Exploring the “hidden” intracellular cysteine thiol pool. (HAMILTON_U17DTP)

University of East Anglia
October 31 2016
Position Type
Full Time
In humans, the cysteine-containing tripeptide glutathione (GSH) is an essential thiol cofactor that maintains an intracellular reducing environment to protect against oxidative stress reactive oxygen species, which cause lipid, protein & DNA damage.

Glutathione biosynthesis is limited by the availability of cysteine. In diabetics, many of the long term complications arising from high glucose levels stem from elevated levels of glycolytic intermediates (DHAP and GAP) causing oxidative stress and lowering the levels of glutathione and cysteine. Less cysteine in the cell reduces the rate of glutathione biosynthesis, which explains why the glutathione levels are reduced. However, nobody has ever elucidated how and why the cysteine levels are reduced. We have recently shown that cysteine can chemically react with DHAP and GAP to form thiohemiacetals. This could explain what cysteine levels are reduced.

The aim of this project is first to explore these reactions in detail in solution and ultimately to repeat these analyses in live cells in order to prove is occurs in living systems. Proving and understanding the new biochemical reactions in vivo will fill a substantial gap in our knowledge of cellular biochemistry ion diabetics. It will also establish an alternative sink for cysteine in cells whose relevance permeates across all living organisms.

The project offers extensive interdisciplinary training and research experience in analytical biochemistry, enzymology, whole cell NMR spectroscopy and cell biology. This will involve working within three different research groups within the School of Pharmacy and The School of Biology.

The project is well suited for a student with a degree in the Biological Sciences or a related discipline.

This project has been shortlisted for funding by the Norwich Biosciences Doctoral Training Partnership (NRPDTP). Shortlisted applicants will be interviewed as part of the studentship competition. Candidates will be interviewed on either the 10th, 11th or 12th January 2017.

The Norwich Biosciences Doctoral Training Partnership (NRPDTP) offers postgraduates the opportunity to undertake a 4 year research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three month professional internship (PIPS) during their study. The internship offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.

For further information and to apply, please visit our website: www.biodtp.norwichresearchpark.ac.uk

This job comes from a partnership with Science Magazine and Euraxess