Investigation Of Childhood Onset Distal Myopathy Myosin Variants
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
This project aims to continue the research of this laboratory into the distal myopathies, a group of largely enigmatic genetic disorders, which most severely affect selected distal limb muscles, in other words mostly hand and foot muscles. The project has two parts. The first part aims to determine what causes the childhood onset distal myopathy which we first identified in a West Australian family. We localised the disease gene in this family to chromosome 14 in the first linkage of a distal my ....This project aims to continue the research of this laboratory into the distal myopathies, a group of largely enigmatic genetic disorders, which most severely affect selected distal limb muscles, in other words mostly hand and foot muscles. The project has two parts. The first part aims to determine what causes the childhood onset distal myopathy which we first identified in a West Australian family. We localised the disease gene in this family to chromosome 14 in the first linkage of a distal myopathy and researching this family and similar families from Europe we may have identified the gene. This project aims to prove that the candidate disease gene is the disease gene. The second part of the project aims to investigate another unknown distal myopathy in another Australian family, to try to localise and identify this disease gene.Read moreRead less
Identification Of Genetic Defects In Muscle Contractile Proteins
Funder
National Health and Medical Research Council
Funding Amount
$167,167.00
Summary
Congenital myopathies are a group of mostly inherited disorders which cause muscle weakness from birth. Some congenital myopathies can lead to the early death of the affected child, while other types are compatible with reaching adulthood. Like any diseases of childhood, the congenital myopathies cause great trauma to the families with an affected child. Couples at risk of having another affected child often opt to wait for prenatal diagnosis to become available for their particular disease befo ....Congenital myopathies are a group of mostly inherited disorders which cause muscle weakness from birth. Some congenital myopathies can lead to the early death of the affected child, while other types are compatible with reaching adulthood. Like any diseases of childhood, the congenital myopathies cause great trauma to the families with an affected child. Couples at risk of having another affected child often opt to wait for prenatal diagnosis to become available for their particular disease before attempting to have further children. However, prenatal diagnosis is only possible once the gene causing a disorder and the mutation in an individual family are identified. Identifying the disease-causing mutation may help the common feelings of guilt in the parents if it can be shown that the affected child has a new mutation, and there is nothing the parents could have done to stop their child having the disease. In the past, this Laboratory, the Molecular Neurogenetics Laboratory at the Australian Neuromuscular Research Institute, amongst others, has identified disease genes for the congenital myopathies. Prenatal diagnosis is now possible for those families whose disease-causing mutation has been identified. However the genetic cause of most of the congenital myopathies remains unknown. This Laboratory has become a reference centre for genetic studies of the congenital myopathies, especially the major form called nemaline myopathy. DNA samples have been sent here from around the world for study. This project aims to study this DNA, to identify other disease genes causing the congenital myopathies in order to help the families at risk with these conditions who currently cannot have prenatal diagnosis. Finding the genes also increases understanding of the diseases. It clarifies which proteins are involved. It allows studies of the mutated proteins to be undertaken. It makes it possible to understand how the diseases arise allowing future treatment of the conditions.Read moreRead less
The Unfolded Protein Stress Response In Inherited Skeletal Disease: Mechanism And Therapeutic Strategies
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
In genetic diseases, gene mutations commonly cause proteins to fold abnormally. This can cause cell stress resulting in cell death. Our studies will determine the role of cell stress in a clinically important group of skeletal diseases caused by collagen mutations. We will also test how we can use small chemicals to alleviate the damage done to the cells by the misfolded proteins, in the hope that this approach will provide new therapeutic strategies for these disorders.
Defintion Of Dystrophin Functional Domains According To Exon Boundaries To Optimise Splice Switching Therapies For DMD
Funder
National Health and Medical Research Council
Funding Amount
$520,765.00
Summary
Duchenne muscular dystrophy is a relentlessly progressive muscle wasting disorder, with a predictable outcome and no effective treatment. Splice manipulation has the potential to reduce the severity of the disease, improve the quality of life for patients and reduce health care costs. The definition of dystrophin functional domains according to exon boundaries will allow the most effective treatment strategies for each mutation to be developed.
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.
Genetic Basis For Skeletal Muscle Formation And Regeneration In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$876,005.00
Summary
How does muscle grow and repair after injury or disease? This basic question in the focus of the research in this fellowship. Specific cells are put aside during development to generate the growth and provide stem cells required for regeneration. Using the advantages of the zebrafish system I will record the action of different stem cell populations during growth and disease. I will define the genes required for stem cell action and utilize this knowledge to create new therapeutic pathways.
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.
Novel Approach And Insights Into Muscle Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$642,401.00
Summary
The successful use of stem cell therapy absolutely requires the longterm intergration of the therapeutic cells into the target tissue. This application will adapt a chemotherapy-based strategy to drive the successful incorporation and growth of healthy muscle stem cells into diseased muscle. This study will both enhance our understanding of muscle stem cells and provide proof-of-principle for a universal approach to the uptake of stem cells by a target tissue.
The Role Of Notch Signalling In Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
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. Defective Notch signalling has been implicated in the poor regenerative response of aged muscles and similarly in dystrophy based on our preliminary data. Modulating Notch signalling could therefore delay the onset or slow the progression of DMD.