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.
Muscle Fusion Defects May Be A Common Cause Of Human Dystrophies
Funder
National Health and Medical Research Council
Funding Amount
$391,419.00
Summary
While muscle fusion is a crucial step of muscle formation, it is surprising that human muscle diseases were never associated with muscle fusion defects. We have recently undertaken a genome-wide functional screen using a mouse muscle cell line. We identified 21 genes that were previously associated with muscle dystrophies in human. The aim of this project is to examine the role of those genes during muscle fusion in vivo, using the chick embryo, mouse mutants and lines from patients as models.
The Role Of Notch Signalling In Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, caused by a lack of a protein called dystrophin. Dystrophic muscles are fragile, prone to injury, and have a compromised ability to regenerate after damage. Defective Notch signalling has been implicated in the poor regenerative response of aged muscles and similarly in dystrophy based on our preliminary data. Modulating Notch signalling could therefore delay the onset or slow the progression of DMD.
Targeting A Novel Long Non-coding RNA That Is Dysregulated In Skeletal And Cardiac Muscle Disease
Funder
National Health and Medical Research Council
Funding Amount
$621,557.00
Summary
Recently, evidence suggests that cellular pathways that promote disease in skeletal and cardiac muscle, may be significantly influenced by a new class of molecules known as lncRNAs. Indeed a handful of studies have shown that therapies which target lncRNAs, can reduce disease severity. Thus, the identification of new lncRNAs that influence muscle health may present new therapeutic options to treat muscle diseases, where very few treatments currently exist. Here, we describe one such lncRNA.
Molecular Basis Of Ca2+-dependent Disruption Of EC-coupling And Weakness In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$530,976.00
Summary
One major cause of weakness in skeletal muscle appears to stem from damage to the mechanism controlling release of calcium ions from internal stores and consequent contraction. This project examines whether the damage is due to excessive levels of intracellular calcium ions activating enzymes that cut a particular vital molecule controlling calcium release. The findings could identify a major factor in muscle weakness in muscular dystrophy and other conditions and lead to specific therapies.
Determining The Pathobiology Of Human Sarcomeric Myopathies Using Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$509,541.00
Summary
Laing muscular dystrophy and ACTA1 congenital muscular dystrophy are severe muscle diseases with high morbidity. We will create zebrafish strains that carry these diseases and use these to understand the causes of muscle failure and investigate possible areas of treatment for these conditions.
Modelling Laminin Mediated Adhesion And Congenital Muscular Dystrophy In Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Congenital Muscular Dystrophy (CMD) is a muscle wasting conditions arising from mutations in the Lamina alpha 2 gene (lama2) gene. We have established zebrafish as a model system in which to determine the mechanistic basis of CMD pathology. We have isolated mutations in the zebrafish Lama2 gene and have determined that Lama2-deficient zebrafish accurately model the human condition. We aim to use the advantages of the zebrafish system to model treatments for muscular dystrophy
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.
Targeting The TGF-beta Signalling Pathway To Improve Muscle Growth And Development In Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy. Dystrophic muscles are fragile, prone to injury, and do not regenerate well after injury. Modulating cell signalling pathways that are involved in muscle growth has the potential to attenuate the severity of the dystrophic pathology, to delay the onset or slow the progression of the muscle wasting and weakness, and to improve muscle growth and development in muscular diseases.