PhD Studentship: Exploring the "hidden" intracellular cysteine thiol pool

University of East Anglia - Norwich Medical School

Start Date:  1st October 2017

No. of positions available: 1

Supervisor: Dr Chris Hamilton

Project description:

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.

Person specification: Minimum entry 2:1. The project is well suited for a student with a degree in the Biological Sciences or a related discipline.

Funding notes: Full Studentships cover a stipend (RCUK rate: £14,296pa – 2016/7), research costs and tuition fees at UK/EU rate, and are available to UK and EU students who meet the UK residency requirements.

Students from EU countries who do not meet the UK residency requirements may be eligible for a fees-only award. Students in receipt of a fees-only award will be eligible for a maintenance stipend awarded by the NRPDTP Bioscience Doctoral Scholarships, which when combined will equal a full studentship. To be eligible students must meet the EU residency requirements.

Details on eligibility for funding on the BBSRC website: 

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