PhD PROPOSAL FOR THE PASTEUR-PARIS UNIVERSITY INTERNATIONAL PROGRAM

 

Deadline for full application: December 15th, 2013

Interviews: March, 2014

Start of the Ph.D.: October 1st, 2014

 

 

Department: Genomes and Genetics

Title of the PhD project: Understanding the organization of the 2 chromosomes genome of Vibrio cholerae

Name of the lab: Bacterial Genome Plasticity

Head of the lab: Didier Mazel

PhD advisor: Didier Mazel and Marie-Eve Val

Email address: mazel@pasteur.fr

Web site address of the lab:  http://openwetware.org/wiki/Mazel

 

Doctoral school affiliation and University:

 

Complexité du Vivant / Université Paris 6

 

 

Presentation of the laboratory and its research topics:

 

We study the mechanisms responsible for bacterial genome organization and variability, with a special interest for those involved in exogenous gene acquisition – the horizontal gene transfer. Our model system is the integron, a natural genetic engineering system involved in the development and dissemination of antibiotic resistance genes among Gram-negative species.

We are also investigating other factors playing a role in the plasticity of the Vibrio species genomes, which are all constituted of two circular chromosomes with distinct dynamic characteristics. We are studying the genetic characteristics brought by this 2 chromosome organization.

 

 

 

 

 

Description of the project:

 

 

Until recently, genome fragmentation into different chromosomes was considered to be an exclusive eukaryote property, nevertheless, an increasing number of observations show that many bacterial species, such as all Vibrio species, also share this characteristic (Dryselius et al 2007). The selective advantages, and constraints, of this division into two replicons are still elusive and mostly unknown. Vibrio species are characterized by short generation times (eg V. natriegens has a generation time of 9 mn). Comparison of Vibrio genomes has shown that in the course of their evolution, numerous and frequent genetic exchanges have occurred intra- rather than inter-chromosomally. In order to better understand the selective advantage brought by this 2-chromosomes organization, we have created several strains with remodeled genomes, from a strain with a single chromosome made by directed fusion of the two chromosomes to a strain with 2 chromosomes of equal size (Val et al 2012). We have undertaken the in vivo exploration of the spatial proximity of the 2 chromosomes and the determination of their physical architecture through three different approaches. We have now identified several proteins which likely play a role in chromosome structuration and are likely important for proper segregation upon cell division (Val et al, submiited).

The project we propose is the characterization of these proteins, the role they play in the V. cholerae cell cycle and their regulation. We have also identified a number of DNA motifs with a specific distribution, which can also play a role in chromosome structuration and behavior, that we plan to study to determine the kind of role they play in these chromosomes. The approaches that will be used to reach these goals go from next generation sequencing approaches, transcription analysis, to bacterial genetics and microscopy.  

 

References:

 

Dryselius R, Kurokawa K, Iida T. Vibrionaceae, a versatile bacterial family with evolutionarily conserved variability. Res Microbiol. (2007) 158(6):479-86.

 

Val M-E, Skovgaard O, Ducos-Galand M., Bland M.J. and Mazel D. Genome engineering in Vibrio cholerae: A feasible approach to address biological issues. PLoS Genetics (2012) 8(1): e1002472.

 

Val M-E, Kennedy S P, Barbe V, Bouchier C, Ducos-Galand M, Skovgaard O, and Mazel D. Fuse or Die : How to survive the loss of Dam in Vibrio cholerae. Submitted

 

Keywords: Vibrio cholerae, virulence, chromosome, recombination, replication, NGS.

 

Expected profile of the candidate (optional):

 

Contact:          Didier MAZEL, mazel@pasteur.fr

 

Mis à jour le 16/09/2013