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Deciphering the glycocode – application of synthetic probes to study protein-carbohydrate interactions

Project Description

All living cells are covered in a coating of complex carbohydrates (glycans) that are attached to lipids and proteins. Specific glycolipids play important roles in controlling cell differentiation, ion transport and cell signaling. However, many viruses, bacteria and protein toxins also exploit these glycans to stick to and enter healthy cells. Glycans can often have multiple binding partners and thus multiple biological roles, which makes understanding the rules of glycobiology (the so-called glycocode) challenging.

In this project we will use enzymes to construct synthetic analogues of an important cell surface glycolipid: ganglioside GM1. We will investigate the effects of selective modification of its hydroxyl groups on its ability to bind to two important sugar-binding proteins (lectins) – galectin-1 and cholera toxin B-subunit. By understanding the roles of each hydroxyl group in the complex we will derive rules for making selective probes that can distinguish between different lectins.

The project will involve a combination of chemical and biochemical methods to produce novel oligosaccharides and glycolipids. You will learn to use biophysical methods including isothermal titration calorimetry to measure the thermodynamics of ligand binding, and X-ray crystallography to determine the structures of complexes to rationalise changes in binding and help decipher the glycocode.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2020:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference and research funding

At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.

EU candidates require 3 years of UK residency to receive full studentship

Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.

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How good is research at University of Leeds in Chemistry?

FTE Category A staff submitted: 34.40

Research output data provided by the Research Excellence Framework (REF)

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