Date : 22/03/2011

Laboratory/
Bacterial Cytoskeleton and Bacterial Cell Morphogenesis Lab
UMR 1319 - Micalis INRA AgroParisTech
INRA Domaine de Vilvert
78352 Jouy en Josas cedex
Website : http://www.jouy.inra.fr/jouy_eng/
Main discipline : Systems Biology
Lab director : Stéphane Aimerich

PhD Supervisor
Rut CARBALLIDO LOPEZ
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : +33 1 34.65.25.34

Subjects
1.: Bacterial cell wall, bacterial cell morphogenesis, peptidoglycan
2.: Systems Biology
3.: Genetic modules, dynamic data, global control mechanisms of complex biological functions

Tools and methodologies
1.: Transcriptomics -Tiling Array, Live Cell Array (LCA)
2.: Modeling, Mathematics, Statistics
3.: Genetics, Molecular Biology, Cell Biology, Biophysics, Microscopy

Summary of lab's interests

The general goal of the 'Bacterial Cytoskeleton and Bacteriall Cell Morphogenesis Lab' (host lab 1) is to understand how the highly dynamic bacterial cytoskeleton generates the extraordinary spatial and temporal precision characteristic of most cellular processes, in particular morphogenesis of the bacterial cell wall (the most prominent target for antibiotics). We aim: 1) to determine the role(s) of the bacterial cytoskeleton in different cellular processes such as cell shape determination, cell division, DNA segregation, polarity and secretion; 2) to identify the molecular mechanisms involved in these processes and 3) to elucidate the factors controlling bacterial cell wall morphogenesis. To these ends, we use a combination of genetic, genomic, microscopic, biochemical, physicochemical, transcriptomics and mathematical modelling approaches at a number of levels. Emphasis is put in a pluri- and interdisciplinary approach to address complex biological functions in the mo del Gram-positive bacterium Bacillus subtilis. The 'Biology Systems Lab' (host lab 2) develops mathematical methods and informatics tools to understand the role of regulation networks in live cells. Beyond the expertise in the tools and methods currently used, mostly from the automatics (non-linear or distributed), optimisation and informatics fields, a specificity of the lab is its involvement in interdisciplinary projects. Over the last few years, the lab has developed an important expertise in the model bacterium Bacillus subitlis, in particular in its regulation networks (from metabolic pathways to growth rate management or stress response). Progress on the mathematical understanding of B. subtilis regulation networks have also recently broaden the lab's interest to the development of methods of synthetic biology for biotechnology purposes (European project BaSyntech)

Summary of project

The cell wall (CW) is the main determinant of cell shape in bacteria, and the target of many antibiotics. Although the chemical composition of the CW is well known, the factors controlling CW synthesis and structure remain largely unknown. After a first integration of current knowledge about CW synthesis, statistical and bioinformatics approaches will be used to reveal meaningful sets of gene modules involved in the control of CW biogenesis in Bacillus subtilis. Analysis of the activity patterns of the different pathways will pinpoint mechanistic details involved in the synthesis and maturation of the individual CW polymers and of both the sidewall (elongation) and the crosswall (septation). The biological significance of the models will be validated and refined by genetic, biochemical, transcriptomics and Life Cell Array (LCA) approaches.

Interdisciplinarity of the project

This a highly interdisciplinary Systems Biology project. Current methods to analyse the available genomic and post-genomic datasets are not yet optimal. Thus, it seems necessary to us to reformulate complex biological questions, such as the control of bacterial cell wall synthesis, and use a systems modelling approach. To this end, the project requires the joint effort of two labs from very different disciplines: one of biologists and one of mathematicians/modellers (co-hosts and co-supervisors of the PhD). Our respective regular graduate schools are therefore either pure 'Live Sciences' or 'Mathematics' and thus not suitable for this project. We need a multidisciplinary graduate school at the crossroad of several disciplines; where students master the problems facing biologists and share the language of computer scientists and mathematicians. Finally, the project has an important international component. The host labs conduct several international collaborations direct ly linked to this project. The PhD student will interact with foreigner partners and do stays in one or several of the collaborator labs. In summary, we need a graduate school with an INTERNATIONAL INTERDISCIPLINARY PhD program. Fdv 'recruits outstanding students into an interactive PhD program that gets students to think critically, work collaboratively, learn, and work outside of disciplinary boundaries' and thus we believe that it is the ideal graduate school for this project. We are seeking for a candidate holding either 1) a degree in multidisciplinary Biosciences engineering OR 2) a degree in Live Sciences + MsC or equivalent in Bioinformatics and/or Modelisation Strong scientific and technical training in Applied Mathematics, (Bio)informatics, Live Sciences, Chemistry and Physics as well as project and laboratory experience in Molecular Biology, Cell Biology, Microbiology, Biophysics or similar are required. 'Transversal' skills in organising and managing projects and/or acquisition, retrieval and analysis of large data sets will be favorable.

Available funding for this project

HFSP Young Investigator Grant (PI) , ANR Jeune Chercheur (PI), European - BaSyntech (partner)