LICAMM Vascular Smooth Muscle Cell Orai1 and vascular disease

Orai1 is a highly selective calcium permeable ion channel which is expressed in vascular smooth muscle cells (VSMCs), the main cellular component of the vessel wall. It is already established as an important driver of pathological vascular remodeling in cardiovascular diseases and a potential novel therapeutic target (1). We have previously shown that inhibition of Orai1 protects the heart from adverse remodeling in the context of pressure overload (2). In our laboratory we have developed VSMC conditional Orai1 knockout mice. In this project we will use these mice and aligned studies in wild-type mice using our novel Orai1 small-molecule inhibitors to explore the role of Orai1 in atherosclerosis and neo-intimal hyperplasia (the driving force behind surgical or endovascular treatment failure) to model human disease with and without metabolic stress. The study will use both dietary and surgical disease models of vascular disease, transgenic mice and CT angiography in our British Heart Foundation funded pre-clinical imaging facility.

<h5 style="margin-bottom: 13px;">References</h5> <ol> <li>Shawer H, Norman K, Cheng CW, Foster R, Beech DJ, Bailey MA. ORAI1 Ca 2+ Channel as a Therapeutic Target in Pathological Vascular Remodelling. Front Cell Dev Biol. 2021 Apr 6;9:653812. doi: 10.3389/fcell.2021.653812.</li> <li>Bartoli F, Bailey MA, Rode B, Mateo P, Antigny F, Bedouet K, Gerbaud P, Gosain R, Plante J, Norman K, Gomez S, Lefebvre F, Rucker-Martin C, Ainscough JFX, Kearney MT, Bruns AF, Shi J, Appleby HL, Young RS, Shawer HM, Debant M, Gomez AM, Beech DJ, Foster R, Benitah JP, Sabourin J. Orai1 Channel Inhibition Preserves Left Ventricular Systolic Function and Normal Ca2+ Handling After Pressure Overload. Circulation. 2020 Jan 21;141(3):199-216. doi: 10.1161/CIRCULATIONAHA.118.038891.</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 area is desirable but not essential.

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: • British Council IELTS - score of 6.5 overall, with no element less than 6.0 • TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

<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>