Date : 11/03/10

Laboratory

Epigenomics Project / ISC-PIF CNRS UPS3201
Genopole campus 1 - Genavenir
65 rue Henri Desbruères 91030 EVRY cedex
Director : François Képès

PhD Supervisor

François KEPES
email : Cet e-mail est protégé contre les robots collecteurs de mails, votre navigateur doit accepter le Javascript pour le voir
phone : +33 169474431

Subjects / Tools-Methodologies

1 : Integrative Biology/Metabolism and DNA replication
2 : Chromosome structure and evolution/Systems and Synthetic Biology
3 : Bioinformatics/Complex Systems

Summary of lab's interests

GIP Genopole hosts an Institute of Complex Studies dedicated to modelling and simulation of complex biological processes in the post-genomic era, called the Epigenomics Project, and headed by F. Képès. The Epigenomics Project is a CNRS Unit. This lab includes computer scientists, physicists and biologists / bioinformaticists. It has a long-standing tradition of multidisciplinary projects. www.epigenomique.genopole.fr/~kepes The ISC-PIF (Institut des Systèmes Complexes, Paris Ile-de-France) is a multidisciplinary research and training center promoting the development of French, European and international strategic projects on complex adaptive systems. It is headed by René Doursat.

http://iscpif.fr/tiki-index.php?page=home

Summary of project

Global and multiscale modeling of cell function must include an integration of the cellís different functional components. This requires understanding the principles underlying the overall coordination of the genetic networks associated with these functions.

A promising and widely used approach consists in studying the functional organization of the chromosome in cellular space. The aim is to identify the mechanisms that are responsible for the coordination of the spatiotemporal expression of co-functional genes - see ref [1] and references therein. In this context, recent genomic and transcriptomic analysis suggests that a specific functional organization of the chromosome implies a specific organization of the genome [2].

Based on an observed tendency of co-functional genes to be located in close proximity along the DNA (termed "synteny"), we have built a novel network of proximity relationships - the "closome" - in which all biological functions are represented. Preliminary topological studies have already identified many well-known functional modules but also unconventional links for which experimental evidence is only recent, in particular the existence of genetic links between enzymes that are involved in carbon metabolism and enzymes that are involved in the replication machinery [3]. Objectives of the thesis are the following: i) investigating the biological meaning and the biological consequences of the closome; ii) characterizing the principles (or at least the phenomena) underlying the functional organization of chromosomes/genomes; and iii) studying the mechanisms responsible for a proper coordination of gene expression at the cellular level.

To achieve these objectives, various methods/tools will be used:

** Further topological analysis of the network, either by using existing tools or by developing new ones (methods from graph theory, statistical approaches, visualization graphs, etc.)
** Semantic/functional study of the network using data mining, literature/text mining
** Comparison with known biological networks
** Phylogeny (comparative genomics)
** Investigation of the closome organization in specific organisms (specificity of the functional organization of the chromosome) In vivo experiments can be envisaged. The aim will be to validate, or not, the predictions made by the analysis of the network(s).

Candidates must have an interest and competence in both network analysis and biology. Advanced skills in computing tools are essential. Candidates with experience in ìwetî biology are strongly encouraged to apply.

Supervisors: François Képès, Laurent Jannière, René Doursat Scientific
staff: René Doursat (computer science and complex systems), Laurent Jannière (microbiology), Ivan Junier (physics), François Képès (systems biology), Jean-Baptiste Rouquier (theoretical computer science)

[1] Junier, Martin, Képès, Spatial and topological organization of DNA chains induced by gene co-localization. PLoS Comput Biol (2010) vol. 6 (2) pp. e1000678
[2] K…P»S, PERIODIC EPI-ORGANIZATION OF THE YEAST GENOME REVEALED BY THE DISTRIBUTION OF PROMOTER SITES, J MOL BIOL (2003) VOL. 329 (5) PP. 859-65; K…P»S, PERIODIC TRANSCRIPTIONAL ORGANIZATION OF THE E.COLI GENOME, J MOL BIOL (2004) VOL. 340 (5) PP. 957-64.
[3] Jannière et al. Genetic evidence for a link between glycolysis and DNA replication. PLoS ONE (2007) vol. 2 (5) pp. e447