Missions

This CNRS pre-maturation funded project aims to accelerate the development of new classes of antibiotic compounds targeting the bacterial processivity ring, also known as the β-clamp. The World Health Organization (WHO) has identified the ESKAPE pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp.) as priority targets for the discovery of new antibiotics. These pathogens are major causes of hospital-acquired infections, many of which have developed resistance to current treatments.
In recent years, with the aim to inhibit DNA replication in Gram-negative bacteria, we have designed peptide-based molecules capable of effectively blocking the interaction site of the bacterial β-clamp. This essential protein acts as a platform for anchoring DNA polymerases - enzymes responsible for DNA replication - allowing them to remain bound to DNA and ensuring their high processivity. The goal of this project is to rationally design and synthesize optimized analogues of these peptides, guided by structural and biophysical data, using a recently developed approach in our group that enhances antibacterial potency. The most promising candidates, selected for their activity against an expanded panel of bacteria, will then be tested in an animal infection model.

Activités

- Perform multi-step organic synthesis in solution and on solid support
- Conduct peptide synthesis
- Apply standard purification and analytical techniques for organic molecules
- Write research reports and draft scientific publications
- Present results during internal group meetings and seminars

Compétences

-PhD ( less than 3 years) in organic chemistry, with demonstrated expertise in bioorganic or medicinal chemistry
-Strong motivation and a solid academic background
-Excellent organizational and teamwork skills
-Proficiency in English (written and spoken) is highly desirable
-Strong writing and presentation skills
-Autonomous, rigorous, and proactive attitude, with a strong motivation to efficiently produce target molecules for biological evaluation
Structure, Dynamics and Targeting of Biomolecular Machines team at the Institute of Molecular and Cellular Biology (IBMC) in Strasbourg.

Contexte de travail

This project, at the interface of organic and peptide chemistry, will be carried out primarily in Gilles Guichard's group at the Institute of Chemistry and Biology of Membranes and Nanoobjects (CBMN), within the European Institute of Chemistry and Biology (IECB) in Pessac, France.
CBMN and IECB are dynamic, interdisciplinary research centres located on the University of Bordeaux campus. The laboratory is fully equipped for chemical synthesis, and the institute hosts state-of-the-art technology platforms for physicochemical analysis (NMR, mass spectrometry, X-ray diffraction, etc.).
This pre-maturation project represents the first step in the technology transfer process and is conducted in close collaboration with the Structure, Dynamics and Targeting of Biomolecular Machines team at the Institute of Molecular and Cellular Biology (IBMC) in Strasbourg.

Contraintes et risques

Standard health and safety precautions apply due to the handling of chemical reagents. All synthesis experiments will be conducted in a fully equipped laboratory under fume hoods at the IECB