(B/O DR. Androniki Psifidi)
Title: Genomic and transcriptomic characterisation of Duchenne Muscular Dystrophy in a canine model
RVC Supervisor(s): Professor Richard Piercy, Professor Dominic Wells
RVC Principal Supervisior: Dr Androniki Psifidi
Department: Clinical Sciences and Services
Duchenne muscular dystrophy (DMD) is a lethal, X-linked disease that causes progressive muscle degeneration, cardiomyopathy and respiratory failure in 1 in 5,000 humans; the disease also occurs in dogs. There are various treatments in use or under development, but there is still no cure. The disease is caused by mutations in the DMD gene that result in a near complete absence of dystrophin (a protein required for normal muscle function) in skeletal and cardiac muscle.
Differences in the onset and progression of the disease in different muscles and among individuals suggest that genetic modifiers play a key role. Although major progress in defining the pathogenesis of DMD has been made, research on understanding the genetic factors contributing to disease severity is at an early stage.
Dog models of DMD are powerful for the investigation of pathogenesis and for identification and testing of new treatments, since the disease phenotype is similar to humans; further, canine gene orthologues are available for 92% of human genes and, compared to mice, dogs are more similar to humans in body and organ size and immune response profiles.
With access to muscle tissues and DNA from DMD-affected dogs, the student will perform genome-wide association studies and examine transcriptomic profiling in conjunction with pre-existing, extensive and comprehensive longitudinal phenotypic data. The student will learn cutting-edge genetic and bioinformatic technologies, and relevant wet lab techniques to explore DNA-array, whole-genome sequencing and RNA- sequencing data to identify genetic modifiers and gene networks underlying DMD and potentially, their correction via gene therapy or gene editing.
Our findings will facilitate the identification of phenotypic, genomic and molecular biomarkers for the prognosis of DMD as well as targets for drug discovery, resulting in an improvement of human and animal lifespan and welfare.
Application deadline: 2 July 2017