Investigating the role of muscle stem cells in facioscapulohumeral muscular dystrophy
Project Leader: Dr Peter Zammit
Location: King's College London
Condition: Facioscapulohumeral muscular dystrophy (FSH)
Duration: 4 Years
Total Project Cost: £60,000 - Jointly funded with King's College London
Official Title: Does perturbed satellite cell function contribute to facioscapulohumeral muscular dystrophy?
Dr Zammit aims to use this 4 year PhD studentship to explore the role that muscle stem cells - also known as satellite cells - have in the progression of facioscapulohumeral muscular dystrophy (FSH). Dr Zammit will deliver two of the genes thought to be involved in FSH into muscle stem cells. This will allow him to find out what effect, if any, these genes have on how well the muscle stem cells are able to repair muscle.
Contents
- What are the researchers aiming to do?
- How will the outcomes of the research benefit patients?
- Background information
- Further information and links
What are the researchers aiming to do?
The role of muscle stem cells is to maintain and repair skeletal muscle. Researchers have been investigating the possibility of manipulating muscle stem cells to use them as a treatment for various forms of muscular dystrophy. Many aspects of muscle stem cell behaviour, however, are still not well understood and some major challenges remain. Muscle maintenance and repair by muscle stem cells does not work properly in FSH and it is thought that this may directly contribute to the disease progression.
FSH is most often caused by the deletion of a segment of DNA in a region called D4Z4. D4Z4 consists of a number of repeated sections of DNA. In FSH, the number of repeats in the D4Z4 region is less than in unaffected individuals. The exact function of the repeated section is unknown and a number of ideas exist as to what they may do. One idea is that by deleting some of these repeats, an abnormal protein is made (called DUX4). Another idea is that the loss of repeats affects neighbouring genes (e.g. DUX4c) and this affects how the muscle cell functions. Dr Zammit aims to find out if DUX4 and DUX4c affect how well the muscle stem cells are able to repair and regenerate muscle. Abnormal functioning of these genes could interfere with normal muscle stem cell function by either activating other genes at the wrong levels, time or place, or interfering with the operation of other important genes.
Dr Zammit and his student will deliver DUX4 and DUX4c into muscle stem cells and manipulate their activity in order to determine if they alter the ability of these cells to function normally. They will also examine how they affect other genes and in particular those that are important for maintaining normal muscle stem cell behaviour.
How will the outcomes of the research benefit patients?
This research is important as it gives scientists more information on how the genetic fault that causes FSH affects muscle and the way the muscle is able to repair and regenerate. It will also give important information on the viability of using muscle stem cells as a treatment for FSH in the future.
Background information
FSH is most commonly caused by the deletion of a repeated section of DNA called D4Z4. The exact reason why deleting this region of DNA might cause FSH is, however, not well understood. It is thought that D4Z4 might control genes on either side of the repeats, or may itself form part of the instructions for a protein. Research is still being carried out to determine which of these ideas might be correct.
Further information and links
Read more about FSH.
Read about our other FSH research project.
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