Studying the importance of metabolic stress in FSHD

Facioscapulohumeral muscular dystrophy (FSHD) is a muscle-wasting condition caused by a genetic mutation, which switches on a gene that shouldn’t normally be switched on. It is one of the most common forms of muscular dystrophy, and there is currently no effective treatment.

FSHD is caused by a change in the DNA that leads to the production of a protein called DUX4, which is not normally present in muscle. DUX4 is a transcription factor and so controls the activity of other genes, and the proteins made from these genes. DUX4 disrupts the careful balance of proteins within a muscle cell, ultimately leading to muscle weakness and wasting.

This project proposes to build on previous research by Prof Zammit’s team, in which they identified novel genes and mechanisms related to metabolic stress, which they believe are important in the pathology of FSHD. This project would aim:

(1) to identify the gene expression and metabolic changes that occur in muscle cells taken from people with FSHD

(2) to study how these changes affect the ability of these muscle cells to respond and adapt to varying oxygen availability, and

(3) to determine whether DUX4 modulates metabolism and oxidative stress (an imbalance in oxygen-containing molecules which causes harm to cells).