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Investigation of carbohydrate processing enzymes involved in heart disease

School of Biology

Sunday, December 13, 2020 Competition Funded PhD Project (Students Worldwide)

About the Project

Various types of carbohydrates, or sugars, are ubiquitous throughout nature and perform a number of important functions in our cells. Carbohydrates can exist in long chains, composed of one or more types of monosaccharides, which is how energy is stored in cells from the food we ingest, why wood is strong, and is responsible for the molecular glue that sticks our cells together. At the other end of the scale, single or small groups of specialized monosaccharides can be appended to other biomolecules such as proteins and lipids, where they work to coordinate cell processes such as inter- and intra-cellular signalling, and defence against pathogens. The structure and sequence of carbohydrates are complex and highly variable, but unlike DNA there is no genetic code that can be read to determine how it should exist. Instead, carbohydrate structure and sequence are defined only by the enzymes that synthesize, degrade and modify the carbohydrate molecules.

Heart disease kills 17 million people per year worldwide. A build-up of fatty deposits in the arteries, called plaques, means oxygenated blood does not reach the heart. Interestingly, patients with heart disease often correlates with them having oral bacterial disease. Recently it was shown there are bacterial species found in plaques in both the mouth and arteries. These bacteria make a protective biofilm for protection, which forms part of the plaque. The bacteria in the biofilm cannot obtain nutrition easily, and so need enzymes that break down carbohydrates for energy. The aim of the project is to understand how these enzymes function. If enzyme inhibitors are identified, biofilm growth and hence plaque formation could be limited, thus impacting progression of heart disease.

This project will be inter-disciplinary using a range of techniques including molecular biology, protein biochemistry, enzymology, structural biology (X-ray crystallography) and microbiology. Work will involve expression and characterization of the enzyme, crystallisation and structure determination of the protein in complex with substrates/products, enzyme assay development, testing inhibitors, and exploring the effect on biofilm production and bacterial growth. The project will equip the student with a wide range of techniques, both in the laboratory and transferable skills such as writing, presentations, time management, exploration of own ideas, and organisation.

Any informal enquiries can be directed to Dr Tracey Gloster ().

Keywords: Biochemistry, structural biology, enzymology, glycobiology.

Applications can be made online via our online portal-

Funding Notes

First class or 2.1 BSc degree (or equivalent) in biochemistry, molecular biology, chemistry, or related subject. An undergraduate/postgraduate Masters qualification and/or relevant research experience strengthens the application.

Funded by the School of Biology, University of St Andrews. The studentship covers tuition fees (Home and Overseas) and a living allowance for a duration of 3.5 years.

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