Site-specific glycosylation of oncogenic drivers using genetic code expansion

Supervisors: Frédéric BARD, Lucile ROUYER and Krittalak May CHAKRABANDHU

Project

Glycosylation is the most common post-translational modification of proteins. Our group in Marseille has identified a pathway, called GALA, through which cancer cells hyper-O-glycosylate a range of cell-surface receptors and extracellular matrix (ECM) proteins. GALA is activated in a large fraction of solid tumors, strongly promotes tumor growth, and is essential in cancers such as liver and pancreatic cancer. How changes in the glycosylation of surface and secreted proteins produce such strong effects remains unknown. More broadly, how a glycan affects the function of an individual protein is a key question that is still poorly understood.

This project aims to establish a new strategy that combines genetic code expansion (GCE) with bioorthogonal click chemistry. The goal is to install glycans at specific sites on cancer-relevant cell-surface proteins and directly study the functional consequences in cancer.

GCE, developed in the team of Krittalak CHAKRABANDHU in Nice, allows a noncanonical amino acid (ncAA) carrying a unique chemical handle to be incorporated at a chosen position in a protein. This is done by introducing an amber stop codon at that position and supplying a dedicated orthogonal tRNA/aminoacyl-tRNA synthetase pair. The chemical handle can then be used to attach molecules, here glycans, by bioorthogonal click chemistry.

The primary objective of the two Master’s projects is to establish and validate a method for site-specific glycan addition. This approach could provide a general platform for experimentally manipulating disease-associated glycosylation with unprecedented site specificity.

Required profile

We are looking for two Master 2 candidates, one in the BARD team and one in the CHAKRABANDHU team. The two students will work in parallel on the project, one on an ECM receptor and the other on an ECM protein, using the same techniques in both labs. We are looking for motivated candidates interested in developing innovative methods in glycosylation and GCE. Strong communication skills and proactivity are expected, as the project is interdisciplinary and involves close interaction between teams.

Internship details

• Dates: 4 January 2027 to 30 June 2027
• Meetings: weekly joint meeting between the two labs
• Internship 1: CRCM, Marseille, BARD team
• Internship 2: Institut de Biologie Valrose, Nice, CHAKRABANDHU team (Genetic Code Expansion Facility)

How to apply

Please send your application to Dr Lucile ROUYER. Application can be sent in English or French. Let us know whether you are interested in the internship in Marseille or in Nice.