2nd Supervisor: Dr Jane Goodall
Outline of project:
Most autoimmune diseases have a very strong genetic basis with polymorphic genetic variants altering the function of immune cells giving rise to chronic autoimmune inflammation. In previous work we showed that a variant of the PTPN 22 gene which is strongly associated with a number of autoimmune diseases including rheumatoid arthritis, produced neutrophils which were hyperactive to activation producing increased levels of reactive oxygen species (1,2).
However, genes alone are not enough and there is strong evidence that environmental factors such as infection, diet or smoking can contribute to the precipitation autoimmunity.
In previous work (unpublished) we have shown that cigarette smoke extract can alter the activity of PTN22, probably through oxidative inactivation, and so interferes with signalling in T lymphocytes. We hypothesise that the variant PTPN 22 may synergise with the effects of cigarette smoke to produce aberrant immune cell responses and so promote autoimmunity.
The student will test the hypothesis that cigarette smoke extract alters signalling in primary T cells thus promoting the generation of TH1 and TH 17 and so promoting inflammation.
The effects of cigarette smoke extract on primary human T cells will be assessed to investigate changes in signalling pathways but also focus on assessing whether the inhibitor or cigarette smoke extract promote the differentiation of T cells towards inflammatory phenotype as judged by their production of pro inflammatory cytokines.
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:
Applications should be directed to Dr Stephen Young (email [email protected]
). 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.
Bayley R, Kite KA, McGettrick HM, Smith JP, Kitas GD, Buckley CD, Young SP. The autoimmune-associated genetic variant PTPN22 R620W enhances neutrophil activation and function in patients with rheumatoid arthritis and healthy individuals. Ann Rheum Dis. 2015;74(8):1588-95.
Rider DA, Bayley R, Clay E, Young SP. Does oxidative inactivation of CD45 phosphatase in rheumatoid arthritis underlie immune hyporesponsiveness? Antioxidants & Redox Signaling. 2013;19(18):2280-5.