MRC DTP 4 Year PhD Programme: Proteomic approaches to understanding the role of IL-33 in immune mediated disease
Dr S Arthur
Prof D Cantrell
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
This project is part of our exciting and challenging University of Dundee 4-year MRC DTP Programme in Quantitative and Interdisciplinary approaches to biomedical science. This PhD programme brings together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. Further information on the programme structure and training can be found at https://www.dundee.ac.uk/study/pg/phds/dtp/mrc-dtp/
While the immune system plays a critical role in combating infection, inappropriate regulation of immunity has a pathogenic role in many diseases including autoimmunity, allergic disease and cancer. IL-33 is a member of the IL-1 family that is released by damaged endothelial and epithelial cells. IL-33 release acts as a “danger” signal to activate inflammation. It is involved in the response to both helminth and fungal infections and is also known to play a pathogenic role in allergic diseases such as asthma. IL-33 acts on a subset of immune cells, including type 2 innate lymphoid cells and mast cells. It has a number of effects on these cells including driving proliferation and the production of Th2 cytokines such as IL-13.
While IL-33 plays important roles in infection and disease, the intracellular signaling networks it uses are not fully understood. In mast cells we have previously shown a critical role for the p38 MAPK pathway in mediating IL-33 induced cytokine production (1). This project will expand on these findings and use global proteomic approaches to map signaling networks in IL-33 stimulated cells. This will then be used to delineate the pathways required for the effects of IL-33 on mast cell and type 2 innate lymphoid cell function. Interventions in these pathways will then be examined in the context of allergic disease to identify potential new targets for drug development.
1: McCarthy PC, Phair IR, Greger C, Pardali K, McGuire VA, Clark AR, Gaestel M & Arthur JS, (2018) IL-33 regulates cytokine production and neutrophil recruitment via the p38 MAPK-activated kinases MK2/3. Immunol Cell Biol. doi:10.1111/imcb.12200. PMID: 30171775.
2: Liew FY, Girard JP & Turnquist HR, (2016) Interleukin-33 in health and disease. Nat Rev Immunol. 16(11):676-689. PMID: 27640624.
3: Arthur JS & Ley SC, (2013) Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol. 13(9):679-92. PMID: 23954936.