Scientific activity of the SAGAG-Vivès team
Heparan sulfate (HS) is a sulfated polysaccharide that is a major component of the glycocalyx, the thick layer of glycoconjugates found on the surface of most animal cells (1). Thanks to this strategic positioning at the interface between the cell and its external environment, HS encounters, binds and modulates the activity of a multitude of protein ligands, and thus participates in most major cellular processes (2). These extensive biological properties arise from the presence of specific saccharide units within the polysaccharide (3), which structure and sulfation define a "glycocode" gathering recognition and interaction information for the different protein partners. The structure of HS must therefore be finely regulated, to allow the cell to adapt its response to any external stimuli. Recently, it has been shown that a family of sulfatases, the Sulfs, play a major role of glycobiological regulators, by modifying the sulfation of HS and their interaction properties (4).
Our team is particularly interested in this enzymatic mechanism, which represents the only post-synthetic molecular machine able to regulate and modify the glycocode of HS. In this context, our work focuses on studying the structural features of the enzyme (5), its molecular organization, substrate specificities, and the post-translational modifications essential for its activity. We also investigate its enzyme activity and function (6), using in vitro, cell-based and in vivo bioassays available in the laboratory or through the numerous national and international collaborations established on the subject. Finally, we aim to develop inhibitors based on HS mimetics for the development of new anti-cancer therapeutic approaches targeting the Sulfs (7).
Higlights on our latest work on the Sulfs!
CNRS INSB :
CEA IRIG :
ANR, UGA, Glyco@Alps...
National scientific collaborations
Dr. D. Bonnaffé/C. le Narvor, ICMMO, Orsay
Dr. R. Daniel, LAMBE, Evry
Dr. O. Filhol-Cochet, CEA/Biosanté, Grenoble
Dr. F. Lecaille, CEPR, Tours
Dr. B. Marteyn IBMC, Strasbourg
International scientific collaborations
Dr. S. Grazioli/ N. Veraldi, HUG, Genève, Suisse
Dr. C. Reis/ A. Magalhaes, I3S, Porto, Portugal
Dr. A. Russel, Oxford univ., Oxford, UK
Dr. J. van den Born, Groningen univ., Groningen, The Netherlands
Dr. E. Schmidt, Colorado univ., Denver, USA
Dr. X. Yue, Louisiana univ., New Orleans, USA
The GDR « Gagosciences »
Romain Vivès has been coordinator of the GDR CNRS3739 « Gagosciences » (2016-2020). This GDR was created to federate French research teams working on GAGs within a structured network gathering complementary expertise. The aim of the GDR GAG is to promote multidisciplinary research in glycoscience within 3 major disciplinary fields: biology, chemistry and methodological developments.
Romain Vivès is coordinator of the Glyco@Alps IDEX-UGA program. Glyco@Alps explores the fascinating structural diversity and complexity of sugars, including those found in the Alpine biodiversity, and focuses on their exploitation for biopharmaceuticals, medical diagnostics, personalized medicine, materials, environmental sustainability and innovative bio-industries. With the involvement of around 100 scientists of different domains, Glyco@Alps will highlight the University Grenoble Alpes as the first glycoscience center in France.