LICAMM Investigating the contribution of fibrinogen crosslinking to platelet production

Platelets, small cells in the blood, are the master regulators of haemostasis, controlling the balance between blood clotting and bleeding. Platelets are produced by megakaryocytes through a tightly regulated maturation process called thrombopoiesis which controls circulating platelet number and function. Understanding this process is crucial to maintaining platelet number and the haemostatic balance.

<p>Megakaryocytes are specialised cells in the bone marrow that are derived from the differentiation of haematopoietic stem cells. To facilitate platelet production, megakaryocytes mature and then migrate towards the blood vessels. Here they extend proplatelet protrusions through the endothelial barrier and into the blood stream and release platelets through a process involving membrane-blebbing into the circulation. This process is tightly regulated by the bone marrow microenvironment and disruptions to this environment leads to alterations in platelet production and biology^[1].  Several studies have identified the bone marrow extracellular matrix (ECM) to be a key regulator of these process.</p> <p>We are interested in how the ECM component fibrinogen which can be crosslinked to fibrin is involved in platelet production^[2]. However, very little is known regarding how the structure and mechanical properties of fibrin(ogen) facilitates these processes.</p> <p>This project aims to: </p> <ol> <li>Determine the contribution of the fibrin(ogen) to the bone marrow microenvironment megakaryocyte biology and platelet production. </li> <li>Characterise the role of fibrinogen crosslinking in the process of platelet production.</li> </ol> <h5>References</h5> <ol> <li>Malara, A., et al., Megakaryocytes contribute to the bone marrow-matrix environment by expressing fibronectin, type IV collagen, and laminin. Stem Cells, 2014. 32(4): p. 926-37.</li> <li>Duval, C., et al., Roles of fibrin alpha- and gamma-chain specific cross-linking by FXIIIa in fibrin structure and function. Thromb Haemost, 2014. 111(5): p. 842-50.</li> </ol>

<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. </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’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 Medicine, Health & Human Disease as your planned programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul>

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.

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: • British Council IELTS - score of 7.0 overall, with no element less than 6.5 • Internet Based TOEFL - overall score of 95 with not less than 22 in listening, 22 in reading, 24 in speaking and 22 in writing.

<p>For further information please contact the Faculty Admissions Team:<br /> e:<a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p>