The sweet tooth of pathogens: therapeutical targets and research tools
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Course and current status

Starting 2016: Director of Centre de Recherches sur les Macromolécules Végétales (UPR5301) CERMAV-CNRS, Grenoble
2013- 2015: Deputy Director of the Chemistry Department CNRS Paris
1999- present: Senior Research Scientist, CNRS Grenoble, France
1999-2015: Head of the group of “Molecular Glycobiology” CERMAV-CNRS
1996-1999: Research Scientist, CERMAV-CNRS
1991-1996: Research Scientist, CNRS, Nantes, France
1989-1991: Post-doctoral fellow at INRA, Nantes.
1988: Post-doctoral fellow at University of Toronto
1988: PhD these Université Grenoble
1984-1988: Junior Research Scientist, CNRS Grenoble.
1984: These 3ieme cycle Paris 6 and ENS Paris
1981 : Agregation de sciences naturelles, ENS Fontenay

Scientific summary

My research interests are in the field of structural glycosciences, with main interest on biologically active oligosaccharides and their interaction with lectins and glycosyltransferases. My present work is focused about lectins from pathogenic microorganisms. On one hand, the characterisation of their interaction with human glyococonjugates and the design of competing glycocompounds open the way for anti-adhesive therapeutical strategies. On the other hand, these lectins can be engineered through synthetic glycobiology strategy for creating new tools in biotechnology, diagnostics and therapy.

 

Abstract

A large number of pathogenic microorganisms display receptors for specific recognition and adhesion to the glycoconjugates present on human tissues.  In addition to membrane-bound adhesins, soluble lectins are involved in infections caused by the bacteria  Pseudomonas aeruginosa  and  Burkholderia cepacia  and by the fungus Aspergillus fumigatus that are responsible  for hospital-acquired diseases. Accumulated knowledge about the structures of the lectins and the interactions with host glycoconjugates has led to the design of powerful glyco-derived inhibitors that can serve as antimicrobial therapeutic agents, as a complement to or an alternative to antibiotic therapy. Design of glycosylated chips, liposomes, fullerenes and other nanoglycoparticles have provided information on multivalent interaction between receptors and cell surfaces. This also result in development of nanomaterials that can be used in diagnostic applications.

Furthermore, the multivalency of lectin is proposed to play a role in their strong avidity for glycosylated cell surfaces and also in their ability to affect membrane dynamics by clustering glycosphingolipids. Bacterial lectins are able to bind to glycoconjugates on human tissues and are therefore thought to be involved in the first step of infection. The role of lectins in membrane invagination indicates that they could also play a role in internalization of intracellular pathogens. Lectins as multivalent and specific compounds are also powerful tools for labeling tumor cells that present altered glycosylation. Engineering of lectins allows the creation of novel supramolecular tools, superlectins, neolectins and Janus lectins with modified architecture, valency and specificity.

 

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