Rescuing The Dystrophin-glycoprotein Complex To Protect Muscles From Wasting Conditions
Funder
National Health and Medical Research Council
Funding Amount
$833,340.00
Summary
Existing medical strategies to counteract severe muscle wasting disorders are compromised because of dysfunctional signalling around a cluster of proteins called the dystrophin-glycoprotein complex (DGC) located at the muscle membrane. To address this significant unmet medical need, this proposal investigates novel approaches to retain or restore DGC integrity at the muscle membrane with the goals of preserving and protecting muscles during serious wasting conditions.
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.
Cancer cachexia is a devastating disease characterised by muscle wasting, weakness and fatigue. It impairs patient quality of life and accounts for >20% of cancer-related deaths. This project will identify factors responsible for cancer cachexia and develop new strategies to alleviate wasting and weakness in cancer patients, to improve their quality of life and reduce mortality.
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.
Effects Of Replacement And Withdrawal Of Testosterone In Human Males On Muscle, Bone And Fat
Funder
National Health and Medical Research Council
Funding Amount
$156,682.00
Summary
Male sex hormone or androgen deficiency (AD) is a common, but under-diagnosed condition. AD decreases well being and contributes to muscle weakness, bone fragility and weight gain. Cutting edge technology will be used to help explain how AD may relate to these negative effects, particularly on muscle function. Given the importance of aging, frailty, osteoporosis and obesity, understanding the role of hormones in these conditions may have major implications for prevention and treatment.
The Influence Of A-actinin-3 On Muscle Structure, Metabolism, Performance And Response To Diet And Disease
Funder
National Health and Medical Research Council
Funding Amount
$624,355.00
Summary
We have identified a common genetic variant that results in absence of the fast muscle fibre protein a-actinin-3 in more than one billion humans worldwide. Loss of a-actinin-3 influences elite athletic performance, muscle bulk and strength in the general population, response to diet and exercise, and susceptibility to developing type 2 diabetes. We will now study mice and humans to determine how this gene influences variations in human performance, metabolism and severity of muscle disease.
Determining The Pathomechanics Of Muscle Weakness In Older Individuals With Toe Deformities In Order To Develop Evidence-based Intervention Strategies To Restore Foot Function
Funder
National Health and Medical Research Council
Funding Amount
$316,251.00
Summary
Hallux valgus and lesser toe deformities are highly prevalent foot problems in older people that can cause foot disfigurement, physical discomfort, and increase the risk of falling. This study will investigate how toe muscle weakness is affected by these toe deformities as the basis upon which to develop interventions that can restore foot function in older individuals, in order to reduce falls risk, foot pain and, in turn, improve independence and quality of life throughout ageing.
Knee Osteoarthritis After Anterior Cruciate Ligament Reconstruction: The Relationship Between Function And Neuromechanics
Funder
National Health and Medical Research Council
Funding Amount
$76,252.00
Summary
Anterior cruciate ligament (ACL) reconstruction allows most people to return to their previous level of function, but does not prevent the onset of knee osteoarthritis (OA). The development of OA in young people after ACL reconstruction may be caused by the initial injury, altered movement patterns, or changes in muscle control. This study will investigate the relationship between these factors. The findings will help to improve understanding of the causes of OA following ACL reconstruction.
Understanding The Human Hand In Grasping And How This Changes After Stroke
Funder
National Health and Medical Research Council
Funding Amount
$227,855.00
Summary
The hand allows remarkable feats of dexterity. But, paralysis of the hand severely limits daily activities and is common after stroke. We will determine key mechanisms that control the hand at the level of the brain and spinal cord. We will assess some limits that develop in the muscle itself. Stroke patients will be tested so that we can better understand the brain�s control of the hand and use this to enhance recovery of hand performance in those with impaired function.
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.