A doctoral position is available in the Biocatalysis team at the laboratory of chemistry and biology of metals (LCBM) at the CEA in Grenoble - France to work on the biochemistry and biology of the biogenesis of iron-sulfur clusters in mycobacteria to develop new treatments for tuberculosis.

Despite being the target of one of the oldest vaccines still in use, and also targeted by specific antibiotics, tuberculosis remains a major public health problem, responsible for 1.6 million deaths a year worldwide. One of the main difficulties in combating against tuberculosis with antibiotics lies in the ability of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, to enter a state of dormancy in macrophages and pulmonary lesions (granulomas). Most antibiotics are ineffective against this dormant state of Mtb. It is therefore necessary to find molecular targets that are active both in Mtb's active state and in its dormant state. Proteins containing iron-sulfur (Fe-S) cofactors are one attractive family of targets. The genome of Mtb contains around 60 open reading frames encoding putative Fe-S proteins, which hold important functions both in active and dormant states of Mtb. An attractive way to target all of these Fe-S proteins at once would be to target the pathway responsible for the biogenesis of Fe-S clusters in Mtb. In general, bacteria contain several Fe-S cluster biogenesis systems (ISC, SUF and/or NIF). Interestingly, Mtb contains a single system for Fe-S cluster assembly, namely the SUF system. This system is absent in human, where Fe-S assembly is sustained by other machineries. The PhD project aims to explore the feasibility of using the Fe- S center assembly pathway, i.e. the SUF, as a molecular target in the fight against tuberculosis. To this end, a part of the project will consist in the validation of essentiality of the SUF system in Mtb pathogenicity. Another part will be devoted to the functional and structural characterization of Mtb SUF proteins. A third part will be focused on the identification of inhibitors of the Mtb SUF system as potential antibacterial agents.

The project will be realized using a combination of experimental approaches including mycobacterial genetics and physiology, biochemistry, spectroscopy, structural biology, in vitro and in vivo models of Mtb infection.

The candidate will focus on the functional and structural characterization of Mtb SUF proteins, and on the identification of inhibitors of the Mtb SUF system through a target-based whole cell screening approach.

Our laboratory is equipped with gloveboxes to work under anaerobic conditions to purify and characterize the SUF proteins. The candidate will benefit from a highly stimulating environment to afford a future career either in academia or in R&D.

The candidate should hold a Master degree in biochemistry, structural biology or equivalent and some previous wet-lab experimental experience. He/she should have good knowledge in protein expression and purification. A strong background in chemistry and enzyme mechanisms would be an advantage. We are looking for a highly enthusiastic and open-minded candidate with good communication skills who likes to work in a multidisciplinary team.

This corresponds to a 3-year contract with a monthly gross salary of 2200€.

Starting date: September/October 2024​

To apply, please provide a detailed resume, transcripts of records, a cover letter and two reference letters to Sandrine Ollagnier, head of the Bocatalysis team. You can contact her for further information.​