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(MCRC Non-Clinical) Exploiting ERK5-signalling to modify T-cell behaviour during tumour progression and radiotherapy response: a new immunotherapy approach?

Project Description

Project summary:
ERK5 is a signalling protein that enables cells to transduce extracellular signals into responses. It is expressed in all tissues and is up-regulated in tumours. Up-regulated EKR5-signalling in patient samples (biopsies) correlates with poorer overall outcome and resistance to chemotherapy. Exactly how ERK5 signalling regulates cancer progression and therapy response is not known. We have novel findings (unpublished) showing that the ERK5-pathway regulates T-cell behaviour in skin cancers, but nothing is known about the nature of this interaction. T-cells are cells of the immune system that, in the context of cancer, can attack tumours (so called anti-tumour responses), causing a reduction in tumour size or even elimination of the tumour. However, frequently the tumour “switches off” anti-tumour T-cell responses. As a result, immunotherapy drugs have been developed that switch anti-tumour T-cell responses back on and are commonly used to treat cancer patients.
However, a large sub-set of patients don’t respond to current immunotherapy approaches. Therefore, there is an urgent need to i) better understand T-cell biology in cancer to make current therapies work better and ii) find new methods to modulate T-cell behaviour, which would form the basis of future immunotherapies. Thus, it is essential we characterise this newly revealed interaction between ERK5 and T-cells to understand how we can exploit it for therapeutic gain in patients.
This project will use a patient-mimetic skin cancer model to characterise the mechanisms underpinning ERK5’s modulation of T-cell behaviour. We will determine if modifying ERK5 signalling augments response of skin tumours to radiotherapy. In parallel, we will investigate the relationship between ERK5 and T-cell biology in SCC patients, of which nothing is known. Data from this project will be used to i) develop better ways to track cancer progression in patients (biomarkers) and ii) reveal novel targets for future drug development.

Entry Requirements:
Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage. Applications from all nationalities are welcome.

Funding Notes

The Studentship will cover an annual stipend (currently at £19,000 per annum), running expenses and PhD tuition fees at UK/EU rates. Where international student fees are payable, please provide evidence within your application of how the shortfall will be covered (approximately £19,000 per annum).

The length of this project will be FOUR YEARS.

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