I am a physiologist investigating the molecular basis of normal function in skeletal muscle and the dysfunctions occurring in various muscle diseases and in fatigue. In addition, I investigate analogous dysfunction of calcium release and excitability occu
Establishing STARS As A Therapeutic Target To Reduce Muscle Wasting And Improve Muscle Function
Funder
National Health and Medical Research Council
Funding Amount
$446,189.00
Summary
Muscle wasting occurs rapidly with disuse after injuries occurring at work, during sport, with chronic disease and in road accidents. It is also a consequence of ageing. Muscle wasting and reduced muscle function places considerable financial strain on our health care system. We aim to use gene therapy and pharmacological interventions to increase the levels of a protein called STARS. We hypothesize that STARS will reduce disuse-induced muscle wasting, increase recovery and improve function.
Genetic Basis For Skeletal Muscle Formation And Regeneration In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$876,005.00
Summary
How does muscle grow and repair after injury or disease? This basic question in the focus of the research in this fellowship. Specific cells are put aside during development to generate the growth and provide stem cells required for regeneration. Using the advantages of the zebrafish system I will record the action of different stem cell populations during growth and disease. I will define the genes required for stem cell action and utilize this knowledge to create new therapeutic pathways.
Therapeutic Potential Of Skeletal Muscle Plasticity And Slow Muscle Programming For Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$780,476.00
Summary
There is no cure for DMD, a devastating, life-limiting muscle disease causing progressive muscle wasting in boys and young men. A potential therapy may come from modulating muscle activity patterns to promote a protective slow muscle phenotype through low-frequency stimulation protocols and/or well-described pharmacological ‘exercise mimetics’. This proposal will evaluate their therapeutic merit in mouse models of DMD to answer the key questions to advance this approach to the clinic.
Physiological And Pathological Effects Of Oxidation On Contractile Function In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Reactive oxygen molecules generated within muscle fibres in normal exercise and in pathological conditions, greatly affect muscle function by altering the responsiveness of the contractile proteins. This study investigates how various oxidative stresses affect particular reactive sites on key proteins controlling muscle contraction. The findings should identify key molecular changes involved in normal activity and the role oxidation plays in chronic muscle weakness in particular conditions.
Investigation Of The Roles Of Calcium-dependent Proteases In Muscle Damage And Disease
Funder
National Health and Medical Research Council
Funding Amount
$360,160.00
Summary
Muscle strength is important to the health and well-being of everyone. Skeletal muscle weakening occurs as a result of certain disease states, aging and prolonged inactivity due to illness-injury-surgery. This can result in the loss of normal activity and mobility and an increased incidence of falls and accidents, which impact considerably on health care costs. There is a family of proteins called calpains that have been linked to a number of factors affecting muscle function, however it is not ....Muscle strength is important to the health and well-being of everyone. Skeletal muscle weakening occurs as a result of certain disease states, aging and prolonged inactivity due to illness-injury-surgery. This can result in the loss of normal activity and mobility and an increased incidence of falls and accidents, which impact considerably on health care costs. There is a family of proteins called calpains that have been linked to a number of factors affecting muscle function, however it is not known how they are involved. Calpains are proteases, ie. they destroy other proteins, and they are regulated by the concentration of calcium inside a cell. The calcium concentration increases dramatically inside a muscle cell when it contracts. Inside a muscle cell it is important that there is tight regulation of the calpains to avoid them being activated inappropriately during normal use and causing muscle damage. In certain disease states, such as types of muscular dystrophy, it is known that the calcium concentration within resting muscle fibres is increased compared with healthy muscle fibres. We propose that as a consequence of this, the calpains will be less regulated and will cause damage to the muscle, which contributes to the muscle weakness seen in these diseases. Whilst calpains have been implicated with symptoms associated with muscle dystrophies, the role they play is certainly unclear. The objectives of our research proposal are to understand what factors influence i) where the calpains are located and ii) when and how much they are activated, within muscle fibres. We will compare this in healthy muscle and muscle from mdx mice, an animal model of Duchenne muscular dystrophy.Read moreRead less
Muscle Contracture In Multiple Sclerosis Prevalence And Rehabilitation
Funder
National Health and Medical Research Council
Funding Amount
$175,583.00
Summary
A population-based study of prevalence of muscle contracture will provide helpful information to health providers about the magnitude of the problem of contracture. This information will focus research efforts, and help health care providers to allocate resources appropriately. Recent studies have found that current treatments for contracture often provide transient or no effects. This project will test a promising new direction in treatment of contracture in people with multiple sclerosis.