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  Understanding the pro- and anti-tumour functions of IFNγ-producing γδ T cells


   College of Medical, Veterinary and Life Sciences

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  Dr Seth Coffelt  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

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γδ T cells are a rare population of T cell receptor-expressing cells that function like innate immune cells.γδ T cells consist of several different subtypes that can promote or prevent cancer progression, depending on the cytokines and cytotoxic molecules they express. IFNγ-producing γδ T cells are considered anti-tumorigenic cells, and the Coffelt lab has shown that these cells recognize and directly kill breast cancer cells. Conversely, the Myant lab has found that IFNγ-producing γδ T cells infiltrate tumours in mouse models of colitis associated colorectal cancer, where they promote tumour growth. This pro-tumorigenic role of IFNγ-producing γδ T cells is perpetuated by the loss of DOCK2, an activator of the actin remodelling molecule, Rac. However, how DOCK2 influences the behaviour of IFNγ-producing γδ T cells and the context in which IFNγ-producing γδ T cells can mediate pro- or anti-tumour functions remains unknown. In this project, we will explore when and where IFNγ-producing γδ T cells are tumour suppressive versus tumour stimulatory. We hypothesize that IFNγ-producing γδT cells function differently in inflammatory-driven tumours as compared with sporadic tumours. This hypothesis will be tested in the following specific aims:

1. Characterise the phenotype of IFNγ-producing γδ T cells in inflammation-driven and sporadic mouse models of colon and pancreatic cancer

2. Determine how DOCK2 impacts STAT1/IRF/T-BET/IFNγ signalling in γδ T cells

3. Determine the mechanism by which IFNγ-producing γδ T cells drive cancer progression.

The student will work with mouse models of cancer. A number of techniques will be mastered including flow cytometry, western blot, PCR, T cell culture, and organoid culture.

Application procedure

The project is part of a competition-based recruitment call by the CRUK Scotland Centre, a joint initiative between Edinburgh and Glasgow. Successful students will start in September 2022 and will be registered for their degree in either Glasgow or Edinburgh, depending on the project they apply for.

We are looking for students with a very good degree in a Life Sciences subject and an aptitude for experimental work, who are also highly committed to pursuing a PhD and a career in cancer research. You should hold at least an upper second-class degree in a relevant subject and comply with English language requirements.

All applications will be administered centrally via the University of Edinburgh, please apply on the link below - this includes Glasgow-based projects with Glasgow-based supervisors: https://www.star.euclid.ed.ac.uk/public/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=PRPHDCECRC1F&code2=0020

Closing date: 27 May 2022

Interviews are expected to be held week beginning 27 June.

Applications are open to all individuals irrespective of nationality or country of residence.

Biological Sciences (4)

Funding Notes

Stipend of £19,000 p/a, for 4 years funded by the CRUK Scotland Centre, plus matriculation fees and consumables budget. Must have at least an upper second-class degree (or equivalent) in a Life Sciences subject and comply with English language requirements.