeanVascular Genomics Network), created in January 2004.The common activity within the EVGN has been veryfruitful, producing more than 100 novel collaborationsbetween at least two EVGN partners. This is reflectedin the number of publications in high-ranking journalsemanating from collaborative studies, which has steadilyincreased since the creation of the EVGN. To furtherfoster integration of partners within the network as wellas the expansion of this grouping, three technologyplatforms were set up in 2005 and were fully operationalin 2006. The Bioinformatics platform in Amsterdam,the Proteomics platform in London, and the Zebrafishplatform in Milan offered cutting-edge technology,organised hands-on workshops and initiated severalcollaborative projects within the consortium, focusedon the rapid identification of novel molecular targets. Inlight of the achievements of the EVGN, the consortiumpartners propose to create a virtual institute for vascularbiology and medicine (EVBI) to perpetuate beyondthe FP6 funding, the quality and excellence alreadygathered within the EVGN. The EVBI will seek to securethe necessary critical mass and accelerate multidisciplinaryinteractions by uniting world-leading basic andclinical institutions from European countries. It will be atthe forefront of research in vascular biology and medicine,and will participate in the opening and explorationof novel areas of therapeutic potential in cardiovasculardisease. The EVBI will permit us to go a step furthertowards drug discovery by inviting pharmaceutical andbiotech companies to join the academic groups.2. Bennett M. (UK), Binder B. (AU), Clusel C. (FR),Daemen M. (NL), de Vries C. (NL), Dejana E. (IT),Dimmeler S. (DE), Fleming I. (DE), Hansson G.(SE), Levy B. (FR), Martin J. (UK), Newby A. (UK),Struijker-Boudier H. (NL) and Zeiher A (DE).EuroBioFund: Conference Report | 23

Appendix I – AbstractsCombating Bacterial Pathogenesisand Antibiotic Resistance (GVG-NET)Systems Biology to Tackle MetabolicSyndrome (SBMS)Bayliss C. 1 , Tonjum T. 2 and van Belkum A. 31. University of Leicester, UK2. Institute of Microbiology, University of Oslo, NO3. Erasmus Medical Centre, Rotterdam, NLGenetic variation can be generated by transformation,conjugation, mutation or localised hypermutation ( DNA repeat tracts). Many bacterial pathogens exhibitstrain-to-strain variations in the rate of generation ofgenetic variation by each of these processes. Thesestrain-to-strain variations are due to differences in thepresence and function of specific DNA sequences andgene products (‘the genetic variation generators’; GVGs)responsible for mechanistic generation of genetic variation.Understanding the extent of variability is importantas genetic variation contributes to persistence of bacterialpathogens in their hosts, to their avoidance ofintervention strategies (e.g. vaccine-induced immuneresponses and antibiotic treatment) and to virulence.Studies in some pathogens have revealed an elevatedglobal mutability in disease-associated isolates, ‘mutators’,that is associated with mutations in mismatchrepair genes. Although a general link between diseaseand mutator phenotypes is not yet established, DNArepair components are clearly involved in the mechanismsfacilitating genome fluidity and adaptation. Forintragenomic variation, the relative contribution betweenspontaneous mutation and horizontal gene transfer isnot known. There is therefore a requirement to extendour knowledge of strain-to-strain differences in generationof genetic diversity and to identify the ‘generators’responsible for these differences. This