Regulation Of Heart Development And Regeneration By DNA Methylation.
Funder
National Health and Medical Research Council
Funding Amount
$552,709.00
Summary
The adult mammalian heart has an extremely limited capacity for regeneration following a heart attack, which is in stark contrast to the robust regenerative capacity of the newborn heart. How and why mammals lose their ability to regenerate heart tissue after birth is not well understood. We propose a new approach to unravel the complex mechanisms that control gene expression during heart development in rodents and humans, which could provide new therapeutic avenues for heart regeneration.
Genome-wide Analysis Of Gene Regulatory Networks In Heart Development And Congenital Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,263,954.00
Summary
Despite advances in surgical methods and hospital critical care, congenital heart disease (CHD) remains the leading cause of non-infectious death in children in the first year of life. Severe CHD requires multiple surgeries and a lifetime of emotional and financial burden. In this proposal we will use new molecular and genetic approaches to ask how the network of genes that normally participates in heart development is controlled by regulatory factors, and how the network is disturbed in CHD.
Probing The Cardiac Gene Regulatory Network In Development And Congenital Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$518,118.00
Summary
In Australia, congenital heart disease (CHD) is the biggest killer of children under 5 years. Defects range from small holes to severe malformations requiring multiple surgeries and an uncertain future. Our appreciation of CHD mechanism is limited. Using cutting-edge technologies in genomics, biophysics and structural biology, we will study the mechanisms that lead to CHD at unprecedented resolution. Our project will progress the concept of personalized diagnosis and treatment of CHD.
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 individualĂs 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.
Defining The Role Of Nedd4 In Neural Crest Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$541,565.00
Summary
Neural crest cells are specialised stem cells that give rise to many tissues and organs during embryonic development. We recently identified an essential role for a regulatory protein in neural crest cells. Our research is aimed at understanding how this protein influences the growth of structures such as the heart and facial skeleton. Understanding these processes underpins the ultimate goal of implementing diagnostic and preventative medicine for highly prevalent congenital birth defects.
Identifying Genes Required For Vertebral Column And Heart Formation
Funder
National Health and Medical Research Council
Funding Amount
$950,418.00
Summary
Birth defects occur in about 3% of live births. These originate as the embryo forms, and we have previously shown that some of these are caused by gene mutation and/or environmental factors during gestation. However, the origins of many such defects remain unexplained. We will examine the DNA of patients to find gene mutations causing such defects. We will also test if mutations in these genes increase the likelihood of the embryo developing a defect if it is exposed to environmental stressors.
Using Nkx2-5 Knock-in Mouse Models To Understand Complex Cardiac Diseases
Funder
National Health and Medical Research Council
Funding Amount
$611,340.00
Summary
The most common cause of postnatal mortality is heart defects associated with mutation in transcriptional factors, of which NKX2-5 is the master gene. NKX2-5 is also involved in cardiac dysfunction in adults. We developed a unique mouse genetic approach that mimics human disease to study the mechanism behind this gene function. Our work paves the way to more efficient forecast, counseling and treatment strategies, reducing the socio-economic burden of congenital heart disease our community.
Novel Roles For Neural Crest Cells In Cardiac Morphogenesis
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Abnormal formation of the cardiac outflow tract leads to common malformations affecting over 1% of all births. Taking advantage of novel mouse models this grant aims to identify the molecular mechanisms by which neural crest cells control formation of the cardiac outflow tract. New information generated from this study stands to identify new targets which may be used for predictive testing and regenerative therapies.
Identification And Characterization Of The Molecular Mechanisms Of Cardiac Muscle Regeneration Regulated By The Epicardium In Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$540,772.00
Summary
Heart attack is a life-threatening disease that damages cardiac muscle. The human heart cannot create new muscle after the damage, which partly contributes to the high morbidity and mortality of this disease. Unlike humans, zebrafish, a small tropical freshwater fish, can naturally create cardiac muscle after injury. In this project, we will understand at the molecular level how zebrafish regenerate cardiac muscle, and provide insights for repairing damaged muscle in the human heart.