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.
The Molecular Mechanisms Of Anabolic Androgen Actions In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in musc ....We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in muscle. We will study the growth of mouse muscle cells in culture, and measure their rate of growth when treated with androgens. All cells contain certain factors that control their growth and replication, and we will test whether androgens activate these factors to increase growth. We will also study the effect of androgens on muscle in mice, to investigate complex effects that only occur in real muscle. We will neuter male mice, which causes muscle wasting. Neutered mice will then be treated with androgens or placebo, and we will compare the muscle growth effect of androgen treatment versus placebo. We will measure muscle strength, size, and the number of muscle cells in treated and placebo mice. We will also see if the effects of androgen require a particular protein, the androgen receptor, which acts as a lock-key mechanism in cells, to allow them to respond to androgens. We will make a strain of mouse with a non-functional version of the androgen receptor only in muscle cells. This will determine if the muscle growth effects of androgens occur through a direct action on muscle, or indirectly through acting on other tissues in the body. This information will ultimately allow us to design more targeted androgen therapies for muscle wasting, that act only on muscle.Read moreRead less
Novel Muscle Therapeutics Through Selective Beta-Adrenoceptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$603,608.00
Summary
Muscle wasting is an urgent and unmet health risk commonly associated with ageing; cancer, muscle diseases, and conditions including cardiovascular and metabolic disorders. Manipulating beta-adrenergic signalling is a therapeutic target for muscle wasting but treatments have so far been limited due to cardiaovascular side effects. Using cutting edge technologies, we will identify treatments that effectively separate beneficial effects on skeletal muscles from unwanted effects on the heart.
Using Gene Delivery Technologies To Define Novel Mechanisms Of Skeletal Muscle Adaptation, And Develop Muscle-directed Interventions For Frailty And Serious Illness
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
The focus of my research is to investigate the cellular mechanisms underlying regulation of skeletal muscle size and function in health and disease. By defining these processes we can establish the events contributing to muscle wasting and frailty commonly associated with serious illness and advancing age, and develop interventions to prevent/overcome this important contributor to poor health prospects and reduced survival.
Clarifying Molecular Role Of IGF-1:Ea Isoforms In Skeletal Muscle Hypertrophy And Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$394,718.00
Summary
The growth factor IGF-1 is proposed as a therapeutic agent to increase muscle mass and to reduce muscle wasting resulting from denervation, disuse, ageing and dystrophy. Understanding the precise mechanisms of IGF-1 action is essential for the potential therapeutic use of this factor. This research is focused on the molecular role of IGF-1 in healthy muscle and in the conditions of muscle wasting and degeneration.
Phosphoinositide 3-kinase Signalling And Skeletal Muscle Mass.
Funder
National Health and Medical Research Council
Funding Amount
$597,598.00
Summary
Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerat ....Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerationRead moreRead less
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.
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
Identification Of The Molecular Mechanisms By Which Mutations In FHL1 Lead To Protein Misfolding And Skeletal Muscle Disease
Funder
National Health and Medical Research Council
Funding Amount
$609,424.00
Summary
Skeletal muscle diseases result in debilitating muscle loss and may result from an error (mutation) within a gene. Mutations in FHL1 were identified as the cause of four different muscle diseases. Using purified FHL1, skeletal muscle cells and animal models we will investigate how FHL1 mutations cause muscle wasting, and loss of muscle strength.