Description du sujet de thèse

The human gut microbiota (HGM) is a complex microbial community that inhabits our intestinal tract. Its crucial role in human health is now established. The HGM is mostly composed of bacteria with roles on our health as diverse as energy harvest, vitamin production or protection against pathogens. Microbiota bacteria use complex glycans as carbon source, especially those present at the surface of the gut cells, thereby contributing to maintaining the epithelium integrity. A small fraction of the HGM, termed the mycobiota, is composed of commensal yeasts which can give rise to serious infections. The interaction between these yeasts and the host has been demonstrated, but their ability to degrade and use host complex glycans remains to elucidate at the functional level.

The proposed project aims at studying host glycan enzymatic degradation by the microbiota yeasts, at the molecular level. This will include heterologous production of putative glycan degrading enzymes in the yeast Pichia pastoris, their purification using chromatography techniques, and in depth biochemical and structural characterization. Ultimately, this project will be a first step towards understanding the interaction between host glycans and microbiota yeasts. The successful candidate will be involved in every step of the project, lead the experiments, analyze and present the data.

Contexte de travail

The project will be led at CERMAV (Center for Research on Plant Macromolecules) a CNRS lab located at Grenoble, France, in the « Molecular and Structural Glycobiology » team, under the supervision of Dr. Marie Couturier. The CERMAV is a multidisciplinary glycoscience lab with a variety of approaches combining chemistry, physicochemistry and biology. The Molecular and Structural Glycobiology team is led by Dr Annabelle Varrot and gathers 15 to 20 people studying lectins and carbohydrate active enzymes by a range of approaches such as bioinformatics, protein production, biochemistry and structural biology. The PhD student will have access to all necessary equipments and expertise to successfully carry out his/her research.

The position is intended for a highly motivated student with excellent scientific skills and good capacity to communicate and interact within the team. A master degree (or equivalent) in microbiology/biochemistry is required, with skills in enzymology. Knowledge in glycosciences will be appreciated.

This 36-months full-time PhD position is funded by the ANR (National Research Agency) starting September 1st