Understanding The Opposing Roles Of SWI-SNF In The Control Of Gene Programs For Pathological Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$476,258.00
Summary
Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression.
Targeting The NLRP3 Inflammasome And Interleukin-18 In Hypertensive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$1,241,115.00
Summary
Heart failure is a common complication of hypertension and a major cause of death and disability worldwide. This project will characterise a newly identified inflammatory pathway that we believe to be a major cause of the enlargement and scarring of the heart that accompanies hypertension. We will also trial drugs that block this inflammatory pathway to determine their suitability as future therapies for this devastating disease.
Targeting PI3K-regulated MicroRNAs To Treat Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$532,593.00
Summary
Current therapeutics largely delay heart failure progression rather than regressing it. New therapeutic strategies with the capability of improving function of the failing heart are thus greatly needed. The primary goal of this study is to determine whether novel regulatory genes can enhance cardiac function in a setting of heart failure. Ultimately, technologies that target these genes may lead to innovative pharmacotherapies in the clinical management of heart failure.
Transcriptional Regulatory Complexes Associated With Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$474,517.00
Summary
Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression. It has been well known that a group of genes are altered (up or down) in the heart under conditions such as heart muscle overgrowth (ie ....Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression. It has been well known that a group of genes are altered (up or down) in the heart under conditions such as heart muscle overgrowth (ie hypertrophy), aging or of abnormal beating function. The reasons for such altered gene activity remain poorly understood. Although recent studies from research on genetics or cancer have revealed the important role of the DNA and DNA-bound proteins (called histone) in the control of gene activity, this has rarely been studied in the heart. In this project, we will test our hypothesis that DNA-histone structure is a key factor that control gene activities in ageing and diseased heart. This proposal is supported by our recent findings showing that in the hypertrophied heart, such DNA-histone structure did alter in such a way that fits well with alterations in gene activity. We have planned a series of studies to test this hypothesis in a systematic fashion. A number of sophisticated and cutting-edge techniques and experimental models of heart hypertrophy will be used. We will analyse changes in activities of a number of selected genes in the heart and also analyse changes in DNA-histone structures and chemical modifications at particular regions. These changes will then be linked together. We will also explore the possibility of modulating DNA-histone structure, thereby controlling the degree of cardiac hypertrophy. This project is the joint efforts of scientists with substantial experience in research on gene activity and heart diseases, and is highly likely to generate novel information to and hold significant therapeutic potential.Read moreRead less
Targeting Lipids Regulated In A Setting Of Physiological Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$489,970.00
Summary
Existing heart failure therapies largely delay heart failure progression rather than reversing the disease. New therapeutic strategies with the ability of improving function of the failing heart are thus greatly needed. The primary goal of this study is to determine whether lipids that are secreted by the heart in a setting of “good” physiological heart growth (as occurs with exercise) can be targeted to restore function of the failing heart.
Linking Early Heart Growth Stress And Adult Cardiopathology: A New Role For Autophagy
Funder
National Health and Medical Research Council
Funding Amount
$524,013.00
Summary
An enlarged heart at maturity is a major risk factor. The goal of this project is to understand how cardiac growth abnormality in the neonate contributes to adult growth pathology. We have recently discovered that a type of stress-triggered cell death (autophagy) is increased in rodent neonatal hearts which later become enlarged, and that this cell death is regulated by the hormone angiotensin II. We will study the mechanisms involved to identify intervention opportunities to normalize growth.
New Gene Discovery In Familial Hypertrophic Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$418,493.00
Summary
Familial hypertrophic cardiomyopathy is a genetic heart disorder which affects 1 in 500 of the population, and can lead to heart failure and sudden death. Identification of the genetic causes of hypertrophic cardiomyopathy has important implications for our understanding of this disease, and in translating these genetic discoveries into better diagnostic and prevention strategies in at-risk families. This research proposal seeks to perform a comprehensive clinical and genetic investigation of pe ....Familial hypertrophic cardiomyopathy is a genetic heart disorder which affects 1 in 500 of the population, and can lead to heart failure and sudden death. Identification of the genetic causes of hypertrophic cardiomyopathy has important implications for our understanding of this disease, and in translating these genetic discoveries into better diagnostic and prevention strategies in at-risk families. This research proposal seeks to perform a comprehensive clinical and genetic investigation of people with familial hypertrophic cardiomyopathy.Read moreRead less
Roles Of Interleukins, Chemokines And Circulating Cells In Cardiac Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$434,134.00
Summary
Cardiac fibrosis is a disease of the heart in which large amounts of collagen are deposited within the heart tissue. This leads to poor heart function and may also lead to sudden death due to arrhythmias (abnormal electrical pulses). This study sets out to define the role of substances called interleukins and special circulating cells called lymphocytes, macrophages and progenitor cells in the development of cardiac fibrosis.