Investigators: Philipp Heher PhD, Professor Peter Zammit
Category: Research - Basic
Diseases can be treated more effectively if the causes/mechanisms underlying the symptoms are known. Facioscapulohumeral muscular dystrophy (FSHD) is incurable and is caused by a change in a particular region of DNA that leads to production of a protein called DUX4, that is not normally present in muscle. DUX4 is a 'transcription factor' meaning that it can control the expression of other genes by binding to their regulatory regions, and so can alter the type of proteins that are made by a cell. Thus, the carefully coordinated pattern of gene expression and protein production that enables skeletal muscle to function effectively is perturbed by the presence of DUX4. However, it is generally poorly understood how DUX4 causes the debilitating, progressive skeletal muscle weakness and wasting typical of FSHD.
We have examined gene expression changes in FSHD and DUX4-expressing muscle cells and found that pathways are suppressed that control generation of mitochondria and processes associated with mitochondrial function such as dealing with by-products of metabolism/respiration called reactive oxygen species (that cause oxidative stress). This is important as mitochondria generate energy for the cell to make muscle always work efficiently, from when resting to undergoing strenuous exercise.
In this project we will examine mitochondria structure, maintenance and function in FSHD muscle cells and investigate drugs that may improve mitochondria. This will give a better understanding of the cause of FSHD, with the long-term aim of finding new and more effective targeted therapies for FSHD to inform, support and underpin clinical trials.
Note: Start/End dates changed to match actual hire date of postdoc.