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Mechanistic, structural, and functional studies of a human carbohydrate processing enzyme

  • Full or part time
  • Application Deadline
    Sunday, December 01, 2019
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Carbohydrates, or sugars, are ubiquitous throughout nature and perform a number of important functions in our cells. Carbohydrates can exist in long chains, polysaccharides, 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, a single or a few sugars can be appended to other biomolecules such as proteins and lipids and are important in cell processes such as signalling and defence against pathogens. The structure and sequence of carbohydrates is 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 is defined only by the enzymes that synthesize and degrade the carbohydrate molecules.

We are interested in a human carbohydrate processing enzyme, hexosaminidase D, that is reported to play a role in diseases such as rheumatoid arthritis. However, there have been few studies done to characterise the enzyme at the molecular level; the physiological substrate and function it performs in cells is not known. The aim of the PhD would be to perform studies to aid the mechanistic, structural and functional understanding of this enzyme. This would be a multi-disciplinary project and would involve learning skills including molecular biology, recombinant protein expression and purification, protein characterization, enzyme kinetic assays, structural biology (X-ray crystallography) and cell biology. Our collaborators will synthesize inhibitors, which will be tested with the enzyme for potency and specificity. The goal of the project would be to develop specific inhibitors of the enzyme (aided by structural information) and to test these in cells to establish the effect of inhibiting the enzyme on cell function and viability.

Informal enquiries are welcome. Please contact Dr Tracey Gloster directly:

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.
Funding: Fees and stipend is provided for 3.5 years.

References

1. Gutternigg M, Rendić D, Voglauer R, Iskratsch T, Wilson IB. Biochem J, 2009, 419, 83-90. Mammalian cells contain a second nucleocytoplasmic hexosaminidase.
2. Alteen MG, Oehler V, Nemčovičová I, Wilson IB, Vocadlo DJ, Gloster TM. Biochemistry, 2016, 55, 2735-47. Mechanism of Human Nucleocytoplasmic Hexosaminidase D.

How good is research at University of St Andrews in Biological Sciences?

FTE Category A staff submitted: 50.45

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

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