Structural and cellular studies on O-GlcNAc and related glycosylations

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The control of cellular function through the co- and post-translational O-GlcNAc modification is one of the emerging themes of modern cell biology. Of particular note is the link to neurodegenerative diseases, notably the tauopathies, where the modification stabilizes tau and reduced toxic aggregation and Parkinson's disease. The PhD will study the molecular basis of the O-GlcNAc, and related, glycosylations through a combination of X-ray crystallography, inhibitor design and analysis, rational protein engineering and chemical biology. The ultimate goal is to provide a structural and mechanistic description of the human enzyme system and to use this to inform cellular studies probing enzyme inhibition in a therapeutic context.