research willimprove our understanding of the balance betweengenomic instability and maintenance pathways and ofthe effects of GVGs on clinical outcomes of bacterialinfections. Studies of strain-to-strain variability and themechanistic basis for generation of genetic diversityhave and are being performed in multiple laboratorieswithin Europe but the data is dispersed and often collectedby different methods. This programme aims toinitiate a European-wide cooperative effort to standardisemethods, to provide databases for collation andcomparison of data, to generate further epidemiologicaland mechanistic data on GVGs and to assess thecontributions of GVGs to persistence, spread and virulenceof bacterial pathogens.van Driel R. 1 (see below for other proposers) 21. Netherlands Institute for Systems Biologyand University of Amsterdam, NLMetabolic syndrome consists of a cluster of interrelatedcommon clinical disorders, including obesity, insulinresistance, glucose intolerance, hypertension, anddyslipidemia. Metabolic syndrome develops as a resultof an imbalance of energy homeostasis, which leads toinsulin resistance and often develops into type 2 diabetes(T2D). T2D, obesity and lipid disorders are majorrisk factors for myocardial infarction and stroke.These cardiovascular complications are the primarycause of death in the Western world. In addition, diabetesis the main cause of loss of vision, renal failure andamputation of the lower extremities. Roughly 190 millionpeople are affected with T2D worldwide, a numberexpected to double in the next 20 years. In addition,there is an alarming increase in the number of childrenwho suffer from the traditionally age-related diagnosisof insulin resistance and T2D.Metabolic syndrome, like other multifactorial diseases,evidently is too complex to tackle along the linesof classic research programmes. Considering its impacton human well-being and our Western society, it callsfor a paradigm shift in biomedical research. Systemsbiology is a rapidly developing approach that systematicallyimplements the iterative cycle of data-drivencomputational modelling and model-driven experimentation,resulting in more rational, cost-effective andgoal-oriented scientific research. We propose to set upa pan-European programme, spanning a period of 10years, which combines the rapidly growing systems inbiological expertise in Europe with ongoing and newbiomedical research efforts in the field of the metabolicsyndrome, involving academia, industry, investors andcharities.2. Engel A. (CH), Groen B. (NL), Hohmann S. (SE),Klipp E. (DE), Priami C. (IT), Reuss M. (DE) andWesterhoff H. (UK)24 | EuroBioFund: Conference Report

Appendix II – Conference ProgrammeParallel Sessions15:30 - 17:30Session IA Future With Reduced Animal Testing (ASAT)Session IIPreparing Europe for the Next Viral Outbreak(V2 Task Force)Session IIITracing the Pathways of Mental Illness (METPETS)20 :00 - 23:00Dinner at the Cultural Centre of BelémFriday 7 DecemberPlenary Sessions8:45 - 9:45Introduction to Brokerage Session Topics4. The European Vascular Biology Institute (EVBI)Presented by Professor Alain Tedgui, CardiovascularResearch Center, Hospital Lariboisière, Inserm, ParisCardiovascular disease is the leading cause ofmortality in Europe, causing up to half of all deathsin some European countries and is estimated tocost the European Union 169 billion euro each year.This ambitious European collaborative effort aims tounite the world-leading basic and clinical institutionsacross Europe to secure the necessary critical massto address critical aspects of cardiovascular diseaseand