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.
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.
Regulation Of Mammalian Heart Regeneration By The MiR-15 Family.
Funder
National Health and Medical Research Council
Funding Amount
$435,859.00
Summary
The inability of the adult heart to regenerate following a heart attack is a major contributor to the burden of heart disease in the developed world. We have recently discovered that, for a brief period after birth, the newborn heart can completely regenerate itself following injury. Understanding how and why the heart loses this remarkable capacity for regeneration shortly after birth may hold the key for developing cardiac regenerative therapies.
Therapeutic Potential Of Modulating Heat Shock Protein Expression For Muscle Wasting Disorder
Funder
National Health and Medical Research Council
Funding Amount
$1,172,146.00
Summary
Heat shock proteins help stressed proteins fold back to their original conformation and restore function. In a discovery published in Nature we identified induction of heat shock protein 72 (Hsp72) as a novel approach for muscular dystrophy and other conditions where there is inflammation and muscle weakness. This proposal will investigate whether Hsp72 induction is similarly effective in tackling the muscle wasting and weakness in conditions like ageing and frailty and in muscle injury.
Mechanisms Of Muscle Stem Cell Action In Injury And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$812,600.00
Summary
How do stem cells work in an organ or tissue to effect repair? Skeletal muscle is one of the few tissues that possesses the ability to regenerate after injury or disease but we understand very little about the processes that govern stem cell activation and the biology of self renewal, the mysterious process by which stem cell populations replicate themselves. Our zebrafish system will allow us to examine these questions directly in living muscle.
Systemic Approaches Of Myoblast Fusion In Vertebrates
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Myoblast fusion is a poorly understood process of crucial importance during muscle growth and repair. Furthermore, engineered myoblasts can be introduced to fuse with mature muscles, forming a stable hybrid organ within the adults, thus offering novel therapeutic possibilities in the future. In this research, we will undertake the first systemic, genome-wide approach to identify and characterise the gene networks underlying muscle fusion in vertebrates.
Reprogramming Macrophage Function In The Elderly To Rescue Impaired Inflammatory Responses To Muscle Injury
Funder
National Health and Medical Research Council
Funding Amount
$410,983.00
Summary
Muscle injury in the elderly often takes longer to heal than in younger people, however the cells responsible for this delayed healing are not well understood. Key inflammatory cells required for muscle repair in young hosts are macrophages. However, during aging we have shown that macrophage function is altered, but the mechanism is unknown. This project aims to determine the mechanisms behind age-related changes to macrophages and whether they can be targeted to improve elderly muscle repair.
The Role Of Innate Immune Responses In Cardiac Muscle Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$543,678.00
Summary
Heart attack is a life-threatening disease that damages heart muscle. Zebrafish can naturally restore lost heart muscle after injury, providing a model to understand mechanisms of heart regeneration. Here, we will explore previously uncharacterized events involved in heart regeneration, with particular focus on the immune response. We will study how immune responses are involved in heart muscle regeneration in zebrafish to find new insights for repairing damaged muscle in the human heart.
Seeing Is Believing: Imaging Muscle Maintenance And Repair
Funder
National Health and Medical Research Council
Funding Amount
$727,191.00
Summary
We will characterise the behaviour of muscle stem cells in vivo within their micro-environment in normal and regenerating adult muscles, using high-end imaging technologies and mouse lines that we recently created. This will allow correlating cellular behaviours with the activation of signaling pathways, chosen for their likely role in the activation of satellite cells. We will then modulate the activity of these pathways in the satellite cell niche to evaluate their function.
Identification And Characterization Of The Molecular Mechanisms Of Cardiac Muscle Regeneration Regulated By The Epicardium In Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$540,772.00
Summary
Heart attack is a life-threatening disease that damages cardiac muscle. The human heart cannot create new muscle after the damage, which partly contributes to the high morbidity and mortality of this disease. Unlike humans, zebrafish, a small tropical freshwater fish, can naturally create cardiac muscle after injury. In this project, we will understand at the molecular level how zebrafish regenerate cardiac muscle, and provide insights for repairing damaged muscle in the human heart.