Description du sujet de thèse

This project explores how modifications to ribosomal RNA (rRNA) influence bacterial resistance to antibiotics, with the goal of targeting these modified RNAs using antimicrobial compounds. We combine approaches from genetics, biology, and chemistry to: 1. Assess the impact of rRNA modifications on antibiotic response; 2. Study a specific modification introduced by a recently identified bacterial enzyme; 3. Develop molecules that target modified rRNA as a novel antimicrobial strategy.

Publications :
Babosan A, Fruchard L, Krin E, Carvalho A, Mazel D, Baharoglu Z. Non-essential tRNA and rRNA modifications impact the bacterial response to sub-MIC antibiotic stress. microLife. 2022. doi: 10.1093/femsml/uqac019.
Fruchard L, Babosan A, Carvalho A, Lang M, Li B, Duchateau M, et al. Aminoglycoside tolerance in Vibrio cholerae engages translational reprogramming associated to queuosine tRNA modification. eLife. 2025. doi: 10.7554/eLife.96317.
Kovachka S, Panosetti M, Grimaldi B, Azoulay S, Di Giorgio A, Duca M. Small molecule approaches to targeting RNA. Nat Rev Chem. 2024;8(2):120-35. Epub 20240126. doi: 10.1038/s41570-023-00569-9.
Maucort C, Bonnet M, Ortuno JC, Tucker G, Quissac E, Verreault M, et al. Synthesis of Bleomycin-Inspired RNA Ligands Targeting the Biogenesis of Oncogenic miRNAs. J Med Chem. 2023;66(15):10639-57. doi: 10.1021/acs.jmedchem.3c00797.

Activities:
Construction of strains and plasmids
Phenotypic stress survival tests
Extraction of ribosomes, RNA, and proteins
Biochemistry techniques (northern blotting, western blotting, enzymatic activity assays)

Skills
Strong experience in bacterial genetics, RNA handling, and molecular biology techniques
Keen interest in microbiology and ribosome biology
Critical thinking and ability to contribute to the project both experimentally and intellectually
Open-mindedness, curiosity, and ability to synthesize complex information
Proficiency in English

Contexte de travail

The researcher will be employed by the CNRS. They will be part of the team “Epitranscriptional Responses to Antimicrobial Stress” led by Zeynep Baharoglu in the Microbial Gene Expression Laboratory. This laboratory is part of the Institut de Biologie Physico-Chimique (IBPC), located on the Curie campus in the 5th arrondissement of Paris. The project is supervised by Zeynep Baharoglu. All necessary equipment is already available in the lab or nearby.

Contraintes et risques

Work in a biosafety level 2 (BSL-2) laboratory with the pathogenic species Vibrio cholerae.