Description du sujet de thèse

The Chemistry and Biotechnology of Oligosaccharides (CBO) team at CERMAV has developed unique expertise in the production of glycans of biological interest by de novo biosynthesis in bacteria whose metabolic pathways have been modified. The project will focus on devising novel synthesis routes to express the enzymes needed to conjugate these glycans onto multivalent architectures, such as peptides or saccharides, with precisely defined and homogeneous molecular structure. The project will encompass molecular biology techniques to construct new bacterial strains, culture in bioreactors, and the purification and characterization of glycoconjugates. Funded for 36 months starting from October 1st, the project will be directed by Sébastien Fort (sebastien.fort@cermav.cnrs.fr) and Emeline Richard (emeline.richard@cermav.cnrs.fr), responsible for the CERMAV microbiology platform.

Context
Many pathogens exploit the glycans present on the surface of our cells to initiate infections. This is particularly evident with influenza viruses and the bacterium Pseudomonas aeruginosa, a common cause of hospital-acquired infections. The widespread use of vaccines and antibiotics to combat these pathogens has led to resistance, diminishing their effectiveness. Consequently, there is an urgent need to develop new antimicrobial strategies. Anti-adhesive therapy presents a promising alternative by designing multivalent glycoconjugates that can strongly interact with pathogens, preventing them from adhering to host cells. Currently, the preparation of these molecules relies on multi-step chemical synthesis. However, this method often results in molecular heterogeneity within the glycoconjugates, making it challenging to ensure their purity and specification. This thesis aims to develop an innovative enzymatic approach that can be industrialized to produce multivalent glycoconjugates with precise molecular definitions.

Contexte de travail

The successful candidate will join the Chemistry and Biotechnology of Oligosaccharides CBO team at CERMAV (UPR CNRS 5301). CBO is a multidisciplinary team at the interface of glycochemistry, biochemistry and microbiology whose research activities focus on the production of oligosaccharides and glycoconjugates for structure-function studies in the fields of human and plant health. CERMAV is located on the Grenoble campus, within easy reach of the city centre by bicycle or public transport. Located in the heart of the Alps, Grenoble is a young university town offering nature lovers a wide range of outdoor activities in both summer and winter.

Skills required
We are looking for a candidate with a keen interest in interdisciplinary projects at the interface between chemistry and biology. He/she should have advanced knowledge of molecular biology, protein expression and enzymology. Knowledge of bio-organic chemistry or glycochemistry would be an asset.