Research overview :
Our research interest are to understand the molecular, cellular and evolutionary mechanisms controlling terminal glycosylation and more specifically sialylation of glycoproteins and glycolipids exposed at the cell surface of living cells. The implication of these sialylated molecules in various biological processes such as cell/cell interaction during development and in various human diseases (genetic diseases, host/pathogens infection or metastasis during cancer progression) has long been known.
Historically, our team studies the sialylation machinery implicated in their biosynthesis and focus on sialyltransferases in both health and disease situations. We seek to understand how and why these highly specific and somewhat redundant glyco-genes have been recruited during animal evolution for specific tasks and functional innovation in vertebrates and we take advantage of animal evolution and biodiversity to study the structure/function relationships of glycosyltransferases.
In parallel, we aim to identify what are the molecular mechanisms underpinning their deregulated expression in human pathologies, in particular in epithelial cancer (breast and colon cancer) to understand the role played by these glycoconjugates in cancer development.
Actually, our current research projects fall into 4 major areas :
1. Genetic and epigenetic regulation of glycosyltransferases.
2. Profiling sialylated carbohydrate antigens and associated GT expression in model cells and in normal and pathological tissues.
3. Comparative genomics and functional analysis of GTs in model organisms like the zebrafish D. rerio.
4. Structure/function relationships of Golgi-glycosyltransferases during evolution and their functional organization in the living cells.
To address these fundamental questions, we use complementary and integrated approaches available in modern biology and comparative genomics. Our approaches are classical biochemical, molecular (molecular cloning, PCR, transcriptional regulation) and cell biology (cell culture and transfection, confocal microscopy) approaches and analytical glycomics approach for glycan profiling. In addition, we have developed innovative approaches of molecular phylogeny and phylogenomics using bioinformatic tools (datamining of GT homologous sequences, GT database) and functional glycomics in animal models such as zebrafish Danio rerio.