Metabolic regulation of anti-tumour T cell immunity

Project description

The induction of effective immune responses to tumours can provide long-lasting protection from cancer. In this regard, cytotoxic CD8+ T cells can suppress tumour growth by directly killing cancer cells and also by producing inflammatory cytokines. However, in many individuals the T cell response to cancer is ineffective. Several factors underlie the failure to mount protective immunity to cancer. Firstly, T cell responses can be suppressed by the inhibitory tumour environment. Secondly, tumour antigens are often perceived by the immune system as being identical to normal “self” tissue, and therefore a T cell response is not strongly induced. Therefore, it is clear that in order to improve patient outcomes and therapeutic opportunities in cancer, we need to understand how immune responses to tumours are regulated.

The aim of this project is to investigate how T cells integrate antigenic, cytokine and environmental signals, particularly in the context of the tumour microenvironment. A key approach will be to determine how fundamental cellular metabolic pathways regulate T cell activation and effector function. This will be tested using in vitro and ex vivo analyses of transgenic mouse T cells. In vitro cellular immunology and biochemical techniques will complement in vivo mouse studies. A further aim to be to understand how these pathways are regulated in human T cells. This project is suitable for students with a strong background and interest in immunology, biochemistry, molecular biology or cell biology.

References:

1. Salmond RJ, Brownlie RJ, Morrison VL, Zamoyska R. 2014. The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals. Nat. Immunol. 15(9):875-883.

2. Brownlie RJ, Garcia C, Ravasz M, Zehn D, Salmond RJ, Zamoyska R. 2017. Resistance to TGFβ suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22. Nat. Commun. 8(1):1343.

Entry requirements

This project is available immediately to both Home/EU rate applicants and International applicants who are able to self-fund their studies. Students must be able to provide the appropriate level of fees based on their fee status plus laboratory consumables costs per year. This is in addition to the provision of personal living expenses.

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject.

Candidates whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study, the Faculty minimum requirements are:

• British Council IELTS - score of 6.5 overall, with no element less than 6.0
• TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

Applicants with sufficient funding must still undergo formal interview

How to apply

Applications can be made at any time. Potential applicants are welcome to contact Dr Robert Salmond with informal enquiries about this research project.

To formally apply for this project applicants should complete a Faculty Scholarship Application form and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School.

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly by email

If you have already applied for other scholarships using the Faculty Scholarship Application form you do not need to complete this form again. Instead you should email toinform us you would like to be considered for this scholarship project.