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Internship (BioInfo) - Host gene expression during Listeria infection

Duration : 6 months, starting January 2018
Location : IBENS, teams Computational Bioimaging and Bioinformatics and Bacterial Infection and RNA Destiny
Contacts : Mathieu Bahin, Auguste Genovesio and Alice Lebreton

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Internship purpose – Integrating all layers of host gene expression regulation during infection by an intracellular pathogen.

Project

The project consists in a bioinformatic analysis of a large sequencing dataset produced in house. The candidate will work at the frontier between the Bacterial Infection and RNA Destiny team led by Alice Lebreton and the Computational Bioimaging and Bioinformatics team led by Auguste Genovesio at the Biology Institute of École normale supérieure.

Datasets obtained through different sequencing techniques (RNA-Seq with Illumina and Nanopore Minion, nascent RNA sequencing and Ribosome Profiling) were obtained in parallel from human intestinal cells infected over time by Listeria monocytogenes. Those datasets are now fully available for analysis.

The goal of this internship project will be to highlight global and gene-specific regulations occurring at various stages of the gene expression (transcription, splicing, stability and translation). The first steps of the statistical analyses have been performed and should be continued through this internship. The project will now consist in combining those different kinds of sequencing data, in order to cluster groups of genes sharing common regulatory patterns over time. These groups could then be statistically tested as a whole as acting or not on known molecular pathways. This analysis will take advantage of Python scripts along with software tools such as Pathway Studio or specialized R packages. The final aim is to fully grasp regulatory networks affected by the infection from nascent transcripts to protein production.

This internship can possibly lead to a PhD project with broader perspectives on the understanding of the multiple layers of host gene expression during infection.

Profile
  • Student in Master’s or engineer curriculum
  • Comfortable with Linux environment
  • Programming skills (especially Python)
  • Knowledge in molecular biology and genomics

 

Biological context

The food-borne pathogen Listeria monocytogenes is the etiological agent of listeriosis, an opportunistic disease with serious outcomes in the elderly, in immunocompromised individuals, foetuses or new-borns (reviewed in Lebreton et al. 2016). This bacterium can enter and proliferate in the cytosol of most human cell types and spread to neighbouring cells, using an arsenal of virulence factors that target diverse cellular components and subsequently hijack various host cell functions (reviewed in Cossart and Lebreton 2014).

Invasion and proliferation of Listeria monocytogenes in human cells trigger drastic changes in gene expression. The combination of these bacterial and cellular activities conditions bacterial physiology, cell survival, tissue immune response, and finally shapes the pathological outcome of the infection. The team Bacterial Infection and RNA Destiny explores the consequences of the infection on eukaryotic mRNA stability and translation, its molecular mechanisms, and its physio-pathological consequences.