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

Dr Seth Coffelt and Dr Kevin Myant

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Labs:
Coffelt Lab
Myant Lab
Duration: 4 years from September 2022
Closing Date: 27th May 2022

About us

Applications are invited from outstanding candidates to join a Cancer Research UK funded PhD programme at the Beatson Institute. These are funded by the Cancer Research UK Scotland Centre, a joint initiative between Edinburgh and Glasgow which brings together cancer scientists and clinicians from across the Universities of Edinburgh and Glasgow, delivering outstanding cancer research and improved patient care. The Cancer Research UK PhD programme is integrated into the research activities of the Centre with over 80 principal investigators contributing to this cross-disciplinary programme spanning from fundamental science to translational research. Research projects benefit from state-of-the art facilities for genomics, mass spectrometry, advanced microscopy, single cell technologies, and from advanced computational and informatics capabilities.

Project description

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 γδ T cells function differently in inflammatory-driven tumours as compared with sporadic tumours. This hypothesis will be tested in the following specific aims:

1. Characterize 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.

Application procedure

Up to 3 studentships are available to start in September 2022 for outstanding applicants with a stipend of £19,000 p/a. These are funded by the CRUK Scotland Centre, a joint initiative between Edinburgh and Glasgow. Successful students 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.

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