Reference : UPR4301-LAELEG-011
Workplace : ORLEANS
Date of publication : Tuesday, September 20, 2022
Scientific Responsible name : Marc Boudvillain
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 January 2023
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
In the context of a collaborative project funded by the French ANR agency, the recruited PhD student will deploy RNA biology/biochemistry approaches to identify and characterize, at genome scale, the physiological RNA substrates of the transcription termination factor Rho from Mycobacterium tuberculosis (Mtb). A complementary part of the work will involve NMR analysis of the role of an intrinsically disordered domain of Mtb Rho in the specific recognition of these RNA substrates.
Rho-dependent transcription termination is a bacteria-specific mechanism, which makes it a particularly interesting therapeutic target. Rho is essential in Mtb where it is likely to modulate the expression of many genes. The comprehensive identification of Mtb Rho substrates and a better understanding of the mechanisms of mycobacterial Rho-dependent termination are important steps for the development of new, specific antibiotics.
A large part of the work will revolve around a new proprietary biochemistry approach, Helicase-SELEX, which was developed specifically to study enzymes with helicase activity such as Rho.
The PhD will be undertaken in the 'RNA Remodeling' team of the Centre de Biophysique Moléculaire (CBM) on the Orléans campus of CNRS. The campus is close to the University of Orléans in the beautiful Loire valley city of Orleans, ~1h from Paris by train. CBM is an interdisciplinary laboratory that develops research at the interface between biology, chemistry and physics.
Constraints and risks
- The work will involve handling of fragile enzymes and RNA samples, some radio-labeled with 32P. Great meticulousness and strict compliance with health & safety rules will be mandatory.
- The multidisciplinary nature of the project will require good technical and scientific adaptability.
- Occasional trips to the high-field NMR platform of Gif-sur-Yvette (south of Paris) may be necessary.
Applications should include a CV, a cover letter, and a letter of recommendation and should be submitted only via the CNRS recruitment system.
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