Objectif The development of new approaches to dissect the diverse roles for carbohydrates in living cells is a major challenge for modern cell biology. The huge diversity of carbohydrates is reflected in a multiplicity of function; in addition to acting as energy sources, carbohydrates play major roles in structure, signalling and epigenetics. The work programme will build upon the applicant’s excellence in the mechanistic and structural enzymology of carbohydrate-active enzymes to tackle the key challenges of modern cellular glycobiology. Our vision is to provide fundamental structural and mechanistic-dissection of key proteins and their complexes and to use these as the foundation to deliver enzyme inhibitors as tools to probe the cellular function of specific glycans. The programme’s three strands will each scale a major pinnacle of carbohydrate biochemistry. Strand 1 will focus on mammalian glycosidases involved in glycocerebroside metabolism and genetic disease. We will unlock new 3-D information for glycocerebrosidase 2 (GBA2) and use these together with GBA1 to design and exploit novel and specific enzyme inhibitors as mechanistic and cellular probes, novel chaperones and imaging agents. Strand 2 will focus on the key endoplasmic reticulum enzyme endomannosidase, both its mechanistic novelty and its exploitation to perturb cellular glycans to unlock its biological roles and deliver compounds for anti-viral therapeutics. Strand 3 will probe the modification and elaboration of specific human N-glycans and their role in cell surface receptor biology. It will focus on the GlcNAc transferase V catalysed formation of polylactosamine epitopes and their regulation of growth factor signalling at the cell surface both in health and cancerous tissues. GlycoPOISE will both answer cardinal structural and chemical mechanistic questions in the enzymology of glycobiology and inform strategies for the observation and inhibition of carbohydrate-active enzymes and their exploitation Champ scientifique natural sciencesbiological sciencescell biologynatural sciencesbiological sciencesbiochemistrybiomoleculescarbohydratesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesbiological sciencesgeneticsepigenetics Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Appel à propositions ERC-2012-ADG_20120314 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil UNIVERSITY OF YORK Contribution de l’UE € 2 500 000,00 Adresse HESLINGTON YO10 5DD York North Yorkshire Royaume-Uni Voir sur la carte Région Yorkshire and the Humber North Yorkshire York Type d’activité Higher or Secondary Education Establishments Chercheur principal Gideon John Davies (Prof.) Contact administratif Chris Barber (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITY OF YORK Royaume-Uni Contribution de l’UE € 2 500 000,00 Adresse HESLINGTON YO10 5DD York North Yorkshire Voir sur la carte Région Yorkshire and the Humber North Yorkshire York Type d’activité Higher or Secondary Education Establishments Chercheur principal Gideon John Davies (Prof.) Contact administratif Chris Barber (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée