Supervisors: Prof Richard Piercy and Dr Androniki Psifidi

Department: Clinical Science and Services

Project Details

Duchenne muscular dystrophy (DMD) is an invariably fatal, X-linked muscle wasting disease affecting 1 in 5000 boys. Lack of dystrophin protein results in myofibre degeneration, leading to infiltration or replacement of muscle with adipose or connective tissue (fibrosis). Progressive skeletal muscle dysfunction results in loss of ambulation by adolescence and ultimately, respiratory and cardiac muscle failure. Advances in supportive management and the use of palliative steroid treatment has increased longevity for DMD patients but there is still no cure. Canine models with the veterinary equivalent of DMD are useful for evaluation of sophisticated treatments. One in particular, the DE50-MD model, is used for evaluation of gene therapies, gene editing and exon skipping approaches that could be applied to both veterinary and human patients in the future. However, inherent phenotypic severity variation between dogs can compromise the robustness of treatment trials and increases animal use with associated ethical implications. 

Integrating genetics, genomics and other omics analyses such as Genome Wide Association Studies, low pass sequencing with imputation, whole genome sequencing and RNAseq, the student will test the hypothesis that there are genetic loci that alter the phenotype in DMD-affected animals. Working with other students and post docs, there is opportunity to learn a range of sophisticated, cutting-edge genomic methods of relevance to veterinary and human genetics. This project involves pre-existing samples collected from a canine model of Duchenne Muscular Dystrophy. The student will be trained in both wet-lab and computational skills which are transferable to other settings.

References

Hildyard JCW, Riddell DO, Harron RCM, Rawson F, Foster EMA, Massey C, Taylor-Brown F, Wells DJ, Piercy RJ. The skeletal muscle phenotype of the DE50-MD dog model of Duchenne muscular dystrophy. Wellcome Open Res. 2022 Sep 23;7:238. doi: 10.12688/wellcomeopenres.18251.1. PMID: 36865375; PMCID: PMC9971692.

Amoasii L, Hildyard JCW, Li H, Sanchez-Ortiz E, Mireault A, Caballero D, Harron R, Stathopoulou TR, Massey C, Shelton JM, Bassel-Duby R, Piercy RJ, Olson EN. Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science. 2018 Oct 5;362(6410):86-91. doi: 10.1126/science.aau1549. Epub 2018 Aug 30. PMID: 30166439; PMCID: PMC6205228.

Bell SM, Evans JM, Greif EA, Tsai KL, Friedenberg SG, Clark LA. GWAS using low-pass whole genome sequence reveals a novel locus in canine congenital idiopathic megaesophagus. Mamm Genome. 2023 Sep;34(3):464-472. doi: 10.1007/s00335-023-09991-2. Epub 2023 Apr 11. PMID: 37041421; PMCID: PMC10600401.

Requirements

Essential:

• Must meet our standard MRes entry requirements.
• Interest in genomic and clinical research

Desirable:

• Prior bioinformatic experience in the field of genetics or genomics
• Clinical experience and interest in canine medicine or neurology  

This is a full-time (12months FTE) project commencing in October 2024, based at RVC's Camden and Hawkshead campuses.

Funding

This is a fully funded project that will cover tuition fees, stipend (at the home student rate) and research costs.

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

For more information on the application process and English Language requirements see How to Apply.

Deadline: Sunday 14th July 2024

We welcome informal enquiries - these should be directed to Richard Piercy: rpiercy@rvc.ac.uk.

Interview date and location: TBC