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  Structural and Functional Analysis of the Interaction of Dietary Galacto-oligosaccharides with Galectin 3


   School of Chemistry

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Dr A M Hemmings  No more applications being accepted  Self-Funded PhD Students Only

About the Project

An exciting interdisciplinary project is available to explore and exploit the interactions of prebiotic dietary galactooligosaccharides with galectin 3, a member of a family of highly conserved lectins implicated in a host of normal and pathological cellular processes.

Although the beneficial effects of dietary prebiotic oligosaccharides such as galactooligosaccharides (GOS) are known, the exact mechanisms by which they exert their effects are unclear. An unexplored mechanism by which GOS can enhance human intestinal health and prevent gut-related diseases may be through its binding to galectins. The aim of this proposal is to investigate at the biochemical, biophysical and structural level the ability of GOS from prebiotics and plant-based foods to bind to galectin 3 and to assess their ability to compete with intestinal glycoligands such as mucins. The interaction between circulating Gal3 in the bloodstream and cancer cells expressing modified mucin bearing the Thomsen-Friedenreich antigen promotes metastasis suggesting a possible role for antagonists of this interaction as anticancer therapeutics. An aim of the studentship will be the design and testing of GOS-inspired Galectin 3 ligands as potential anticancer agents.

Training will be provided in methods for bioseparation, protein expression and in vitro binding assays (ELISA, carbohydrate arrays). The student will also learn how to investigate protein-ligand binding using a range of physical methods (SPR, ITC and fluorescence titration). Full training will be given in methods of structural biology, particularly X-ray crystallography. Supervision will come from Andrew Hemmings (biophysical methods and structural biology, UEA), Nathalie Juge (glycobiology, IFR), Rob Field (carbohydrate chemistry, JIC) and Charles Brearley (analytical biochemistry, UEA). There may also be opportunity for the student to spend time at the industrial collaborator, Biotempo.

This project is particularly suitable for students with backgrounds in either biology, biochemistry or biological chemistry who wish to gain training in modern biochemical methods.

Acceptable First Degree:
Biochemistry, biological chemistry, chemistry

Minimum Entry Standard: At least a BSc (hons) 2:1 or equivalent.

Funding Notes

Funding is available to EU students. If funding is awarded for this project it will cover tuition fees and stipend for UK students. EU students may be eligible for full funding, or tuition fees only, depending on the funding source.

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