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Switching off immunity in health and disease

PGR-P-78

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
Professor Graham Cook, Dr Robert Salmond, Dr Laura Matthews
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Medical Research at St James's
<h2 class="heading hide-accessible">Summary</h2>

Immune activation, for example during an infection, is followed by feedback inhibition which dampens down the response. A failure to activate immunity results in overwhelming infection; equally, an inability to halt the immune response results in pathological inflammation and sometimes autoimmunity. We are interested in the molecular mechanisms used by the immune system to halt the response. In particular, we are interested in the action of immunosuppressive cytokines (such as TGF-beta and IL-10) and how anti-inflammatory drugs (such as steroids) mimic the action of these cytokines. The project will use molecular and cellular techniques to define the signalling pathways used by immunosuppressive molecules to regulate immunity and how these pathways are modulated in human cancer and inflammation. The project will focus on the action of inhibitory molecules on natural killer (NK) cells and cytotoxic T cells, comparing cytokines and drugs for their ability to regulate immune activity. Tumours often exploit these pathways to inhibit anti-tumour immunity. Defining the mechanisms operating in cancer will enable the design of therapeutic strategies that will help to restore anti-tumor immunity.

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

<h3>References</h3> <ol> <li>Holmes TD, Wilson EB, Black EVI, Benest AV, Vaz C, Tan B, Tanavde VM, Cook GP (2014) Licensed human natural killer cells aid dendritic cell maturation via TNFSF14/LIGHT.&nbsp;<em>Proc Natl Acad Sci USA </em>111(52):E5688-96.</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> <em>Nat. Commun.</em> 8(1):1343.</li> <li>Wilson EB, El-Jawhari JJ, Neilson AL, Hall GD, Melcher AA, Meade JL and Cook GP (2011) Human tumour immune evasion via TGF-b blocks NK cell activation but not survival allowing therapeutic restoration of anti-tumour activity. <em>PLoS One</em> 6:e22842.</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&nbsp;<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>