Accueil > Research > Research groups > Structure and Activity of Glycosaminoglycans Group (H.Lortat-Jacob) > SAGAG-Vivès team
the SAGAG-Vivès teamHead of team : Romain Vivès Scientific activity of the SAGAG-Vivès teamHeparan sulfates (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).
NewsThe SAGAG-Vivès team is recruiting ! We are opening a 18-24 month position for an engineer. He/She will be in charge of this multidisciplinary project, which involves the production of recombinant proteins (in eukaryotic and prokaryotic expression systems), the preparation and screening of oligosaccharide substrate libraries using functional assay (SPR, enzyme assays…) and the functional analysis of Sulf activity using cellular assays (proliferation, migration…). News (archives)Team membersMembers
Alumni (since 2014)
FundingsANR, UGA, Glyco@Alps... Scientific networksNational scientific collaborations
International scientific collaborations
The GDR « Gagosciences » Romain Vivès is coordinator of the GDR CNRS3739 « Gagosciences ». This GDR has been 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.
Glyco@Alps Romain Vivès is member of the executive committee of the Glyco@Alps IDEX-UGA program (coordinator of WP2). 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.
Recent publications Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression Preparation and characterization of Heparan sulfate derived oligosaccharides to investigate protein-GAG interaction and HS biosynthesis enzyme activity Regulation of fractone heparan sulfate composition in young and aged subventricular zone neurogenic niches Interplay between CD44 receptor and passive membrane interactions of soft hyaluronan nano-platelets with cells Hypercholesterolemia in progressive renal failure associates with changes in hepatic heparan sulfate – PCSK9 interaction Proteinuria converts hepatic heparan sulfate to effective proprotein convertase subtilisin kexin type 9 enzyme binding partner Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity HS and Inflammation : A Potential Playground for the Sulfs ? MASP-2 Is a Heparin-Binding Protease ; Identification of Blocking Oligosaccharides Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses A microscale double labelling of GAG oligosaccharides compatible with enzymatic treatment and mass spectrometry Substrate binding mode and catalytic mechanism of human heparan sulfate d-glucuronyl C5 epimerase Heparan sulfate in chronic kidney diseases : Exploring the role of 3-O-sulfation Expression and purification of recombinant extracellular sulfatase HSulf-2 allows deciphering of enzyme sub-domain coordinated role for the binding and 6-O-desulfation of heparan sulfate Mass spectrometry analysis of the human endosulfatase Hsulf-2 A proliferation-inducing ligand-mediated anti-inflammatory response of astrocytes in multiple sclerosis Genetic and enzymatic characterization of 3-O-sulfotransferase SNPs associated with Plasmodium falciparum parasitaemia A jasmonic acid derivative improves skin healing and induces changes in proteoglycan expression and glycosaminoglycan structure High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats Solution structure of CXCL13 and heparan sulfate binding show that GAG binding site and cellular signalling rely on distinct domains The "in and out" of glucosamine 6-O-sulfation : the 6th sense of heparan sulfate. Heparan sulfate-dependent enhancement of henipavirus infection. Langerin-heparin interaction : two binding sites for small and large ligands as revealed by a combination of NMR spectroscopy and cross-linking mapping experiments. Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant mesothelioma . |
