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The research interests of our group focus on two main areas related to skeletal muscle: |
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| (1) | A central theme of our Research is to fully define the factors influencing the breakdown and repair of skeletal muscles, as well as factors involved in maintenance of muscle mass and function. These studies are carried out using the advanced techniques of molecular and cell biology at the light and electron microscopy level, in conjunction with tissue culture and animal procedures. This research relates to muscles damaged by injury, transplantation or diseases. A recent focus is on myofibre atrophy and hypertrophy with reference to muscle wasting that results from disuse, ageing and in disease. This information has applications to the metabolic syndrome and exercise. One aim of our research is to develop strategies to enhance muscle maintenance and repair in vivo. | |
| (2) | This knowledge forms the basis for potential treatments for inherited muscle diseases such as Duchenne Muscular Dystrophy (DMD). Previous research has focused intensively on cell therapies (including stem cells) to replace the defective dystrophin gene in the mdx mouse model of DMD, with much effort dedicated to preventing the massive initial loss of injected cultured donor muscle cells. These studies use a male Y- chromosome marker to identify and quantitate donor male cells implanted into female mdx host mice. We have tested the ability of many strategies to overcome the problem of this initial donor cell death, and also to enhance myoblast migration in vivo. Recent research is investigating strategies to reduce necrosis of dystrophic myofibres with an emphasis on the benefits of (i) elevated IFG-1 isoforms within muscle cells, (ii) specific blockade of inflammatory cells and cytokines such as TNFa and (iii) dietary interventions. The molecular basis of the proven protective effects of (i) elevated transgenic IGF-1 within myofibres and (ii) blockade of TNFa is being investigated at many levels. | |
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| Topics of particular interest: | ||
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The
study of early events to reseal damaged muscle fibres. |
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The
influence of growth factors and extracellular matrix components on the
activation, proliferation and fusion of myoblasts. Particular emphasis
is placed on the role and interaction of these factors in the in vivo
situation. |
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Effects
of transgenic over-expression of various isoforms of IGF-1 within skeletal
or cardiac muscle in mice. |
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The role of inflammatory cells and cytokines (especially TNFa) in the breakdown and repair of skeletal muscle. | |
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The
events which control myoblast fusion. |
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Muscle
growth and hypertrophy: in mouse and other animal models, humans, and
the Meat & Livestock industry. |
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Factors
affecting sarcopenia (age-related muscle wasting). |
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Signalling
controlling the balance between myogenesis and adipogenesis. |
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Animal
models of muscle diseases. |
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Exercise induced muscle damage. | |
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The
development of novel techniques for in vivo imaging of muscle damage and
repair. |
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