therapy. New partnerships with pharmaceuticaland biotechnology companies will also be fosteredto encourage drug development through technologytransfer from the laboratories. By uniting andstrengthening existing programmes through EVBI,cardiovascular disease can be jointly addressed on aEuropean level.5. Combating Bacterial Pathogenesis andAntibiotic Resistance (GVG-NET)Presented by Dr. Christopher Bayliss, Universityof Leicester, Professor Alex van Belkum, ErasmusMedical Centre and Professor Tone Tonjum,University of NorwayMany bacterial pathogens are endemic withinEurope and are responsible for a significant diseaseburden which includes meningitis, gastric ulcersand gasteroenteritis. Recent years have seen anelevated incidence of new diseases such as MRSAbut also old ones such as Tuberculosis. GVG-NETaims to understand the mechanisms by whichbacterial pathogens change (‘mutate’) their geneticcode and to characterise the distribution of strainswith differences in these mutational mechanisms.This data will be essential for researchers in bothEurope and world-wide for combating antibioticresistance, pathogenesis and the spread of bacterialpathogens and may lead to new therapeutic targetsfor addressing these pathogens.6. Systems Biology to Combat MetabolicSyndrome (SBMS)Presented by Professor Roel van Driel, NetherlandsInstitute for Systems Biology and University ofAmsterdamTranslating our extensive biological knowledge intostrategies to combat diseases is disappointingly slow,due to the extreme complexity of biological systems.Systems biology offers highly promising tools toovercome the complexity hurdle. It systematicallyexploits the cycle of predictive andquantitativedata-driven modeling, to identify the most effectiveapproaches, and model-driven experimentation. Wepropose the stepwise development of a novel typeof highly focused and cost-effective internationalresearch programme aiming at understanding oneof the most threatening Western world diseases:metabolic syndrome. In this programme clinical andbiomedical research is combined with expertisein chemistry, physics, mathematics and systemengineering.Parallel Sessions10 :00 - 12 :00Session IVThe European Vascular Biology Institute (EVBI)Session VCombating Bacterial Pathogenesis and AntibioticResistance (GVG-NET)Session VISystems Biology to Combat Metabolic Syndrome(SBMS)12 :15 - 13:15Session Feedback and Closing RemarksWouter Spek, Director, EuroBioFundJohn Marks, Chief Executive, European ScienceFoundation13:30 - 15:00Lunch26 | EuroBioFund: Conference Report

Appendix III – List of ParticipantsProfessor Joaquim Alexandre-RibeiroFaculty of Medicine, Universityof Lisbon, PortugalMs. Marie José Alting vonGeusauMinistry of Health, Welfare andSport, The Hague, NetherlandsDr. Ole Herman AmburInstitute of Microbiology,Rikshospitalet Medical Centre,Oslo, NorwayMr. Philippe ArhetsDepartment of French Regionaland European Strategic Policies,Inserm, Paris, FranceProfessor Johan AuwerxInstitute of Genetics-Clinical MouseInstitute (IGBMC-ICS), Strasbourg,FranceProfessor Fernando BaqueroDepartment of Microbiology,Ramón y Cajal University Hospital,Madrid, SpainDr. Luís Filípe BastostransADVANcis – MarketingResearch and Consultancy Ltd.,Almada, PortugalDr. Christopher David BaylissDepartment of Genetics, Universityof Leicester, United KingdomDr. Edvard BeemThe Netherlands Organisation forHealth Research and Development(ZonMw), The Hague, NetherlandsDr. Monica BergemDepartment for Biology andBiomedicine, The Research Councilof Norway, Oslo, NorwayDr. Antoine BrilServier Research Institute,Suresnes, FranceProfessor