MRes - Investigating the cellular mechanisms that cause cardiovascular complications in Duchenne Muscular Dystrophy
Supervisors: Dr Christina Warboys & Professor Richard Piercy
Department: Comparative Biomedical Sciences & Clinical Science and Services
Project Detail:
Duchenne Muscular Dystrophy (DMD), a universally-fatal, X-linked muscle wasting disease is caused by mutations in the dystrophin gene. Whilst characterised by progressive muscle weakness, the leading cause of death is cardiovascular disease. Currently however, the cardiovascular pathophysiology is very poorly understood, hampering treatment discovery. This project will address an under-evaluated, but potentially critical component of this disorder that we believe contributes to disease development.
Endothelial cells that line blood vessels regulate vascular tone and blood pressure. Endothelial dysfunction is a key driver of many cardiovascular diseases and likely plays a role in DMD by increasing systemic vascular resistance and thereby, the heart’s workload. Endothelial cells are mechanosensitive and their function is finely regulated by shear stress (exerted by blood flowing across the cell surface). Dystrophin is expressed within endothelial cells and absence of dystrophin impairs flow-mediated vasodilation, a shear stress-mediated process.
We hypothesise that dystrophin’s absence in endothelial cells in DMD impairs mechanotransduction and promotes endothelial dysfunction. The aim of this project is to determine dystrophin’s role in endothelial mechanotransduction and thereby, to explain early features of DMD’s developing cardiovascular phenotype.
This project will use cultured dystrophin-deficient and control endothelial cells (primary and IPSC-derived) in a well characterised cell-based system. Using molecular and cellular biology techniques, including qRT-PCR, in situ hybridisation and immunohistochemistry, we will investigate whether the expression of dystrophin is regulated by shear stress and will explore functional deficits associated with its absence. This work will provide novel insights on the role of a critical protein involved in a fatal neuromuscular disorder, and might suggest novel approaches to treatments.
References:
- Schultz, T. et al. Cardiovascular Disease in Duchenne Muscular Dystrophy. JACC Basic Transl. Sci. 7, 608–625 (2022).
- Loufrani, L. et al. Flow (Shear Stress)–Induced Endothelium-Dependent Dilation Is Altered in Mice Lacking the Gene Encoding for Dystrophin. Circulation 103, 864–870 (2001)
- Warboys, C. M et al. Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method. Atherosclerosis 285, 170–177 (2019).
Requirements
Essential
- Must meet our standard MRes entry requirements. No need to be a vet
Desirable
- Experience with cell culture
- Experience with cell or molecular biology techniques
This project can be taken full-time commencing in October 2026, based at RVC's Camden campus.
This project will utilise primary cells derived from research animals, and human IPSCs with appropriate ethical approval.
The project will not involve any direct live animal research.
Funding:
Fully funded project: The project costs and “Home” tuition fees are covered by funding from the supervisor.
The student will receive a stipend/will be expected to cover their living expenses. International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees.
Please note that EU/EEA and Swiss national students may no longer be eligible for the “Home” rate of tuition fees, dependent on personal circumstances (including immigration status and residence history in the UK) and UK government rules which are currently being developed. For up-to-date information on fees for EU/EEA and Swiss national students following Brexit please see our fees and funding page.
How to Apply
Deadline: 8th May 2026
For more information on the application process and English Language requirements see How to Apply.
Interviews will take place remotely (Teams, Zoom etc) within 4 weeks of the closing date.We welcome informal enquiries - these should be directed to cwarboys@rvc.ac.uk
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