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Home > Research teams > Chromatin and Regulation of bacterial Pathogenesis > Thesis/internship proposals

Thesis/internships

Thesis and Master’s degree internships can be proposed in the team, please take contact with the team members. Specific current projects are described below.

Chromosome topology as a global regulator of gene expression in bacteria : multi-scale analysis and computational modeling

Supervisor : Sam Meyer
Co-supervisor : Sylvie Reverchon

Field : Computational biology

Thesis project and shorter versions available for internships

The student will explore and characterize the multiscale relation between the physical organization of the bacterial chromosome and the regulation of gene expression. In contrast to usual regulation mechanisms involving highly specific transcription factors binding at a gene’s promoter, DNA topology influences gene expression in a global, non-specific manner. In bacteria, modifying the topology allows for a rapid re-programming of the expression program along the whole chromosome, for instance in response to an external stress [1]. Accordingly, accumulating data show that gene expression is organized spatially on the chromosome following topological and architectural domains [2], and depends for instance on the presence and orientation of neighbor genes [3]. These features are evolutionarily conserved and cannot be explained by current regulation models.
This computational biology study will be based on an analysis of recent high-throughput RNA-sequencing data obtained in the team on the pathogenic bacteria Dickeya dadantii as well as published data on other organisms. Depending on the student’s background, skills and preferences, it may either be centered (1) on statistical data analyses, in order to test how the location of genes on the chromosome affects their expression, or (2) on the development of mathematical/biophysical models of the underlying molecular mechanisms (stochastic or thermodynamic models of gene expression). Since the explored regulation mechanism is based on the fundamental physical properties of the DNA double helix, it probably constitutes an important ancestral and widespread mode of regulation currently underestimated; the study may thus have an important fundamental impact by relating the chromosome’s physical features to its biological function. It may also be relevant to a broad range of organisms and will be conducted in this perspective.
Relevant skills : programming, RNA-sequencing data, mathematical/biophysical modeling, statistics.

References:
[1] Travers, A. and Muskhelishvili, G. (2005). DNA supercoiling - a global transcriptional regulator for enterobacterial growth?, Nat Rev Microbiol
3 : 157-169.
[2] Jiang, X.; Sobetzko, P.; Nasser, W.; Reverchon, S. and Muskhelishvili, G. (2015). Chromosomal “Stress-Response” Domains Govern the
Spatiotemporal Expression of the Bacterial Virulence Program, mBio 6.
[3] Meyer, S. and Beslon, G. (2014). Torsion-Mediated Interaction between Adjacent Genes, PLoS CB 10 : e1003785