Charles BuysNetherlands Organisationfor Scientific Research (NWO),The Hague, NetherlandsDr. Pat CaneHealth Protection Agency, London,United KingdomDr. Donatella CaponeDepartment of Life Sciences,National Research Council of Italy(CNR), Rome, ItalyMs. Cathy ChapelDepartment of Life Sciences,French Atomic Energy Commission(CEA), Fontenay aux roses, FranceDr. Guillaume CharpentierSud-Francilien Hospital Centre(CHSF), Corbeil Essonne, FranceDr. Catherine CluselEuropean and International Affairs,Inserm-Transfert, Paris, FranceDr. Jean Marie CohenOrganise and PromoteEpidemiological Networks(OpenRome, FP6 NoE), Paris,FranceProfessor Milton Da CostaFederation of EuropeanMicrobiological Societies (FEMS)and Department of Biochemistry,University of Coimbra, PortugalMs. Barbara DarteeFederation of EuropeanMicrobiological Societies (FEMS)Central Office, Delft, NetherlandsDr. Gerard DawsonDepartment of Psychiatry, P1vitalLtd., Headington, United KingdomMr. Marcel De LeeuwCogenics Ltd., Meylan, FranceProfessor Herminia De LencastreDepartment of Molecular Genetics,Institute of Chemical and BiologicalTechnology (ITQB), Oeiras, PortugalDr. Diego Di LorenzoLaboratory of Biotechnology,Civic Hospital of Brescia, ItalyMr. Michel DodetFrench National Institutefor Agricultural Research (INRA),Paris, FranceDr. Simona DraganVictor Babes University of Medicineand Pharmacy, Timisoara, RomaniaDr. Michael DunnThe Wellcome Trust, London,United KingdomDr. Alan EdgarF. Hoffmann-La Roche, Basel,SwitzerlandDr. Stanislav Dusko EhrlichMicrobiology and the Food Chain,French National Institute forAgricultural Research (INRA),Jouy en Josas, FranceDr. Michel FeletouDepartment of Angiology, ServierResearch Institute, Suresnes,FranceDr. Maria Joao FernandesInstitute of Experimental Biologyand Technology (IBET), Oeiras,PortugalDr. Sergio FilipeDepartment of Biology, Instituteof Chemical and BiologicalTechnology (ITQB), Oeiras, PortugalDr. Horacio FirminoPsychiatric Clinic, UniversityHospital of Coimbra, PortugalDr. Stephan FryeInstitute of Microbiology,Rikshospitalet Medical Centre,Oslo, NorwayProfessor José Mariano GagoMinister for Science, Technologyand Higher Education, Lisbon,PortugalEuroBioFund: Conference Report | 27

Appendix III – List of ParticipantsMs. Inmaculada Garcia MorenoFederal Institute for Drugs andMedical Devices (BfArM), Bonn,GermanyDr. Sarah GeorgeBristol Heart Institute, Universityof Bristol, United KingdomDr. Eli-Anne B. GjerdeDepartment of ResearchManagement, Universityof Bergen, NorwayDr. Merlin GoldmanBioscience and Healthcare,Technology Strategy Board,Swindon, United KingdomDr. Mariana Gomes de PinhoInstitute of Chemical andBiological Technology (ITQB),Oeiras, PortugalDr. Nieves Gonzalez RamonEuropean Patent Office,Delft, NetherlandsDr. Veronica GoudotMarseille-Luminy ImmunologyCentre (CIML), Marseille, FranceDr. Tobias GrimmLife Sciences Division 1, GermanResearch Foundation (DFG),Bonn, GermanyDr. Bert GroenDepartment of MedicalBiochemistry, Academic MedicalCenter, Amsterdam, NetherlandsDr. Marcus HarrisonOxford Gene Technology(Operations) Ltd, Oxford,United KingdomMs. Janna HensingResearch and Science Policy,Ministry of Education, Culture andScience, The Hague, NetherlandsProfessor Stefan HohmannDepartment of Cell and MolecularBiology, Göteborg University,SwedenDr. Doris HöscheleFederal Institute for Drugs andMedical Devices (BfArM), Bonn,GermanyDr. Thomas HudsonOntario Institute for CancerResearch, Toronto, CanadaDr. Stephane HuetDepartment of Biology,GlaxoSmithKline Laboratory, LesUlis, FranceDr. José Luis JorcanoChief Executive, Genoma España,Madrid, SpainDr. Sid