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Unravelling the unusual secretory pathway of blood clotting factor XIII-A.

PGR-P-225

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Key facts

Type of research degree
4 year PhD
Application deadline
Ongoing deadline
Country eligibility
International (outside UK)
Funding
Non-funded
Additional supervisors
Richard Pease, Paul Cordell
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Cardiovascular and Metabolic Medicine
<h2 class="heading hide-accessible">Summary</h2>

Clotting factor XIII-A is a member of the transglutaminase family of enzymes. Transglutaminases introduce covalent cross-links between other proteins, and in the case of FXIII-A, it cross-links the chains of fibrinogen to one another to stabilize blood clots. Transglutaminases are unusual in that, while they can be secreted from cells, they lack the signals required to direct them to the ER-Golgi pathway. Thus, they are among a small group of proteins that undergo unconventional secretion.

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

<p>Recent studies have begun to clarify the pathways by which a few other unconventionally secreted proteins are released from cells, and we intend to apply the approaches that have emerged to understand the secretion of FXIII-A. Our recent studies have suggested that vascular macrophages secrete FXIII-A into the blood-stream and we will concentrate on isolating these cells, and establishing in vitro culture models under which cells adopt the characteristics of vascular macrophages.</p> <p><strong>References:</strong></p> <p>Association of coagulation factor XIII-A with Golgi proteins within monocyte-macrophages: implications for subcellular trafficking and secretion. Cordell PA et al (2010); Blood. 115 2674-81.</p> <p>Cre/lox Studies Identify Resident Macrophages as the Major Source of Circulating Coagulation Factor XIII- A Beckers CML et al (2017);, Arteriosclerosis, Thrombosis, and Vascular Biology. 37 1494-1502</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. You should complete an <a href="https://medicinehealth.leeds.ac.uk/faculty-graduate-school/doc/apply-2">online application form</a> and attach the following documentation to support your application.&nbsp;</p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks (or marks so far if still studying)</li> <li>Evidence that you meet the programme&rsquo;s minimum English language requirements (if applicable, see requirement below)</li> <li>Evidence of funding to support your studies</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Cardiovascular and Metabolic Disease as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul>

<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 minimum requirements for this programme in IELTS and TOEFL tests are: &bull; British Council IELTS - score of 7.0 overall, with no element less than 6.5 &bull; 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>For further information please contact the Faculty Graduate School<br /> e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p>


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