Supervisor: Dr Yung-Yao Lin Co-supervisor: Professor Silvia Marino

Project Title: iPSC-derived myogenic progenitors as a novel experimental tool to study regeneration-enhancing therapeutic approaches in muscular dystrophy.

Applications are invited from enthusiastic graduates with a BSc (First or Upper Second) or MSc (Distinction or Merit). Previous research experience would be an advantage. This 3 year studentship will commence on 1st October 2015 and the applicant will be based in the School’s Whitechapel Campus. This is an exciting opportunity for a graduate from disciplines related to genetics, stem cell biology and regenerative medicine.

Background:
Skeletal muscle has the remarkable capacity to regenerate new muscle fibres after traumatic injuries or muscle degeneration due to genetic defects. The X-linked Duchenne muscular dystrophy (DMD) is the most common form of childhood muscular dystrophy caused by loss of dystrophin function, resulting in repeated cycles of muscle fibre degeneration and regeneration during which the capacity of muscle regeneration is progressively exhausted. The process of muscle regeneration requires the function of myogenic progenitors, such as satellite cells (a type of muscle stem cell) or pericytes (a type of vascular progenitor cells). The muscles of muscular dystrophy patients, however, are depleted of these myogenic progenitors. In addition, molecular mechanisms underlying activation of these cells are not well understood. Currently there is no cure for any form of muscular dystrophies. Recent advances in cellular reprogramming technologies and myogenic differentiation protocols offer the prospect of producing unlimited numbers of myogenic progenitor cells which can be derived from induced pluripotent stems cells (iPSC). Specifically, mesoangioblasts are stem/progenitor cells derived from a subset of pericytes and iPSC-derived mesoangioblasts have been shown to have the potential to ameliorate muscle degeneration. We previously found that overexpression of the PcG gene Bmi1, a chromatin modifier and transcriptional repressor, significantly enhances the regenerative capacity of the skeletal muscle in mouse models of DMD. It remains unclear, however, through what molecular and cellular mechanisms are myogenic progenitor cells regulated and whether these mechanisms are highly conserved in humans.

Aims:
The overall aim of this project is to generate and characterise a novel experimental tool to better understand the molecular and cellular mechanisms underlying skeletal muscle regeneration. The specific aims are to:
1. Establish a DMD patient-specific iPSC-based model for manipulating specific gene expression.
2. Delineate genetic pathways involved in regulating myogenic progenitor cell activity.

3. Assess skeletal muscle regeneration capacity by manipulating specific gene expression in DMD iPSC-derived myogenic progenitors.
The results from these analyses will not only elucidate molecular and cellular mechanisms underlying muscle stem cell regulation, but also lay important basis for developing pharmacological regulators of the signalling pathways critical for skeletal muscle regeneration.

This project will be jointly supervised by Dr Yung-Yao Lin and Prof Silvia Marino. Our laboratories are based at the Centre for Genomics and Child Health located in the Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London. Here the student will have access to a wide variety of cutting-edge technologies and core facilities, as well as interaction with researchers across a wide range of biomedical research. In the 2014 REF, QMUL was ranked 9th out of all UK multi-faculty institutions in overall research outputs, impact and environment. In Unit of Assessment 1 (Clinical Medicine), the aggregate score for Outputs, Impact and Environment placed Barts and the London Medical School 3rd nationally with a 90% of submitted material considered 3* or 4*. In terms of outputs, QMUL came 2nd nationally with 97.9% of outputs graded 3* or 4*.

Informal Enquiries can be made to: Dr Yung-Yao Lin e-mail: yy.lin@qmul.ac.uk

Funding Notes:

Studentships are open to applicants with either basic science or clinical qualifications and will be funded for 3 years. Studentships will include a stipend of £18500, PhD fees (at home/EU levels) and £5000 pa for consumables.

Non EU nationals are eligible to apply for this studentship but would need to pay the difference between UK/EU and International tuition fees themselves - Approximately £13500.00 per annum for a minimum period of three years.

Please apply online here.