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.
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
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.
Systemic Approaches Of Myoblast Fusion In Vertebrates
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Myoblast fusion is a poorly understood process of crucial importance during muscle growth and repair. Furthermore, engineered myoblasts can be introduced to fuse with mature muscles, forming a stable hybrid organ within the adults, thus offering novel therapeutic possibilities in the future. In this research, we will undertake the first systemic, genome-wide approach to identify and characterise the gene networks underlying muscle fusion in vertebrates.
Molecular Characterisation Of Transverse Tubule Development In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$951,321.00
Summary
Muscle fibres contain an elaborate system of membranes that allow the fibre to contract. This proposal aims to understand how this membrane system develops and how this process is disrupted in disease.
Targeting A Novel Long Non-coding RNA That Is Dysregulated In Skeletal And Cardiac Muscle Disease
Funder
National Health and Medical Research Council
Funding Amount
$621,557.00
Summary
Recently, evidence suggests that cellular pathways that promote disease in skeletal and cardiac muscle, may be significantly influenced by a new class of molecules known as lncRNAs. Indeed a handful of studies have shown that therapies which target lncRNAs, can reduce disease severity. Thus, the identification of new lncRNAs that influence muscle health may present new therapeutic options to treat muscle diseases, where very few treatments currently exist. Here, we describe one such lncRNA.
Investigating Hippo Signalling As A Novel Cause Of Muscle Disease, And As A Target For New Interventions To Combat Frailty
Funder
National Health and Medical Research Council
Funding Amount
$460,509.00
Summary
We will explore the role of the Hippo signaling pathway in muscle development, repair and remodelling. We propose that this little-known pathway which affects organ development, is key for maintaining healthy muscles, and is affected in muscle wasting. Using gene therapy tools to alter this pathway in models of disease, we intend to clarify the role of Hippo signaling in muscle, and establish whether the pathway can be manipulated to treat physical frailty caused by muscle wasting.
Influence Of In Utero Environment On Diaphragm Structure And Function
Funder
National Health and Medical Research Council
Funding Amount
$494,966.00
Summary
The diaphragm is the major muscle involved in breathing. Normal function of the diaphragm is essential to survival. Preterm babies may be exposed to infection and other agents that interfere with diaphragm development and make breathing efforts weaker after birth, potentially leading to respiratory failure. This study will study diaphragms of preterm lambs to determine how fetal exposure to infection and steroids affect fetal diaphragm development, and if adverse effects are prevented by fetal t ....The diaphragm is the major muscle involved in breathing. Normal function of the diaphragm is essential to survival. Preterm babies may be exposed to infection and other agents that interfere with diaphragm development and make breathing efforts weaker after birth, potentially leading to respiratory failure. This study will study diaphragms of preterm lambs to determine how fetal exposure to infection and steroids affect fetal diaphragm development, and if adverse effects are prevented by fetal treatment with blocking agents.Read moreRead less
Defining The Molecular Regulation Of Muscle Stem Cell Action During Organ Growth
Funder
National Health and Medical Research Council
Funding Amount
$738,259.00
Summary
How do organs grow to develop a complex cellular structure. Organ growth needs a careful balance between cell commitment and stem cell self renewal to maintain tissue growth trajectories. How this balance is achieved at the cellular and molecular level remains unresolved for most organ systems. This application studies a specific stem cell pool within the zebrafish myotome and how it is used to drive organ growth.
Molecular Mechanisms That Generate And Activate Muscle Stem Cells During Growth And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$596,086.00
Summary
This study aims answer long standing questions in the field of muscle stem cells. Understanding how stem cell-driven muscle repair occurs has profound implications for our understanding of the pathology and treatment of muscle disease. Muscular dystrophies and myopathies are amongst the largest group of inherited disorders to afflict the human condition. It is our hope that the results of this research will lead to a better understanding of how treatments, stem cell based or otherwise, could be ....This study aims answer long standing questions in the field of muscle stem cells. Understanding how stem cell-driven muscle repair occurs has profound implications for our understanding of the pathology and treatment of muscle disease. Muscular dystrophies and myopathies are amongst the largest group of inherited disorders to afflict the human condition. It is our hope that the results of this research will lead to a better understanding of how treatments, stem cell based or otherwise, could be employed to correct such disorders.Read moreRead less