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organisation - the Instituto Gulbenkian de Ciência

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BACTERIAL<br />

SIGNALLING<br />

Karina B. Xavier Principal Investigator<br />

PhD in Biochemistry, Universida<strong>de</strong> Nova <strong>de</strong> Lisboa, 1999<br />

Research Scientist, Princeton University, USA<br />

Principal Investigator at <strong>the</strong> IGC since 2006<br />

Bacteria use small molecules called autoinducers to communicate with one ano<strong>the</strong>r<br />

by a process called quorum sensing. This process enables bacteria to regulate<br />

behaviours which are only productive when many bacteria act as a group,<br />

similarly to multi-cellular organisms. Behaviours regulated by quorum sensing<br />

are often crucial for successful bacterial-host relationships whe<strong>the</strong>r symbiotic<br />

or pathogenic. We use an integrative approach, from molecules to circuits, to<br />

un<strong>de</strong>rstand <strong>the</strong> role of quorum sensing in bacterial behaviours. Our research<br />

involves elucidation of <strong>the</strong> molecules used as signals, <strong>the</strong> network components<br />

involved in <strong>de</strong>tecting <strong>the</strong> signals and processing information insi<strong>de</strong> individual<br />

cells, and characterisation of <strong>the</strong> behaviour of <strong>the</strong> bacterial community in multispecies<br />

bacterial consortia. We aim to <strong>de</strong>termine <strong>the</strong> role of cell-cell communication<br />

in multispecies consortia such as <strong>the</strong> microbiota of <strong>the</strong> mammalian gut, a<br />

community of great importance to human health.<br />

INTER-SPECIES CELL-CELL SIGNALLING:<br />

ITS ROLE IN BACTERIA CONSORTIA<br />

This project will start in 2012.<br />

GROUP MEMBERS<br />

Jessica Thompson (Post-doc, started in April)<br />

Pol Nadal (Post-Doc, started in February)<br />

Catarina S. Pereira (PhD stu<strong>de</strong>nt)<br />

Rita Valente (PhD stu<strong>de</strong>nt)<br />

Paulo J. Correia (Trainee)<br />

COLLABORATORS<br />

Isabel Gordo (IGC Portugal)<br />

Jocelyne Demengeot (IGC, Portugal)<br />

Stephan Miller (Swarthmore College, USA)<br />

Rita Ventura (ITQB, Portugal)<br />

FUNDING<br />

Howard Hughes Medical Institute (HHMI), USA<br />

Fundação para a Ciência e a Tecnologia (FCT), Portugal<br />

PUBLIC ENGAGEMENT IN SCIENCE<br />

TV interview for science & technology series<br />

In this project we will use an integrated approach towards <strong>the</strong> characterisation<br />

of <strong>the</strong> molecular mechanisms involved in inter-species cell-cell communication<br />

and its role in bacterial-host interactions. Our approach is composed of three<br />

specific aims:<br />

1. Characterisation of <strong>the</strong> molecular mechanisms involved in <strong>the</strong> regulation of<br />

sensing and response to AI-2, <strong>the</strong> best studied interspecies signal, in <strong>the</strong><br />

mo<strong>de</strong>l bacteria Escherichia coli;<br />

2. I<strong>de</strong>ntification of novel inter-species signals. There is substantial evi<strong>de</strong>nce<br />

of additional signals mediating interspecies quorum sensing in<br />

γ-proteobacteria but <strong>the</strong> molecules remain uni<strong>de</strong>ntified;<br />

3. Study of AI-2 signalling directly in vivo. We propose to extend our approaches<br />

to study interspecies interactions directly in <strong>the</strong> gut of mice.<br />

This work can lead to <strong>the</strong> rational <strong>de</strong>velopment of novel <strong>the</strong>rapies that specifically<br />

target inter-species quorum sensing to control complex bacterial communities.<br />

INHIBITION OF BACTERIAL PLANT VIRULENCE BY INTERFERENCE<br />

WITH INTERSPECIES CELL-CELL COMMUNICATION.<br />

In Erwinia carotovora virulence is regulated by non-species specific signal that<br />

foster interspecies communication. In this project we aim to i<strong>de</strong>ntify receptor<br />

protein(s) and <strong>the</strong> molecular components of signal transduction involved in recognition<br />

and response to interspecies signals. We will study how <strong>the</strong>se mechanisms<br />

influence gene expression in Erwinia carotovora to <strong>de</strong>termine its impact<br />

in virulence using <strong>the</strong> potato tuber infectious assay. These bacteria can persist<br />

in <strong>the</strong> Drosophila gut and induce inflammation. We are studying <strong>the</strong> effect of<br />

mutants impaired in interspecies communication in Erwinia-Drosophila interactions<br />

in <strong>the</strong> presence or absence of o<strong>the</strong>r bacterial species. We hypo<strong>the</strong>sise that<br />

Erwinia uses Drosophila as a vector for infection and that interspecies communication<br />

has an important role in this process.<br />

We have performed a genetic screen for mutants impaired in regulation of virulence<br />

factors mediated by interspecies signals. We are analysing <strong>the</strong>se mutants<br />

to i<strong>de</strong>ntify a new signal involved in interspecies communication and also to<br />

<strong>de</strong>termine <strong>the</strong> impact of <strong>the</strong>se mutants in <strong>the</strong> production of virulence factors<br />

involved in <strong>the</strong> pathogenesis of Erwinia towards fruits and legumes but also<br />

during <strong>the</strong> interaction between Erwinia and Drosophila.<br />

COLONIES OF XENORHABDUS SPP. A PROTEOBACTERIA.<br />

This bacteria un<strong>de</strong>rgoes a complex life cycle that involves a symbiotic stage, in<br />

which <strong>the</strong> bacteria are carried in <strong>the</strong> gut of <strong>the</strong> nemato<strong>de</strong>s, and a pathogenic<br />

stage, in which susceptible insect prey are killed by <strong>the</strong> combined action of <strong>the</strong><br />

nemato<strong>de</strong> and <strong>the</strong> bacteria.<br />

IGC ANNUAL REPORT ‘11<br />

RESEARCH GROUPS<br />

67

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