Structural and cellular studies on O-GlcNAc and related glycosylations

Lead Research Organisation: University of York
Department Name: Chemistry


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.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
1644614 Studentship BB/M011151/1 30/09/2015 29/09/2019 Alexandra Males
Description Carbohydrate active enzymes assist the formation and breakdown of saccharides. The enzymes are classified into families according to their reaction pathway. The research conducted in this award showed the importance of designing drugs that bind to enzymes along the reaction pathway. This can lead to tightly bound and highly effective drugs. The enzymes investigated in this project were of high interest as they are involved in protein folding, bacterial colonisation and Alzheimer's disease. Novel inhibitors for these enzymes were identified to understand more about the function of the enzymes.
Exploitation Route Identifying the reaction pathways for carbohydrate enzymes could lead to the design of tight binding drugs.
Identifying novel inhibitors could lead to clinical trials and use of these inhibitors as therapeutics.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

Description Wild Overseas Scholars Fund
Amount £1,100 (GBP)
Funding ID N0000504 
Organisation University of York 
Sector Academic/University
Country United Kingdom
Start 05/2017 
End 08/2017
Description Compound analysis 
Organisation Leiden University
Country Netherlands 
Sector Academic/University 
PI Contribution Crystal structure proteins in complex with compounds sent from Leiden.
Collaborator Contribution NMR, chemical analysis and synthesis of the compounds.
Impact 10.1002/cbic.201700080
Start Year 2015
Description Compounds 
Organisation University of Melbourne
Country Australia 
Sector Academic/University 
PI Contribution Crystal structures of proteins in complex with a synthesised compound (either inhibitor or natural substrate/product).
Collaborator Contribution Synthesis of compounds for crystallisation
Impact 10.1021/jacs.6b11247. 10.1002/cbic.201700166
Start Year 2015
Description Computational collaboration 
Organisation University of Barcelona
Country Spain 
Sector Academic/University 
PI Contribution Obtained protein structures with experimental crystallography of compounds of GH125 and GH47 proteins. Resulted in 2 papers.
Collaborator Contribution Computational QM/MM experiments of the proteins GH125 and GH47 in complex with ligands.
Impact 10.1021/jacs.6b11247. 10.1002/cbic.201700166
Start Year 2015