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.
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.
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.
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.
Evaluation And Design Of Therapeutic Strategies Utilizing Zebrafish Genetic Models Of Duchenne Muscular Dystrophy.
Funder
National Health and Medical Research Council
Funding Amount
$632,438.00
Summary
Duchenne and Becker Muscular Dystrophy (MD) are allelic muscle wasting conditions arising from mutations in the dystrophin (DMD) gene. We have established zebrafish as a model system in which to determine the mechanistic basis of DMD pathology. We have isolated mutations in the zebrafish dystrophin gene and have determined that Dystrophin-deficient zebrafish accurately model the human condition. We aim to use the advantages of the zebrafish system to model treatments for muscular dystrophy.
Molecular Characterisation Of Transverse Tubule Development In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$951,321.00
Summary
Muscle fibres contain an elaborate system of membranes that allow the fibre to contract. This proposal aims to understand how this membrane system develops and how this process is disrupted in disease.
DHPR ? Subunit Binding To A Variably Spliced Region Of RyR1: A Role In EC Coupling And Myotonic Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
We have uncovered a communication pathway between two ion channel molecules in muscle cells that underlies human movement. The pathway is critical in normal mobility and is disrupted in myotonic dystrophy. We will study the molecular components of this pathway to understand normal body function and abnormal function in mytotonic dystrophy. The work will facilitate the design of drugs to relieve the mytotonic dystrophy myopathy and form new and much needed class of specific muscle relaxants.
Investigating Follistatin-based Interventions For Long Term-protection Against Frailty Associated With Chronic Illness And Aging
Funder
National Health and Medical Research Council
Funding Amount
$987,169.00
Summary
Effective therapies are urgently needed to combat frailty arising from muscle wasting associated with chronic illness and aging. The proposed studies will investigate the prospects of developing novel short-term interventions that can confer long-term benefits for preventing and treating muscle wasting associated with chronic illness and advanced aging.