Investigating the Role of N-Type Glycosylation in Protein-Ligand Interactions Using a Unique Commercial Microarray Technology

Lead Research Organisation: University of Sheffield
Department Name: Chemical & Biological Engineering

Abstract

Over recent years microarray technology has been instrumental in expanding knowledge of the interactions between proteins and both synthetic and natural ligands, contributing to substantial advances in the global biopharmaceutical industry. Retrogenix Ltd. specialises in the production of unique cell microarrays, expressing thousands of full length human plasma membrane and secreted proteins. The advanced technology allows identification of interactions between proteins and potential ligands for biopharmaceutical clients. It is used for the discovery of novel therapeutics, identification of promising drug targets and safety assessment of drug candidates.

There are a range of binding mechanisms and these can be affected by covalent modifications to the proteins, referred to as post-translational modifications. Glycosylation is the addition of glycans (sugars) to proteins and is the most complex post-translational modification of human proteins. Glycans affect protein structural and functional attributes including biological activity, half-life and cell targeting. It is a highly heterogenous process that is impacted by factors such as environmental conditions, and hence the manufacturing process would almost certainly affect the glycosylation profile of the membrane and secreted proteins. Hence, glycosylation could significantly impact on protein-ligand binding characteristics.

This project aims to better understand how the process of sugar addition (N-glycosylation), affects both proteins and ligand interactions, and ultimately create a more diverse and powerful screen as well as helping to identify more "potent" cell interactions.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/V509231/1 01/10/2020 23/05/2025
2493266 Studentship BB/V509231/1 08/02/2021 07/02/2025 Helen Louise Wright