PhD Opportunity – Exploring the roles of methionine sulfoxide reductases in mammalian cells

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Project description: Methionine oxidation is an enigmatic, stereo specific posttranslational modification of proteins that is traditionally thought to be a result of oxidative damage. Cells express enzymes that act as methionine sulfoxide reductases (Msr) with two distinct families, MsrAs and MsrBs acting on the S and R epimers, respectively. Intriguingly, the mammalian endoplasmic reticulum, an oxidising compartment of the cell, is only known to contain one Msr, MsrB3, leaving open the question as to whether methione-S-sulfoxide can be repaired in this location and indeed whether MsrB3 acts as a reductase or an oxidase. Defects in MsrB3 expression or function are linked to health conditions including deafness indicating that it is worthy of further study. In this project, you will explore MsrB3 function at the structural and cellular level exploiting new chemical biological tools in collaboration with Prof Hartley (School of Chemistry).

Techniques used:

1. Biomolecular NMR spectroscopy,
2. Protein X-ray crystallography,
3. Biochemical assays,
4. Chemical biology tool compounds,
5. Cell biology

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