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.
We will apply genome-wide approaches to identify the gene networks that regulate the self-renewal and the differentiation of muscle stem cells and their fusion to muscle fibres. These studies will deliver the first characterisation of the molecules and pathways implicated in these processes, which are essential steps of muscle growth.
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.
Determining The Pathobiology Of Human Sarcomeric Myopathies Using Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$509,541.00
Summary
Laing muscular dystrophy and ACTA1 congenital muscular dystrophy are severe muscle diseases with high morbidity. We will create zebrafish strains that carry these diseases and use these to understand the causes of muscle failure and investigate possible areas of treatment for these conditions.
Modelling Laminin Mediated Adhesion And Congenital Muscular Dystrophy In Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Congenital Muscular Dystrophy (CMD) is a muscle wasting conditions arising from mutations in the Lamina alpha 2 gene (lama2) gene. We have established zebrafish as a model system in which to determine the mechanistic basis of CMD pathology. We have isolated mutations in the zebrafish Lama2 gene and have determined that Lama2-deficient zebrafish accurately model the human condition. We aim to use the advantages of the zebrafish system to model treatments for muscular dystrophy
Molecular And Cellular Basis For Muscle Regeneration In Zebrafish.
Funder
National Health and Medical Research Council
Funding Amount
$541,104.00
Summary
Muscle repair occurs via the use of muscle stem cells, which provide skeletal muscle with its regenerative capacity. Muscle stem cells are particularly important in muscle diseases such as muscular dystrophies where muscle regeneration is an important factor in disease progression. We will identify the processes controlling muscle regeneration utilising zebrafish as a model organism. We hope this research will lead to an understanding of how muscle stem cells are generated.
The Role Of Scube Genes In Hedgehog Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
Cancer often results form the miss-regulation and-or mutation of genes that control tissue formation in the developing embryo. Particular sets of genes combine to form a signal transduction pathway that coordinates the cell's response to its environment during the course of normal fetal growth. One such pathway is called the Hedgehog signal transduction pathway which has been shown to coordinated cell division and patterning within malignant and normal tissues. Genes encoding components of this ....Cancer often results form the miss-regulation and-or mutation of genes that control tissue formation in the developing embryo. Particular sets of genes combine to form a signal transduction pathway that coordinates the cell's response to its environment during the course of normal fetal growth. One such pathway is called the Hedgehog signal transduction pathway which has been shown to coordinated cell division and patterning within malignant and normal tissues. Genes encoding components of this pathway are mutated in the most common forms of human cancers. Understanding how this pathway is regulated is critical to designing strategies to treat the onset and progression of these cancers. The studies outlined in this grant plan to study a new component of this pathway that we have identified in our laboratory, in an easy to study vertebrate model, the zebrafish embryo. We plan to study how this class of proteins, termed scube proteins, acts to control activation of the pathway. We hope this will lead to a fuller understanding of this process, and at the same time help understand the nature of the end result of the patterning process within the muscle cells that we are studyingRead moreRead less
Evaluation And Design Of Therapeutic Strategies Utilizing Zebrafish Genetic Models Of Duchenne Muscular Dystrophy.
Funder
National Health and Medical Research Council
Funding Amount
$632,438.00
Summary
Duchenne and Becker Muscular Dystrophy (MD) are allelic muscle wasting conditions arising from mutations in the dystrophin (DMD) gene. We have established zebrafish as a model system in which to determine the mechanistic basis of DMD pathology. We have isolated mutations in the zebrafish dystrophin gene and have determined that Dystrophin-deficient zebrafish accurately model the human condition. We aim to use the advantages of the zebrafish system to model treatments for muscular dystrophy.