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Metabolic regulation of anti-tumour T cell immunity

PGR-P-73

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
International (open to all nationalities, including the UK)
Funding
Non-funded
Additional supervisors
Dr Robert Salmond
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Medical Research at St James's
<h2 class="heading hide-accessible">Summary</h2>

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 &ldquo;self&rdquo; 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.

<h2 class="heading hide-accessible">Full description</h2>

<p>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.</p> <h3>References:</h3> <ol> <li>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.</li> <li>Brownlie RJ, Garcia C, Ravasz M, Zehn D, Salmond RJ, Zamoyska R. 2017. <a href="https://www.ncbi.nlm.nih.gov/pubmed/29116089">Resistance to TGF&beta; suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22.</a> Nat. Commun. 8(1):1343.</li> </ol>

<h2 class="heading">How to apply</h2>

<p>Applications can be made at any time. To apply for this project applicants should complete a<a href="https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form"> Faculty Application Form</a> 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 <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>.</p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>If you have already applied for other projects using the Faculty Application Form this academic session you do not need to complete this form again. Instead you should email <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a> to inform us you would like to be considered for this project.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

<h2 class="heading heading--sm">English language requirements</h2>

Applicants 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 of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: &acirc;&euro;&cent; British Council IELTS - score of 6.5 overall, with no element less than 6.0 &acirc;&euro;&cent; 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.

<h2 class="heading">Contact details</h2>

<p>For further information please contact the Graduate School Office<br /> e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a> t: +44 (0)113 343 8221.</p>