Development Of New Heart Failure Therapeutics By Analysing Signalling In Heart Failure As A Network
Funder
National Health and Medical Research Council
Funding Amount
$314,965.00
Summary
After detailed analysis of cell signalling in diseased heart tissue we will facilitate the discovery of new therapeutic drug targets to stop the progression of heart failure in its early stages. It is hoped that the detailed analysis of heart failure signalling as a network rather than as individual pathways will enable the discovery of drugs which are more successful in stopping the progression of heart failure than the currently available drugs.
Role Of Sensory Neurons In Obstruction-induced Bladder Overactivity
Funder
National Health and Medical Research Council
Funding Amount
$340,986.00
Summary
About 20% of people over the age of 40 have the clinical syndrome of an “overactive bladder”, which causes symptoms of urgency, frequency and incontinence. The mechanisms causing bladder overactivity are not known. This project will identify sensory neurons, which become overexcited, and determine which mediators and ionic channels are responsible for this. Our new data will identify selective pharmacological targets for new therapies and diagnostic tools for these distressing bladder disorders.
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.
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
Structural And Functional Consequences Of Left Ventricular Hypertrophy Regression.
Funder
National Health and Medical Research Council
Funding Amount
$293,036.00
Summary
Left ventricular hypertrophy (LVH) is a thickening of the heart muscle walls that occurs in a variety of cardiovascular diseases, including high blood pressure, coronary artery disease, cardiac valve disorders and heart dilatation. The presence of LVH increases the risk of developing heart attacks, heart failure and death. Treatment of these disorders is a major component of our escalating health-care costs. Consequently, reversal of LVH may have significant benefits to individual patients and s ....Left ventricular hypertrophy (LVH) is a thickening of the heart muscle walls that occurs in a variety of cardiovascular diseases, including high blood pressure, coronary artery disease, cardiac valve disorders and heart dilatation. The presence of LVH increases the risk of developing heart attacks, heart failure and death. Treatment of these disorders is a major component of our escalating health-care costs. Consequently, reversal of LVH may have significant benefits to individual patients and society in general. We propose to develop a mouse model of an inherited form of LVH that is caused by gene mutations in heart muscle proteins. This model will enable us to study in detail the disease processes that cause LVH and the effects of reversing LVH. This information will be invaluable for determining the best ways of treating patients with LVH.Read moreRead less
Inositol Polyphosphate 1-phosphatase, A Novel Anti-hypertrophic Factor
Funder
National Health and Medical Research Council
Funding Amount
$399,750.00
Summary
Growth of the heart muscle cells occurs after heart attack and in people with high blood pressure or who suffer from diseases such as diabetes. Such growth leads eventually to the development of heart failure, a major cause of death and disability in western societies. We have identified a novel inhibitor of this growth, an enzyme that destroys a signalling intermediate called inositol(1,4)bisphosphate (or IP2). We now need to define how reduction in IP2 reduces growth and whether it provides a ....Growth of the heart muscle cells occurs after heart attack and in people with high blood pressure or who suffer from diseases such as diabetes. Such growth leads eventually to the development of heart failure, a major cause of death and disability in western societies. We have identified a novel inhibitor of this growth, an enzyme that destroys a signalling intermediate called inositol(1,4)bisphosphate (or IP2). We now need to define how reduction in IP2 reduces growth and whether it provides a useful target for therapy.Read moreRead less
Value Of Central Blood Pressure For GUIDing ManagEment Of Hypertension (BP GUIDE Study)
Funder
National Health and Medical Research Council
Funding Amount
$339,553.00
Summary
A pressure pulse may be felt at the wrist with every heart beat. New technology allows the analysis of this pulse and measurement of blood pressure (BP) at the heart (central BP) . This information may help doctors improve the decision making process regarding a patient's risk related to BP as well as the effect of drug treatment. The study aims to test this theory. It is expected that the new technology will improve the way people with high BP are identified and treated.
Phosphoinositide 3-kinase Signalling And Skeletal Muscle Mass.
Funder
National Health and Medical Research Council
Funding Amount
$597,598.00
Summary
Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerat ....Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerationRead moreRead less
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.
Periodontal Mesenchymal Stem Cells For Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$358,000.00
Summary
Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characteriz ....Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characterize these cells and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.Read moreRead less