Mucin-Like Glycocalyx Modules for Creating Complex Artificial Glycocalyxes
All cells are covered with a coating of complex carbohydrates (the glycocalyx) and many viruses, bacteria and protein toxins produced by bacteria exploit this sugar coating as a means of binding to and entering their target cells. The glycocalyx on many living cells extends >100 nm from the cell membrane, and its outer portion is dominated by proteoglycans and mucins which have extended and highly glycosylated structures. Interactions of proteins with these glycosylated structures is important for cellular interactions and also may influence the ability of bacterial toxins to reach their primary receptors on the cell membrane. The aim of this project is to construct artificial mucin-like structures that bear blood group antigens and/or tumour-associated carbohydrate antigens and to incorporate them into artificial cells (protocells) and biosensor arrays for protein binding experiments using natural and re-engineered lectins. The tool box of novel glycocalyx complexes that the ESR creates will have applications in developing diagnostic and analytical methods for detecting toxins, parasites or antibodies against tumour antigens.
Through this interdisciplinary project the ESR will develop skills in chemical and enzymatic synthesis of carbohydrates; bioorthogonal ligation chemistry; biophysical techniques for measuring the affinity for molecular interactions; and functionalisation of biomimetic surfaces.
Appropriate training will be provided in all areas that are new to the researcher.
Location: University of Leeds, UK
Supervisor Prof Bruce Turnbull