Black Leaders in Cancer PhD Programme (David Bryant & Stephen Tait)

Cancer Research UK
November 25, 2024
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Offerd Salary:£21,000
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Contract Type:Other
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Job details

Job title

Black Leaders in Cancer PhD Programme (David Bryant & Stephen Tait)

Job reference

REQ00373

Date posted

24/10/2024

Application closing date

25/11/2024

Location

Glasgow

Salary

Stipend - £21,000 per annum

Package

All tuition fees will be covered

Contractual hours

Blank

Basis

Blank

Job category/type

PhD Students

Attachments

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Job description

Immunogenic protein secretion as a regulator of cell death in cancer Background

A major goal of cancer therapy is to selectively kill cancer cells while sparing normal tissue. The way in which cell death is triggered in vivo is fundamental to a clinical response. Cell death that engages anti-tumour immunity, so called immunogenic cell death, can enable complete eradication of cancer. How cell death can be manipulated to become immunogenic remains a key question. Mitochondria are major regulators of cell survival and death and do so in part by regulation of pro- or anti-inflammatory mediators, depending on the cellular context. The secretion of such immune-modulatory proteins is therefore a key event in the live or die decision for a cancer cell. The ARF family of small GTPases are the key machinery that control protein secretion and have emerged as therapeutic targets to trigger immunological response in tumours. ARF GTPases have also emerged as fundamental regulators of mitochondrial homeostasis. Unravelling how ARF GTPases can be targeted to control immunogenic cell death, and how these interfaces with the key regulator of cell death – the mitochondria – may provide improved therapeutic options in cancer.

Research Question

This project examines the cellular mechanisms by which ARF GTPases control mitochondrial homeostasis, thereby influencing whether immunological cell death can occur. The project will involve genomic engineering of cancer cells in vitro to unravel the interplay between ARF GTPases, mitochondria, cell death and immunogenic protein secretion. This will be examined in model systems of cancer than are examined both in vitro and upon transplantation in vivo in immune-competent hosts to determine the key requirement for immune- mediated anti-cancer therapies.

Skills/Techniques that will be gained

The candidate will be equally appointed and supervised across two neighbouring laboratories, David Bryant (ARF GTPases and tumourigenesis) and Stephen Tait (immunogenic cell death and mitochondria). The student will receive outstanding training in the cell biology of cancer, including cell death and immune signalling mechanisms. Key techniques gained include mouse models of cancer, transplantation models of cancer, genetic editing (CRISPR, viral methodology) and molecular analysis of cancer cells, 3-Dimensional culture techniques of organoids, and advanced live imaging and analysis. In addition, the project will explore drug repurposing and combination therapies (e.g. immunotherapy) to identify therapeutic interventions against tumour formation and metastasis.

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