Description du sujet de thèse

The objective of this project is to resolve the structure/activity relationships of Lpp binding to the bacterial cell wall by LdtA,B,C transpeptidases. Cells that lack it have greater membrane permeability and sensitivity to antibiotics due to increased permeability of their outer membrane. Therefore, targeting the binding of the Lpp to the peptidoglycan layer should eliminate bacteria in patients.

Activities :

Study the structure of different Ldt and their interaction with peptidoglycan and Lpp using NMR and/or X-ray crystallography. These structural studies will be complemented by biochemical and biophysical analysis of the characteristics of Ldt/peptidoglycan/Lpp interactions. The observations made will be validated in vivo at the level of the BREAKthrough consortium. In parallel, molecular docking studies will be carried out with substrates and inhibitors and different biophysical methods will be used to characterize the interaction between Ldt and inhibitors synthesized by other groups of the BREAKthrough consortium. As part of this thesis, 6 months will be dedicated to scientific stays in three public and private laboratories of the consortium.

Contexte de travail

Located on the Polygone scientifique de Grenoble (ESRF/ILL/EMBL/IBS), the Institute of Structural Biology (IBS) is a national and international player in the field of integrated structural biology. At the same time research center, technical platform, host site and scientific training, the IBS aims to develop research in structural biology, a field of research crucial for the understanding of fundamental biological mechanisms. It is based on 12 state-of-the-art platforms. As a joint research unit (CEA-CNRS-UGA) IBS is composed of 19 research groups, each of these groups proposing a multidisciplinary approach, at the interface of biology, physics and chemistry, in coherence with 3 research axes. Nearly 300 people work at IBS, researchers, doctoral students, engineers and technicians in a multicultural and international environment. The person recruited will join the NMR group that works on the bacterial cell wall.

Contraintes et risques

To be eligible to apply for this position as part of the European BREAKthrough project, candidates must meet the following criteria.
- You have not yet obtained (or successfully defended) a PhD.
- You have not resided or carried out your main activity (work, studies, etc.) in the country of the institution recruiting you for more than 12 months during the 36 months immediately preceding your date of entry into service. Compulsory national service, short-term stays such as holidays and time spent in a procedure for obtaining refugee status are not taken into account.
- The research will be done indifferently in French or English, however it is expected that the non-French-speaking candidate strives to learn the basics of French in order to facilitate communication and its integration into the laboratory.

Informations complémentaires

Gross monthly salary: €2945
Variable part according to family situation
The salary for this thesis is higher because it is a Marie Curie Horizon contract