Identification of genetic modifiers enhancing muscle regeneration using patient-specific human iPSC models

Muscular dystrophies are debilitating genetic diseases characterised by progressive weakness and wasting of skeletal muscle, which is responsible for voluntary movements and breathing. Gene mutations lead to loss of muscle fibres and their replacement with fat and connective tissue. Current standards of care can only delay loss of ambulation, cardiac and respiratory problems. Some muscular dystrophies cause premature death.

Muscle stem cells are responsible for muscle regeneration. However, it is difficult to isolate human muscle stem cells and to maintain their regenerative potential during expansion in culture. In this project, we aim to identify genetic modifiers that enhance stem cell-mediated muscle regeneration in the context of muscular dystrophy and validate potential therapeutic targets for developing novel treatments. To this end, we will exploit our well-established expertise, including patient-specific induced pluripotent stem cells (iPSCs), transgene-free myogenic differentiation and high-content screening platform.

Duchenne muscular dystrophy (DMD) is the most common and currently incurable neuromuscular condition caused by mutations in the dystrophin (DMD) gene. Enhancing muscle regeneration without restoring dystrophin expression represents a promising therapeutic strategy universal to all DMD patients. We propose to perform a genome-wide genetic screen to identify genetic modifiers that are capable of enhancing muscle regeneration in the absence of dystrophin. To do this, we will use patient-specific DMD iPSC-derived myogenic progenitors in combination with a human siRNA library and high-content screening platform. This project will have a significant impact on developing novel therapies for muscular dystrophies.

Applications are invited from highly motivated candidates with at least an upper-second class honours degree in an area relevant to the project (eg Genetics, Molecular and Cellular Biology, Biomedical Sciences). Proficient English language skills are essential. Potential candidates should contact Dr Yung-Yao Lin (yy.lin@qmul.ac.uk) with their CV (including details of two referees) and a personal statement describing their suitability for this project.