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Black Leaders in Cancer PhD Scholarship: Immunogenic protein secretion as a regulator of cancer cell death

Posted on 14 November 2024

Job type: phd

Location: Cancer Research UK Scotland Institute, Glasgow

Closing Date: 25 November 2024

Black Leaders in Cancer PhD studentship

About the programme

As part of Cancer Research UK’s commitment to Equality, Diversity and Inclusion in Research, they have developed this programme in consultation with the research community and in close collaboration with expert partners, Black in Cancer and the Windsor Fellowship.

This programme provides a unique opportunity for students from Black heritage backgrounds to pursue a 4-year fully-funded PhD in cancer research. Those students will benefit from being part of our CRUK Scotland Institute programme and from a comprehensive programme of mentoring, career support, leadership training and networking led by the Windsor Fellowship and Black in Cancer. By helping candidates from Black heritage backgrounds build their career in cancer research-related fields, this exciting programme is designed to make an immediate and tangible impact on the diversity of the research workforce.

Immunogenic protein secretion as a regulator of cell death in cancer

Prof David Bryant & Prof Stephen Tait

Labs: Epithelial Polarity & Mitochondria and Cell DeathMitochondria and Cell Death
Duration: 4 years, starting October 2025
Closing Date: Monday 25 November 2024
Interviews for this position will take place January/February 2025

 

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.

 

For questions regarding the application process, PhD programme/studentships at the CRUK Scotland Institute or any other queries, please contact phdstudentships@beatson.gla.ac.uk.

 

Closing date: Monday 25 November 2024

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

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