Project description DEENESFRITPL Insight into sugar-processing enzymes opens new applications in medicine and biotechnology Enzymes that produce and degrade oligosaccharides and generate glycoconjugates have a variety of applications in medicine, the food industry and the energy sector for biofuel production. The EU-funded CARBOCENTRE project aims to provide more insight into the active centre of these glycoprocessing enzymes using biochemical and 3D structural analysis approaches. Unveiling the structure of enzymes through theoretical and computational chemistry will aid the design and synthesis of novel inhibitors as lead compounds against diseases such as cancer. Moreover, scientists will discover and optimise new enzymes suitable for various biotechnology and health applications. Show the project objective Hide the project objective Objective Enzymes that produce and degrade oligosaccharides and glycoconjugates are present in all kingdoms of life. The ability to visualize, modulate and understand these carbohydrate-active enzymes (CAZymes) therefore offers great potential for human health and sustainable industries. To provide a “disruptive” shift in our understanding, we adopt in this proposal a multidisciplinary approach combining structural biology, enzymology, computational chemistry, organic synthesis, and chemical biology, with major leaders in these fields part of our CARBOCENTRE Synergy Team. Three fundamental strands will specifically target and ‘capture’ glycoprocessing enzyme active sites. Biochemical and 3-D structural analyses will inform computational dissection of the reaction coordinate of key enzymes for human health and biotechnology processes. Building on our founding work on retaining glycosidases we will also target inverting glycosidases and glycosyltransferases. Following fundamental analyses, our probes will feed research in two major application domains of human health and biotechnology: 1. To provide visualization, diagnosis, and inhibitor assays and clinical lead compounds for enzymes in cancers and genetic diseases (lysosomal storage disorders). 2. To explore the natural diversity of CAZymes and to discover, quantify and optimize new enzymes for food and household applications and for biomass conversion to biofuels. In an iterative cycle, structural biology and enzymology (Davies, York), will inform, through structures of enzymes and enzyme-inhibitor complexes, theoretical and computational chemistry (Rovira, Barcelona), which in turn will guide the design and synthesis (Overkleeft, Leiden), of inhibitors and activity-based probes for ensuing chemical biology studies in the domains of biomedicine and biotechnology. Fields of science medical and health sciencesclinical medicineoncologyengineering and technologyindustrial biotechnologybiomaterialsbiofuelsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesagricultural sciencesagricultural biotechnologybiomassnatural sciencesbiological sciencesmolecular biologystructural biology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2020-SyG - ERC Synergy Grant Call for proposal ERC-2020-SyG See other projects for this call Funding Scheme ERC-SyG - Synergy grant Coordinator UNIVERSITEIT LEIDEN Net EU contribution € 3 768 875,00 Address Rapenburg 70 2311 EZ Leiden Netherlands See on map Region West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (3) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITEIT LEIDEN Netherlands Net EU contribution € 3 768 875,00 Address Rapenburg 70 2311 EZ Leiden See on map Region West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITAT DE BARCELONA Spain Net EU contribution € 1 984 750,00 Address Gran via de les corts catalanes 585 08007 Barcelona See on map Region Este Cataluña Barcelona Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITY OF YORK United Kingdom Net EU contribution € 3 303 625,00 Address Heslington YO10 5DD York north yorkshire See on map Region Yorkshire and the Humber North Yorkshire York Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
