LICAMM The role of Rab46 in cardiovascular disease

Endothelial cells line the blood vessels and play a central role in vascular function. Weibel Palade bodies (WPBs) are specialized storage vesicles found specifically in endothelial cells (1). These vesicles contain a pool of readily made cargo that, upon release, control vascular events such as haemostasis, inflammation, angiogenesis and vascular tone. Inappropriate release of WPB cargo into the blood vessel lumen results in the pro-inflammatory and pro-thrombotic environment associated with cardiovascular disease. My research involves understanding the mechanisms underlying the release of WPB cargo and how these become perturbed in cardiovascular disease.

<p>Recently, we described a novel Rab GTPase (Rab46) in endothelial cells that has GTPase and Ca2+ binding activities and is located on WPBs (2)(2). Thereby, this research project involves a range of techniques including;- cell culture, siRNA transfection, calcium imaging, biochemistry, MRI and confocal microscopy, to address the role of Rab46 in WPB trafficking and endothelial cell secretion. In addition, we will investigate how mutations in this protein may contribute to cardiovascular diseases and explore the association of Rab46 with other inflammatory diseases using data from the UK Biobank.</p> <p><strong>References:</strong></p> <p>Weibel, E. R. (2012) Fifty years of Weibel-Palade bodies: the discovery and early history of an enigmatic organelle of endothelial cells. Journal of thrombosis and haemostasis : JTH 10, 979-984</p> <p>Wilson, L. A., McKeown, L., Tumova, S., Li, J., and Beech, D. J. (2015) Expression of a long variant of CRACR2A that belongs to the Rab GTPase protein family in endothelial cells. Biochemical and biophysical research communications 456, 398-402</p>

<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. For entry requirements for all other research degrees we offer, please contact us.

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 • 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.

<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>