KatugampolaBiomarker and TranslationalBiology, Pfizer UK, Sandwich,United KingdomDr. Francois KépèsGenopole, Évry, FranceDr. Hector KeunDivision of Surgery, Oncology,Reproductive Biology andAnaesthetics, Imperial College,London, United KingdomProfessor Jos KleinjansDepartment of Toxicology andHealth Risk Analysis, MaastrichtUniversity, NetherlandsProfessor Gitte Moos KnudsenNeurobiology Research Unit,Rigshospitalet, Copenhagen,DenmarkDr. Patrik KolarGenomics and Systems Biology,DG Research, EuropeanCommission, Brussels, BelgiumDr. Jochen KönigGenedata AG, Basel, SwitzerlandDr. Hannele LahtinenBiosciences and EnvironmentResearch Unit, Academyof Finland, Helsinki, FinlandProfessor Adriaan AnthoniusLammertsmaDepartment of Nuclear Medicine& PET Research, VU UniversityMedical Centre, Amsterdam,NetherlandsProfessor Michel Paul LamureDepartment of Computer Science,University of Lyon, Villeurbanne,FranceDr. Frank LaplaceMolecular Life Sciences,Federal Ministry of Educationand Research, Berlin, GermanyProfessor Marc LaruelleGlaxoSmithKline,Clinical Imaging Centre,Imperial College London,United KingdomDr. Maria Joao LeaoGulbenkian Science Institute(IGC), Oeiras, PortugalProfessor Xavier LeverveHuman Nutrition and FoodSecurity, French National Institutefor Agricultural Research (INRA),Paris, FranceMs. Michèle LonguetDepartment of Health, Ministryof Higher Education andResearch, Paris, FranceDr. Anna Kristina LonnrothInfectious Diseases, DG Research,European Commission, Brussels,BelgiumDr. Maria de Fátima LopesInstitute of Experimental Biologyand Technology (IBET), Oeiras,Portugal28 | EuroBioFund: Conference Report

Dr. Claus LundegaardCentre for Biological SequenceAnalysis, The Technical Universityof Denmark (DTU), Lyngby,DenmarkDr. Astrid LunkesLife, Earth and EnvironmentalSciences, European ScienceFoundation, Strasbourg, FranceDr. John MarksChief Executive, European ScienceFoundation, Strasbourg, FranceDr. Giuseppe MartiniDepartment of Life Sciences,National Research Council of Italy(CNR), Rome, ItalyDr. Luis MarquesHPL Ltd., Antanhol, PortugalProfessor Carlos Martínez-A.President, Spanish NationalResearch Council (CSIC), Madrid,SpainDr. Paulo Emanuel MarujoDepartment of Microbiology,Institute of Chemical and BiologicalTechnology (ITQB), Oeiras, PortugalDr. Simone MerguiDepartment of Life Sciences/Institute of Biomedical Imaging,French Atomic Energy Commission(CEA), Orsay, FranceMr. Maxime MontagnerCommunity Research andDevelopment Information Service(CORDIS), Brussels, BelgiumDr. William NewellInforSense Ltd., London,United KingdomDr. Sirpa NuotioAcademy of Finland, Helsinki,FinlandProfessor David NuttPsychopharmacology Unit,University of Bristol,United KingdomProfessor Jes OlesenEuropean Brain Council, Brussels,Belgium and Department ofNeurology, Glostrup Hospital,University of Copenhagen,DenmarkDr. Mark PalmerInternational Policy, MedicalResearch Council, London, UnitedKingdomDr. Gabriela PastoriExternal Science Relations,Biotechnology and BiologicalSciences Research Council(BBSRC), Swindon, UnitedKingdomProfessor Jeremy PearsonBritish Heart Foundation, London,United KingdomMs. Louise PerbalScience Policy, Ministry ofEducation, Culture and Science,The Hague, NetherlandsDr. Sandra Maria Pinto MarquesGenomics and Systems Biology,DG Research, EuropeanCommission, Brussels, BelgiumMr. Rene ReijndersResearch Management, MaastrichtUniversity, Maastricht, NetherlandsDr. Geneviève Renauld-MongénieDiscovery, Sanofi Pasteur, Marcyl’Étoile, FranceDr. Catarina ResendeFoundation for Science andTechnology (FCT), Lisbon, PortugalDr. Stéphanie RingeissenSafety