LICAMM Orai1 SNPs and Peripheral Arterial Disease severity using CT angiography imaging features

Key facts

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 remodelling in cardiovascular diseases and a potential novel therapeutic target (1). We have previously shown that inhibition of Orai1 protects the heart from adverse remodelling in the context of pressure overload (2).

Peripheral arterial disease (PAD) describes atherosclerosis in the peripheral (typically leg) arteries. It presents as pain on walking (claudication) and in severe cases, chronic limb threatening ischaemia with a high risk of limb loss without emergency surgery. Most patients are claudicants and their main risk is of adverse cardiovascular events such as heart attack and stroke.

Using UK Biobank we have identified a mutant of Orai1 that is associated with peripheral arterial disease, generalized atherosclerosis and lipid metabolism. In this study we will genotype patients with PAD for this Orai1 small nucleotide polymorphism (SNP) and use their CT angiographic images to investigate if the presence of this SNP affects disease severity (plaque burden, extent of disease, classification of plaque). There will be the opportunity to delve into the images using artificial intelligence neural networks to reveal additional data.

References

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.

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.

Please note these are not standalone projects and applicants must apply to the PhD academy directly.

Applications can be made at any time. You should complete an online application form and attach the following documentation to support your application.

a full academic CV

degree certificate and transcripts of marks (or marks so far if still studying)

Evidence that you meet the programme’s minimum English language requirements (if applicable, see requirement below)

Evidence of funding to support your studies

To help us identify that you are applying for this project please ensure you provide the following information on your application form;

Select PhD in Medicine, Health & Human Disease as your planned programme of study

Give the full project title and name the supervisors listed in this advert

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 minimum requirements for this programme in IELTS are: British Council IELTS - score of 6.5 overall, with no element less than 6.0.

This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs.

Enquiries regarding the application process should be directed to the Faculty of Medicine and FMH admissions e: fmhpgradmissions@leeds.ac.uk

• Type of research degree: 4 year PhD
• Application deadline: Tuesday 31 August 2027
• Country eligibility: International (outside UK)
• Funding: Non-funded
• Supervisors: Dr Marc Bailey
• Additional supervisors: Mr Patrick Coughlin, Professor Andrew Scarsbrook, Professor David Beech
• Schools: School of Medicine
• Research groups/institutes: Leeds Institute of Cardiovascular and Metabolic Medicine

Research areas