Excitation-contraction Coupling In Skeletal Muscle In Health, Exercise And Disease
Funder
National Health and Medical Research Council
Funding Amount
$623,621.00
Summary
Skeletal muscle dysfunction occurs in certain diseases, aging and exercise, and can deleteriously affect lifestyle and mobility. This project investigates the molecular mechanisms involved in the complex sequence of events that occur in each individual muscle fibre, starting from stimulation by a nerve through to the fibre contracting. This should give information about causes of skeletal muscle dysfunction in myotonia, heart failure and other situations, and help development of therapies.
To Improve The Diagnosis Of Limb-girdle Muscular Dystrophy Using New Genetic Techniques Of DNA Sequencing Known As Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$101,991.00
Summary
Diagnosis of Limb-girdle muscular dystrophy (LMGD) is complex with only about 50% success rate. New technology, Next Generation Sequencing (NGS) can identify a diagnosis substantially quicker and cheaper than standard methods, however is only available in research. The results of this study will form a core resource that can be augmented in the future to identify rarer forms of LGMD, so that all patients can be provided with a genetic diagnosis.
A Novel Cytoskeletal Structure In Muscle Is Associated With Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$371,250.00
Summary
A NEW PROTEIN NETWORK IN MUSCLE IS ASSOCIATED WITH MUSCLE DISEASE An intricate protein network connects the contracting mechanism of a muscle to the surrounding cell membrane. Disruption of this connection is one of the known causes of muscular dystrophy. For many patients however the cause of the disease is unknown. We have identified a new region within this protein network that is also associated with muscle disease in mice. A number of proteins that are involved in transmitting chemical mess ....A NEW PROTEIN NETWORK IN MUSCLE IS ASSOCIATED WITH MUSCLE DISEASE An intricate protein network connects the contracting mechanism of a muscle to the surrounding cell membrane. Disruption of this connection is one of the known causes of muscular dystrophy. For many patients however the cause of the disease is unknown. We have identified a new region within this protein network that is also associated with muscle disease in mice. A number of proteins that are involved in transmitting chemical messages from one part of the muscle cell to another are found at this same location. It is possible that disruption of these messages may lead to muscle disease. This project aims to establish the nature of the relationship between the proteins found in this newly identified region of the protein network and muscle diseases such as muscular dystrophy, in both animal models and in humans. We expect that this project may identify new markers for identifying the cause of muscle diseases in some patients and lead to better hopes for an eventual cure.Read moreRead less
Targeting Calcineurin For Improving Muscle Regeneration In Skeletal Muscle Disease
Funder
National Health and Medical Research Council
Funding Amount
$303,000.00
Summary
Muscular dystrophy is a term that covers a diverse group of inherited disorders characterised by progressive muscle weakness and wasting. Duchenne muscular dystrophy (DMD) is the most severe form, caused by a lack of a protein called dystrophin, which renders muscles fragile, susceptible to damage, and with a compromised ability to regenerate or repair after injury. The disease progresses to all muscles and DMD patients are dependent on a wheelchair before their early teens and die in their twen ....Muscular dystrophy is a term that covers a diverse group of inherited disorders characterised by progressive muscle weakness and wasting. Duchenne muscular dystrophy (DMD) is the most severe form, caused by a lack of a protein called dystrophin, which renders muscles fragile, susceptible to damage, and with a compromised ability to regenerate or repair after injury. The disease progresses to all muscles and DMD patients are dependent on a wheelchair before their early teens and die in their twenties. There is a profound need for treatments that can ameliorate the dystrophic condition and improve patient quality of life. Restoring or increasing a muscle's capacity to regenerate would help improve muscle function. We have convincing evidence that the calcineurin signal transduction pathway is important for successful muscle regeneration in mice with muscular dystrophy. There is growing excitement worldwide that stimulating calcineurin could attenuate the dystrophic pathology, however, little is known about the role of calcineurin signalling in human muscle disease. Our goals are to investigate the role of calcineurin signalling in muscular dystrophy and to examine its therapeutic potential for enhancing muscle regeneration. Our aim is to better understand the mechanisms controlling calcineurin signalling in muscles of dystrophic mice and in muscles of patients with DMD. A comprehensive series of physiological, molecular, biochemical, and immunohistochemical experiments will be performed to rigorously test our research aim. Understanding the role of the calcineurin pathway in muscle regeneration is important for the development of novel therapeutic strategies to delay the onset or slow the progression of muscle wasting and weakness. The findings will have broad clinical application for our understanding of muscular dystrophy with relevance to other conditions including ageing, AIDS, burns, cancer cachexia, and disuse atrophy, where muscle wasting occurs.Read moreRead less
Identifying Disease Genes For Neurogenetic Disorders Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$2,523,023.00
Summary
This project aims to identify novel disease genes, in other words, find genes, which have not previously been shown to cause human diseases when they are mutated. The collaborating laboratories on the project in Perth, Sydney, Melbourne and Boston, USA have a successful history in working together in finding human disease genes, harnessing, in the last few years, the now readily available power of next generation DNA sequencing to accelerate disease gene discovery.
An integrated platform built on efficient informatics concepts already implemented in international research infrastructures for large-scale data management, providing access to federated databases/registries, biobank catalogues, harmonised - omics profiles, and bioinformatics tools. Patient data types will be linked via a unique identifier “RD-ID” developed jointly with the US NIH. RD-Connect is a primary enabler for IRDiRC funded research to improve treatment and management of rare diseases
Targeting Beta-adrenergic Signalling To Improve Muscle Regeneration In Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$473,224.00
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. Modulating pathways regulating beta-adrenergic signalling has potential to attenuate the dystrophic pathology and to delay the onset or slow the progression of the muscle wasting and weakness in muscular dystrophy.
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
I am a biochemical geneticist working on inherited disorders that affect the musculoskeletal system. My major focus is determining the molecular basis of muscular dystrophies and bone and cartilage disorders.