How does the genetic variant of PTPN22 regulate macrophage metabolism and signalling?

Outline of Project:
A genetic variant of the protein tyrosine phosphatase PTPN22, in which arginine 620 is changed to a tryptophan (R620W), is the most widely distributed polymorphism associated with a broad range of autoimmune disease. This includes rheumatoid arthritis, lupus and type I diabetes. We have shown that neutrophils expressing this variant are hyperactive and so may contribute to the inflammatory disease processes in autoimmunity. Preliminary data shows that this also affects the function of macrophages, and intriguingly also affects the metabolism of these cells.

We have shown that metabolic profiling using NMR spectroscopy of serum and urine of rheumatoid arthritis patients can predict outcome early in disease and can also predict responses to therapeutic intervention. The source of the metabolites in the blood and urine may be partly from the inflamed synovium tissue in the joints. However, another significant source of metabolites may be activated immune cells both locally and systemically and macrophages are likely to contribute in a significant way to these metabolites.

The student will test the hypothesis that macrophages expressing the PTPN22 will have a signature metabolic profile which will indicate significant differences in their function. This may show how they contribute to driving the chronic immune inflammation associated with rheumatoid arthritis.

Person Specification:
Applicants should have a strong background in biochemistry, and ideally a background in immunology. They should have a commitment to research in the mechanisms driving human disease and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.

How to apply:
Informal enquiries should be directed to Dr Stephen Young
Applications should be directed to Dr Stephen Young (email [Email Address Removed]). To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.