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ContactMuscle stem cells, Dr J. morgan
Group/Researcher: Dr J. Morgan, Imperial College
This project aims to use models of a particular group of muscular dystrophies - called the dystroglycanopathies - to investigate satellite cell behaviour. Understanding more about this may help in the development of therapies using satellite cells.
Satellite cells, the stem cells of skeletal muscle, are responsible for the repair and replacement of muscle fibres that are lost as a result of injury or dystrophy. Satellite cells are located on muscle fibres, in a niche between the cell membrane and the connective tissue surrounding the fibre. They are normally in a dormant state, but are awakened into activity by muscle damage. Chemical signals released by the muscle fibre and the connective tissue activate satellite cells and “instruct” them to multiply and migrate to where they are needed.
There is communication between proteins that surround the outside of the muscle fibre - the extracellular matrix - and proteins that are located in the cell membrane of the muscle fibre itself. This communication is important for maintaining normal function and for regeneration by the satellite cells. In muscular dystrophies, some of these proteins may be missing or defective, leading to loss of communication between the muscle fibre and its surroundings. This results in breakdown of the muscle fibre. Some regeneration and repair mediated by satellite cells can occur, but it is often insufficient to replace the lost muscle fibres.
This project aims to use mouse models of a particular group of muscular dystrophies - called the dystroglycanopathies - to investigate satellite cell behaviour. The group wishes to identify whether there are defects in the satellite cells themselves or whether the satellite cells are normal, but do not behave properly due to defects in their environment, for instance lack of communication between the muscle fibre and the connective tissue. If the latter is the case, Dr Morgan aims to identify what the defects are and try to find ways of counteracting these in order to determine if manipulation of satellite cell behaviour could be used as a therapy in some forms of muscular dystrophy.
Value of Grant: Year 1 - £51,907
This project aims to use models of a particular group of muscular dystrophies - called the dystroglycanopathies - to investigate satellite cell behaviour. Understanding more about this may help in the development of therapies using satellite cells.
Satellite cells, the stem cells of skeletal muscle, are responsible for the repair and replacement of muscle fibres that are lost as a result of injury or dystrophy. Satellite cells are located on muscle fibres, in a niche between the cell membrane and the connective tissue surrounding the fibre. They are normally in a dormant state, but are awakened into activity by muscle damage. Chemical signals released by the muscle fibre and the connective tissue activate satellite cells and “instruct” them to multiply and migrate to where they are needed.
There is communication between proteins that surround the outside of the muscle fibre - the extracellular matrix - and proteins that are located in the cell membrane of the muscle fibre itself. This communication is important for maintaining normal function and for regeneration by the satellite cells. In muscular dystrophies, some of these proteins may be missing or defective, leading to loss of communication between the muscle fibre and its surroundings. This results in breakdown of the muscle fibre. Some regeneration and repair mediated by satellite cells can occur, but it is often insufficient to replace the lost muscle fibres.
This project aims to use mouse models of a particular group of muscular dystrophies - called the dystroglycanopathies - to investigate satellite cell behaviour. The group wishes to identify whether there are defects in the satellite cells themselves or whether the satellite cells are normal, but do not behave properly due to defects in their environment, for instance lack of communication between the muscle fibre and the connective tissue. If the latter is the case, Dr Morgan aims to identify what the defects are and try to find ways of counteracting these in order to determine if manipulation of satellite cell behaviour could be used as a therapy in some forms of muscular dystrophy.
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