Doctorat en biologie moléculaire (M/F)

Job Description

Thesis Subject

Investigating the post-transcriptional function of two-component systems in Escherichia coli
Regulation of bacterial gene expression is crucial for the ability of these microorganisms to adapt to and colonize very diverse environments. Central to this process are the two-component systems (TCSs), transduction modules commonly composed of a histidine kinase (HK) receptor that, upon sensing specific external stimuli, phosphorylates a cognate response regulator (RR) protein. In bacteria, the majority of RRs act as DNA-binding transcription factors that, upon phosphorylation, bind to promoter regions to modulate gene expression. Recognition of the DNA sequence by RRs mostly relies on the highly conserved helix-turn-helix (HTH) motif which is present in the three domains of life. For instance, among the 30 TCSs that have been identified in Escherichia coli (E. coli), approximately 25 RRs possess an HTH domain with known DNA binding activity. Importantly, various mechanisms act synergistically to ensure proper expression and activity of TCSs. Besides their transcriptional control by specific transcription factors, we and others have shown that TCSs can be regulated at the post-transcriptional level by small regulatory RNA (sRNA) and small proteins called modulators which act by influencing the stability and translation of mRNA or by impacting the efficiency of the signal transduction between the HK and the RR, respectively. Connections between these different mechanisms and TCSs exist and constitute complex mixed regulatory circuit which, altogether, contribute to bacteria survival and adaptation.
Strikingly, recent studies have uncovered unexpected findings with potential implication for the biology of TCSs: a significant fraction of HTH-containing proteins is able to interact with RNA in distant bacteria such as E. coli, B. subtilis, S. pyogenes or S. aureus as well as in budding yeast and in human. Indeed, by analyzing the global RBPome (i.e., the set of all proteins interacting with RNA), researchers have detected various transcription regulators, including RRs in E. coli, as possible new RNA-binding proteins. These observations suggest a possible novel function of these proteins in post-transcriptional regulation. However, neither the role of these interactions nor the nature of the RNAs interacting with the RRs are currently known. Using molecular biology, biochemistry and RNA sequencing-based approaches, the goal will be to validate the RNA-binding activity of TFs and to characterize the function and biochemical properties of TF-RNA interactions in E. coli. These experiments will provide a first approach to then elucidate the molecular mechanism and the role of RNA-protein interactions in gene regulation and bacterial physiology. Together, these experiments will bring a completely new angle to the study of the TCS regulation.

Your Work Environment

This project will be carried out within the "Control of Gene Expression by RNAs" team, one of the 5 teams in the "Microbial Gene Expression" department, located at the Institut de Biologie Physico-Chimique (IBPC) in the 5th arrondissement of Paris.
The thesis director will be Maude Guillier (HDR), and the project leader will be Drice Challal, Maître de Conférences (Associate Professor) at Université Paris Cité.

Constraints and risks

Risks related to the use of chemical products (including CMR—carcinogenic, mutagenic, or toxic to reproduction) and the use of radioactivity.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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