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
Blank
Job description
Immunogenic protein secretion as a regulator of cell death in cancer BackgroundA 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 QuestionThis 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 gainedThe 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.