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Cancer: Functional characterization of the tumour suppressor gene CSMD1 in breast cancer

PGR-P-53

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
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Medical Research at St James's
<h2 class="heading hide-accessible">Summary</h2>

CUB and Sushi multiple domains protein 1 (CSMD1) maps to 8p23, a region deleted in many cancers including breast cancer. Our previous work has established that CSMD1 is an independent prognostic marker in ductal breast cancer, with reduced expression associated with high tumour grade and poor survival. CSMD1&rsquo;s function is unknown; however, our data suggests that CSMD1 is involved in a signaling cascade regulating a wide range of cell processes involved in cancer development.

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

<p style="margin-left: 2.85pt;">We have already generated shRNA and CRISPR cell lines with reduced CSMD1 expression to investigate the function of CSMD1. Analysis of these cell lines has shown that suppression of CSMD1 expression disrupts cell morphology, in an effect resembling the epithelial-mesenchymal transition (EMT), increases cell proliferation, and enhances cell migration and cell invasion. We have also established an MCF10A three-dimensional culture model with reduced CSMD1 expression which revealed that loss of CSMD1 expression resulted in the development of larger and more poorly differentiated breast ductal structures2. &nbsp;In addition, we have also recently developed an in vivo model with reduced CSMD1 expression. Our aims will be to investigate the role of CSMD1 in metastasis which is the primary cause of cancer-associated mortality. We will study the mechanisms behind the function of CSMD1 in EMT, tumour migration and invasion using our 3D culture and in vivo models.<br /> &nbsp;<br /> You student will gain experience of a broad range of molecular and cell biology laboratory techniques including CRISPR, cell culture of 3D models, confocal microscopy, live cell imaging, Gene expression analysis, RT-PCR, pathway analysis, Western blotting, in vivo work, migration and cell invasion assays, immunohistochemistry and immunofluorescence.</p> <h3 style="margin-left: 2.85pt;">References:</h3> <ul> <li> <p style="margin-left: 2.85pt;">Kamal M, Shaaban AM, Zhang L, Walker C, Gray S, Thakker N, Toomes C, Speirs V, Bell SM. Loss of CSMD1 expression is associated with high tumour grade and poor survival in invasive ductal breast carcinoma. <em>Breast Cancer Res Treat </em>(2010) 121(3):555-63.</p> </li> <li> <p style="margin-left: 2.85pt;">Kamal M, Holliday DL, Morrison EE, Speirs V, Toomes C, Bell SM. Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion. Oncology Reports (2017) Jul;38(1):283-292.</p> </li> </ul> <p style="margin-left: 2.85pt;">This project is part of the <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 style="margin-left: 2.85pt;"><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>

<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>

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

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject. 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 reguarding the bespoke taught first year of the PhD programme and research projects can be made by contacting LIMRPhD@leeds.ac.uk.</p> <p>For further information about the application process&nbsp;please contact the Graduate School Office&nbsp;e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>, t: +44 (0)113 343 8221</p>


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