The team “Structural Glycobiology of the Host-Pathogen Interactions” focuses its research on characterizing the glycosylation of micro-organisms and their hosts, with developments in the area of therapeutic agents and analysis tools. We are a trans-disciplinary academic research team regrouping nine researchers with skills ranging from organic synthesis to cell biology.
Our research activity is divided in several complementary topics :
(1) the evaluation of the structure/synthesis/functions relationships of glycosylated pathogenic factors of micro-organisms ;
This topic initially took advantage of the expertise of the group in the structural analysis of complex carbohydrate molecules but was then extended to other techniques thanks to the integration of new researchers mastering complementary skills such as enzymology, genetic engineering and cell biology. Altogether, the objective of our group is to pursue multidisciplinary studies on cell wall glycoconjugates in which we could manage most of the workflow including the production, the structural analysis, the analysis of functions and the identification of biosynthetic pathway. We focused our work on four models : mycobacteria, pathogenic yeasts, Bacillus species and E. coli.
(2) the study of the host glycosylation patterns that may influence pathogenicity.
Along the analysis of the function of the cell wall glyconconjugates of microorganism, we aim to establish the influence of the host glycosylation into the infection process. Thus, within the context of the development of the zebrafish-M. marinum model system, we have conducted throughout analyses of the glycosylation patterns of zebrafish embryos and adults with the ultimate goal of identifying glycosylation epitopes relevant to the infectious process. In parallel, we have initiated the elucidation of the structural and functional changes that take place in the immune cells glycosylation profiles following mycobacterial infection.
(3) the development of chemical or biological therapeutic agents based on saccharides ;
Considering our increasing interest for the glycobiology of pathogenic micro-organism, the design and synthesis of anti-infectious agents, targeting or not glycoconjugates, appeared as a natural developments of our research. This approach was made possible by the integration of several organist chemists in our teams over the past five years. The main developments we are aiming for are new generations of synthetic anti-mycobacterial drugs and natural anti-adhesives based on natural polysaccharides
(4) the development of methods and tools for the study of glycosylation and micro-organisms.
Along our research activities, we are involved into the development of tools for the study of glycosylation. We aim to promote the use of glycoconjugates outside the glycobiologists community for all basic research research domains of biology. Indeed, the functions that glycans play in the physiology and pathophysiology of eukaryotic cells and bacteria are difficult to study by traditional methods that generally require laborious radiolabeling techniques and purification procedures that are incompatible with the in vivo experiments. So, despite the obvious relevance of glycosylation to many biologists, glycobiology is still seen as a confidential area. Thus, the development and dissemination of methods and tools for analysis of glycosylation that are transposable to non-specialized laboratories appear to be the most coherent approach to promote new scientific topics at the interface of biology and sugar chemistry. We are also using these tools within the context of close collaborations with the other groups of the institute to develop new research topics and bring novel insights into their disciplines.
- Structural analysis of glycoconjugates by NMR, mass spectrometry, liquid and gas chromatography ;
- Design and organic synthesis of small molecules including antiparasitic dugs and monosaccharide analogs ;
- Production, purification and enzymatic assays of recombinant glycosyltransferases and glycosidases ;
- Analysis of immunomodulatory activities of glycoconjugates ;
- Fluorescence imaging and electronic microscopy