RVC Supervisor(s): Dr Androniki Psifidi, Professor Richard Piercy
Non RVC Supervisor: Emily Clark (The Roslin Institute, University of Edinburgh)
Department: Clinical Science and Services
Project Summary:
Exertional rhabdomyolysis (ER) is a common syndrome characterised by painful episodes of exercise-induced muscle stiffness and contracture, myofibre necrosis, myoglobinuria, and sometimes renal failure and even death. ER affects humans and many animal species, but horses appear particularly predisposed. The disease is common in Thoroughbred racehorses, but it also affects many UK pleasure horse breeds, especially Warmbloods. Despite significant welfare and financial implications, in most cases the underlying aetiopathogenesis remains unknown: ER has a genetic component but environmental factors also play an important role. In such complex diseases, causative genetic variants are often located in regulatory regions of the genome. Given that ER primarily affects muscles that are rich in fast twitch muscle fibre types, genes that are preferentially expressed within these fibres are good candidates for the study of ER. However, there is limited information on fibre type-specific genome regulation in horse muscle, which undermines investigative efforts. This project will address this shortfall by generating gene regulation, 3-Dimensional (3D) chromatin organisation architecture, and gene expression information for equine muscles with different primary functions and of different fibre types. By integrating results from a series of sophisticated functional genomic techniques with genome-wide association studies and whole genome sequencing data from Warmblood and Thoroughbred horses with ER, the goal is to provide mechanistic insights on equine ER. Key findings will be validated by comparing gene- and protein-expression in affected muscle from affected horses and controls.
This project represents the first study of equine skeletal muscle regulation at genome-wide level using ATAC-Sequencing and 3D-genomics. We will generate a foundation that will benefit equine genomic- and postgenomic-research in both basic and applied contexts with the potential to revolutionise prevention, management and therapy of ER and other myopathies.
The successful PhD candidate will acquire skills in a wide range of cutting-edge quantitative genetics, functional genomics, immunohistochemistry and wet lab skills. Further, given that this is an iCASE studentship, the doctoral student will benefit from working closely with an industrial partner and experience research and business strategy and training. The student will join a research team with numerous PhD students and post-docs, and will benefit from exposure to an extended global network of researchers interested in equine genetics, functional genomics, exercise physiology and muscle disorders.
Requirements
Essential
- Must meet our standard PhD entry requirements
- Excellent written English.
- Excellent organisational skills.
- Excellent oral and written communication skills.
- Excellent interpersonal skills, and able to work as part of team.
Desirable
Although not necessary, previous laboratory based or computational experience would be useful, such as MSc and/or undergraduate project work or work experience placements.
- Experience with R, SPSS, and Linux
- Programming experience
- Research experience working in a molecular biology or genetics lab.
- Understanding of the horse industry, veterinary medicine or exercise physiology
This is a competition funding studentship. If awarded the student will receive a 3 year fully-funded studentship, covering tution fees and stipend. This studentship is open to applicants eligible for "Home" fees. 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 to pay the “home” rate of tuition fees nor claim any financial support for their studies dependent on personal circumstances (including immigration status and residence history in the UK). To help determine whether you would be eligible for home fees please see the UKCISA's 'Who pays 'home' fees for higher education in England?' guide found here.
The studentship will commence October 2022.
How to Apply
For more information on the application process and English language requirements see please see How to Apply.
If you are interested in applying for this position, please follow the link below. Please use your personal statement to demonstrate any previous skills or experience you have in using both qualitative and quantitative research methods.
Interviews will take place over zoom between 14th and 25th March 2022.
We welcome informal enquiries - these should be directed to Dr Androniki Psifidi [Email Address Removed]
Deadline: 06/02/2022