Research Department –In Silico Group, L’Oréal AdvancedResearch, Aulnay sous bois cedex,FranceDr. Erwin L. RoggenPharma Protein Development,Novozymes AS, Bagsvaerd,DenmarkProfessor Jean Luis RometteViral Replicases, Laboratory forthe Architecture and Function ofBiological Macromolecules (AFMB/CNRS/University of Aix-Marseilles),FranceMs. Tatjana RudezNewspaper Jutarnji List, Zagreb,CroatiaDr. Bart SangsterFormerly, Safety and EnvironmentalAssurance, Unilever, London,United KingdomDr. Susana SantosAmBioDiv (Private SectorConsultancy), Lisbon, PortugalDr. Beatrice SchaackBioPuces Laboratory, FrenchAtomic Energy Commission (CEA),Grenoble, FranceProfessor Michael SchwarzDepartment of Toxicology,University of Tuebingen, GermanyDr. Richard SeabrookThe Wellcome Trust, London,United KingdomProfessor João SentieiroPresident, Portuguese Foundationfor Science and Technology (FCT),Lisbon, PortugalMs. Marjanne SlotSpects Special Projects, Leiden,NetherlandsProfessor Henrique Sobraldo RosarioInstitute of Molecular Medicine,University of Lisbon, PortugalDr. Oda StoevesandtThe Babraham Institute,Cambridge, United KingdomEuroBioFund: Conference Report | 29

Appendix III – List of ParticipantsDr. Peter SuedbeckProject Management Agencypartof the German AerospaceCenter (PT-DLR), Bonn, GermanyDr. Johannes TauscherTranslational Imaging Group,Eli Lilly and Co., Indianapolis,United StatesDr. Michael TaussigThe Babraham Institute,Cambridge, United KingdomProfessor Alain TedguiCardiovascular Research Center,Hospital Lariboisière, Inserm,Paris, FranceDr. Jochen TheisF. Hoffmann La Roche Ltd.,Basel, SwitzerlandProfessor Tone TonjumInstitute of Microbiology,University of Oslo, NorwayProfessor Alex van BelkumErasmus Medical Centre,Rotterdam, NetherlandsDr. Wilma van DonselaarNetherlands Genomics Initiative,The Hague, NetherlandsProfessor Roel van DrielNetherlands Institute for SystemsBiology (NISB) and Universityof Amsterdam, Amsterdam,NetherlandsDr. Matthias von WitschProject Management Agencypartof the German AerospaceCenter (PT-DLR), Bonn, GermanyDr. Tore VulpiusMSC Aps Ltd., Skovlunde,DenmarkDr. Christiane Walch-SolimenaMax Planck Society, Munich,GermanyDr. Dieter WeichartManchester Centre for IntegratedSystems Biology (MCISB),University of Manchester, UnitedKingdomDr. Jerome WeinbachInternational Development,Inserm-Transfert, Paris, FranceDr. Carl WestmorelandSafety and EnvironmentalAssurance Centre, Unilever,London, United KingdomProfessor Jürgen WolfrumInstitute of Physical Chemistry,University of Heidelberg,Heidelberg, GermanyProfessor ChrysanthosZamboulisNational Hellenic ResearchFoundation (NHRF), Thessalonika,GreeceDr. Luc van DyckInitiative for Science in Europe(ISE) and European Life SciencesForum (ELSF), Heidelberg,GermanyDr. Sheila VidalGulbenkian Science Institute(IGC) – Calouste GulbenkianFoundation, Oeiras, Portugal30 | EuroBioFund: Conference Report

Published by the European Science FoundationApril 2008Suggested citation:EuroBioFund: EuroBioForumConnecting Life Sciences,Lisbon, Portugal, 5-7 December 2007. Conference report.ESF, Strasbourg, April 2008This report incorporates opinions expressed at the conference.They do not necessarily represent the views of the EuropeanScience Foundation or its Member Organisations.Printing: IREG StrasbourgReport Editing: Fiona KernanRapporteur Brokerage Sessions: Sandra Pinto-Marques,Catarina ResendeISBN: 2-912049-79-2

1 quai Lezay-Marnésia | BP 9001567080 Strasbourg cedex | FranceTel: +33 (0)3 88 76 71 00 | Fax: +33 (0)3 88 37 05 32www.esf.orgPrint run: 500– April 2008

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