Regulation Of RyR2 Channels By Calmodulin In Healthy And Diseased Hearts
Funder
National Health and Medical Research Council
Funding Amount
$614,421.00
Summary
In the heart, RyR2 is responsible for intracellular Ca2+ release. The RyR2 is comprised of a Ca2+ channel and accessory proteins such as CaM that regulate channel activity. Evidence suggests that RyR2 regulation by CaM is altered in heart failure and human arrhythmia syndromes, but there has been no direct evidence for this. We will provide this direct evidence plus determine how CaM regulates RyR2 channels and intracellular Ca2+ release and how this leads to cardiac arrhythmias.
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.
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.
New Cardiac Ryanodine Receptor Inhibitors For The Treatment Of Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
We have discovered that a protein that is recognized for its role in phase II detoxification can also modify the calcium signaling that underlies heart function. The small part of the protein that is active in heart tissue differs from the enzyme center that supports detoxification and can thus be used as a therapeutic agent in heart failure and in genetic cardiac conditions. The project is to develop the cardio-active part of the protein for maximum efficacy and for eventual clinical use.
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.
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.
A Fully Implantable Self Powered Extra Aortic Counterpulsation Device? For Translational Development In Hypertensive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$901,586.00
Summary
The development of a low cost self-powered cardiac aortic assist device to improve blood flow to the heart and rest of the body. The device is placed on the external surface of the large blood vessel (aorta) leaving the heart and provides gentle counterpulsation to improve blood flow. This aortic cardiac assist device is a therapeutic treatment for early stage heart failure.
Regulation Of Endogenous Heart Regeneration By An Anti-fibrotic MicroRNA.
Funder
National Health and Medical Research Council
Funding Amount
$440,949.00
Summary
In contrast to the adult heart, the newborn heart undergoes scarless healing following a heart attack. The molecular mechanisms that govern heart regeneration in newborn mammals are not fully understood. The goal of the current study is to determine the role of a recently identified family of molecules known as microRNAs in the regulation of scarless healing. We propose a novel strategy for re-activation of microRNAs in the adult heart to promote regeneration following heart attack.
Development Of Endpoints For Catheter Ablation Of Non-mappable Scar-related Ventricular Tachycardia.
Funder
National Health and Medical Research Council
Funding Amount
$176,686.00
Summary
Ventricular tachycardia is a dangerous heart rhythm disturbance that affects people with scarring in the heart such as those with prior heart attacks or heart failure. Catheter ablation procedures, using wires passed from the groin, can be used to burn the short-circuits related to the scar. However in the majority of cases, it is very difficult to know when enough burning has been performed. This project aims to develop and validate several electrical and imaging endpoints for this procedure.
The Role Of The Cytoskeleton In Communication Between The L-type Ca2+ Channel And The Mitochondria In Cardiac Pathology
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
The L-type calcium channel is a protein in the membrane of heart muscle cells responsible for maintaining normal rhythm and contraction. We have shown that the channel can also regulate the function of the energy producing part of the cell (mitochondria). This occurs with the assistance of proteins that maintain cell architecture. We will test whether this association is altered in human disease where the cell architecture is disrupted to determine the mechanisms for poor energy supply.