Investigating the role of N-type glycosylation in protein-ligand interactions using a unique commercial microarray technology

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.

This is a 4 year IbiolC (http://www.ibioic-ctp.com/) Collaborative Training Partnership (CTP) with BBSRC studentship with Retrogenix Ltd. as the project partner. Support includes stipend and fees at standard Research Council levels.

Applicants should have a First Class or high Upper Second Class Honours degree in biology (molecular, microbiology, biochemistry, biomedical etc.), biological engineering, biotechnology or related degree with excellent technical skills. The project would suit a candidate who has prior technical experience of mass spectrometry, mammalian cell culture or bioinformatic approaches to interpret mass spectra data. As this is BBSRC/IbiolC funding, students must be a home student or EU student (with at least 3 years residency in the UK immediately prior to the PhD).

The successful candidate will receive training in cell culture, tandem mass spectrometry and the use of related bioinformatics tools. The project would suit a biosciences graduate with a strong interest in protein based mass spectrometry.

his is BBSRC CASE award and the candidate will spend approximately three months at the industrial partners site and therefore have first-hand experience in protein ligand screening. This will be excellent experience for a career in biological engineering, one of the fastest growing employment sectors and many of our PhD graduates have found employment in the analytical field through to research and development in biotechnology/biopharmaceutical industries.

The project supervisor currently leads a group of 7 PhD students, 1 PDRA and a Research Technician with access to microbiology and molecular biology facilities as well as cutting-edge mass spectrometers.