Mapping Neurodevelopmental Disorders In A Zebrafish Model
Funder
National Health and Medical Research Council
Funding Amount
$2,760,520.00
Summary
The way in which the brain develops differently in neurodevelopmental disorders such as autism is hard to reveal in humans, but can be addressed in a zebrafish model. Using cutting-edge imaging and computational techniques, this project will investigate how neural representations of the world develop differently between normal zebrafish and zebrafish mutant for a gene that causes autism. This will provide new insights into the mechanisms of altered circuit development in autism.
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.
Tissue-dependent Proregenerative Mechanisms In Adult Vertebrates
Funder
National Health and Medical Research Council
Funding Amount
$638,742.00
Summary
This proposal addresses how immune cells participate in regeneration of damaged organs in adult zebrafish. Unlike mammals, zebrafish have a remarkable capacity to regenerate their various body parts in adulthood, providing a model to understand how regeneration capacity might be induced in humans. The proposed study will define mechanisms of immune-mediated regeneration that could provide new cellular and molecular targets for stimulating replacement of damaged organs in the human injury setting
Identification And Characterisation Of Genes Required For Cardiac Morphogenesis
Funder
National Health and Medical Research Council
Funding Amount
$434,706.00
Summary
The heart is the first organ to become functional as an embryo forms, reflecting its critical role in sustaining life. Mistakes that occur as the heart develops have devastating consequences for an individualÍs survival and health. We have identified two zebrafish mutants with heart defects and, using sophisticated imaging and genetic studies, will investigate these defects and identify the genes responsible. This research will improve our understanding of correct and diseased heart formation.
Examining An Extracellular Matrix Regulator Required For Cardiovascular Development
Funder
National Health and Medical Research Council
Funding Amount
$732,600.00
Summary
Cardiovascular disease (CVD) is the highest cause of death in Australia. Specific genes are required for correct assembly and function of the heart and vessels but disease will result if those genes are defective. To diagnose and treat CVD, we must first understand how these genes function. This project will investigate mouse models with genetic defects resulting in CVD. It will determine how and why the diseases occur and investigate a potential therapeutic option for intervention in CVD.
Characterisation Of A Newly Identified, Indispensible, Transcriptional Regulator Of Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$535,224.00
Summary
Lymphatic vessels form via lymphangiogenesis: growth of lymphatics from pre-existing vessels. This process is amenable to therapeutic intervention during metastasis because lymphatics support tumour spread. We discovered a gene that is essential for lymphangiogenesis to occur. We will investigate the control of lymphangiogenesis by this new factor. We aim to understand how it controls lymphatic vessel formation and identify genes within this pathway that have novel therapeutic potential.
A Critical New Signaling Axis In Lymphatic Vascular Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$700,784.00
Summary
The lymphatic vasculature is a crucial part of our vascular system required for tissue fluid drainage and maintenance of fluid homeostasis. Lymphatic vessels play major roles in vascular pathologies and in the spread of solid tumours during cancer progression. We have discovered a new molecular regulator controlling the formation of lymphatic vessels. This project will determine the signalling pathway employed by this new regulator and potential for future therapeutic applications.
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 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
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.