This project is one of 19 four year PhD Studentships funded by Medical Research Scotland (https://www.medicalresearchscotland.org.uk) to be delivered jointly by the named University and External Partner Organisation (EPO). The Studentship will provide the first-class academic and additional training provided by the EPO needed to equip the successful candidate for a science career in an increasingly competitive market.
"PIM kinase inhibition as a therapeutic approach in IL-15-driven autoimmune diseases " to be delivered by the University of Dundee [Supervisors: Dr Mahima Swamy and Dr Yogesh Kulathu (both MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee)] and AstraZeneca UK Limited (www.astrazeneca.com) [External Partner Organisation supervisor: Dr. Werngard Czechtizky].
A hallmark of autoimmune diseases including the intestinal inflammatory disorder, coeliac disease, is the overexpression of IL-15. We recently identified the PIM kinases as key mediators of IL-15 signalling in intestinal immune cells that drive intestinal damage. Indeed, loss of these kinases in animal models leads to reduced activity of the immune cells that drive Coeliac disease, so that they cannot destroy the gut lining. Building on these important findings, this project aims to establish the PIM kinases as therapeutic targets for the treatment of Coeliac disease, and potentially other organ-specific autoimmune diseases that are driven by IL-15. Importantly, drugs targeting the PIM kinases are currently in clinical trials for treatments of many cancers, and could be repurposed for treatment of other diseases. We will explore the relevance of using these drugs to target PIM kinases for treatment of Coeliac Disease, as well as other IL-15 mediated inflammatory autoimmune diseases, such as arthritis.
Using state-of-the-art phosphoproteomics, flow cytometry and genetic models the student will investigate how the PIM kinases regulate immune cell activation in response to IL-15. The student will use both animal models and human intestinal immune cells to test the efficacy and importance of blocking these enzymes in controlling immune inflammation. They will evaluate PIM kinase expression in human patient samples. Importantly, the student will have the opportunity to work closely with a world-leading pharmaceutical company, Astra Zeneca, to improve drug efficiency and design, and get a 3-month placement at Astra Zeneca Cambridge. This is an exciting opportunity to explore a promising new therapeutic avenue for IL-15 mediated inflammatory diseases, while gaining fundamental insights into mechanisms and biology of the understudied PIM kinase family.
The project will be carried out at the The MRC Protein Phosphorylation and Ubiquitylation Unit, a world-famous centre for the study of cell signaling and how disruption to signaling pathways causes human disease.
ENQUIRIES:
Enquiries should be sent by email to Dr Mahima Swamy:
[Email Address Removed]
APPLICATIONS:
Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK, in biological sciences, ideally with some research experience.
Applicants should send a CV, the contact details of 2 or 3 referees (including email addresses) and a covering letter, explaining why you have chosen to apply for this particular project, by email to Dr Mahima Swamy:
[Email Address Removed]
Please note, your application may be shared with the funders of this PhD Studentship, Medical Research Scotland and AstraZeneca UL Ltd.
Interviews are expected to take place 3-4 weeks after the closing date for applications. In light of the current coronavirus situation, interviews may be conducted by video conference.
It is anticipated that the PhD Studentship will start 1 October 2021.
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