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Cancer: 3D model of the brain tumour perivascular niche: developing new approaches to target brain tumours

PGR-P-209

Key facts

Type of research degree
4 year PhD
Application deadline
Ongoing deadline
Country eligibility
International (outside UK)
Funding
Non-funded
Supervisors
Dr Sandra Bell and Dr Georgia Mavria
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Medical Research at St James's
<h2 class="heading hide-accessible">Summary</h2>

Aggressive brain tumours have dismal outcomes. Patients with glioblastoma multiforme, or brain metastases arising from tumours in other part of the body such as melanoma and breast cancer, have a median survival of only 14 months when treated with surgery followed by radiation and chemotherapy. This is due to resistance to treatment by cancer stem-like cells (CSCs), cells that have the ability to self-renew and reignite tumour growth following therapy. CSCs preferentially associate with the tumour perivascular niche, and abundance of the niche correlates positively with tumour grade and negatively with patient survival (1, 2). The brain microvasculature and other supportive cells within the niche, including immune cells, pericytes and astrocytes, provide a protective role for CSCs through complex paracrine interactions (1). Understanding these interactions will lead to discovery of new targets, and new and better therapies for brain tumours.

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

<p><strong>Objectives:&nbsp;</strong>You will use the laboratory&rsquo;s extensive expertise in 3-dimensional organotypic models (3), data obtained from detailed analysis of glioblastoma patient samples, and available patient-derived CSC lines to&nbsp;<em>i)</em>&nbsp;develop a model that recapitulates the key characteristics of the brain tumour perivascular niche,&nbsp;<em>ii)</em>&nbsp;evaluate the response to therapy of CSCs situated within the niche&rsquo;s protective environment and&nbsp;<em>iii)</em>&nbsp;identify new molecules that promote the growth of CSCs within the niche, and evaluate response to therapy following knockdown their expression.</p> <p>The project provides an excellent opportunity to train in state-of-the-art cell and molecular biology techniques working within an excellent multidisciplinary environment with medical researchers and clinicians.</p> <p><strong>References:</strong></p> <p>1. Charles, N., Holland, E. (2010) The perivascular niche microenvironment in brain tumour progression. Cell cycle 9:3012-21.</p> <p>2. Ochs, K., et al (2013). Immature mesenchymal stem cell-like pericytes as mediators of immunosuppression in human malignant glioma. J Neuroimmunol. SO165-5728:253-61.</p> <p>3. Abraham S, Scarcia M, Bagshaw RD, McMahon K, Grant G, Harvey T, Yeo M, Esteves FO, Thygesen HH, Jones PF, Speirs V, Hanby AM, Selby PJ, Lorger M, Dear TN, Pawson T, Marshall CJ and Mavria G (2015). A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis Nat Commun. 6, 7286.</p> <p>This project is available as part of the&nbsp;<a href="https://medicinehealth.leeds.ac.uk/leeds-institute-research-st-james/doc/international-phd-academy-medical-research">International PhD Academy: Medical Research</a></p> <p><strong>In line with the bespoke nature of our International PhD Academy a modified PhD project can be proposed dependent on students interests and background.</strong></p> <p>&nbsp;</p>

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

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. To apply for this project applicants should complete an <a href="http://www.leeds.ac.uk/info/130206/applying/91/applying_for_research_degrees">online application form</a> and submit this&nbsp;alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates. Please make it clear in the research information section that you are applying for the International PhD Academy: Medical Research, as well as the title of the project you wish to be considered for.</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 English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p>&nbsp;</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 7.0 overall, with no element less than 6.5 &acirc;&euro;&cent; TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.

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

<p>Informal enquires about regarding the bespoke taught first year of the PhD programme and research projects can be made by contacting LIMRPhD@leeds.ac.uk.</p> <p>Enquiries regarding the application process should be directed to the Faculty of Medicine and Health Graduate School&nbsp;Office&nbsp;e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>,&nbsp;t: +44 (0)113 343 8221.</p>


<h3 class="heading heading--sm">Linked research areas</h3>