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 (hyperglycaemia) stem from elevated levels of glycolytic intermediates (dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP)) causing oxidative stress and lowering the levels of glutathione and cysteine. Less cysteine in the cell lowers the rate of glutathione biosynthesis, which explains why the glutathione levels are depleted. However, nobody has ever elucidated how and why the cysteine levels are lowered. However, this could be explained by our recent observation that cysteine can chemically react with DHAP and GAP to form thio-hemiacetals.
The aims of this project are:-
1. Detailed characterisation of cysteine reactivity with DHAP and GAP in vitro.
2. Develop chemical and analytical methods to detect and quantify these biochemical reactions under biologically relevant concentrations and conditions.
3. Then use these analytical methods to repeat these analyses with blood cells under hyperglycaemic conditions.
Proving and understanding these new biochemical reactions in vivo will fill a substantial gap in our knowledge of cellular biochemistry in diabetics.
The PhD project offers extensive interdisciplinary training and research experience in biological chemistry, analytical biochemistry, enzymology and cell biology. The project is well suited for a student with a degree in Biochemistry, Biological Chemistry or a related discipline.
For more information on the supervisor for this project, please go here: http://www.uea.ac.uk/pharmacy/people/profile/c-hamilton
Type of programme: PhD
Project start date: October 2019
Mode of study: Full time
Entry requirements: Acceptable first degree - Chemistry, Biochemistry, Biological Chemistry or a related discipline.
The standard minimum entry requirement is 2:1.
Deadline for applications: 31 May 2019
 Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions, VI. Lushchak, Journal of Amino Acids. 2012, doi:10.1155/2012/736837.
 Oxidative stress: A cause and therapeutic target of diabetic complications. E. Araki & T. Nishikawa Journal of Diabetes Investigation. 2010, p90.
 Glutathione Synthesis Is Diminished in Patients With Uncontrolled Diabetes and Restored by Dietary Supplementation With Cysteine and Glycine. RV Sekhar, et al. Diabetes Care, 2011, p162.