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CCR4/NOT Complex Is A Conserved Regulator Of Heart Function
Funder
National Health and Medical Research Council
Funding Amount
$467,567.00
Summary
Cardiovascular diseases kill an Australian every 11 minutes. The goal of this proposal is to characterize the role of the conserved heart regulators in cardiac function and disease. Our combined multi-species and informatics approach has identified a major disease locus for sudden cardiac death in humans, which we propose to characterize. This work can lead to new classes of drugs to improve cardiac health and also aid in early diagnosis of patients susceptible to sudden cardiac death.
Underlying Mechanims Of Thalamocortical Dysrhythmia In Chronic Pain
Funder
National Health and Medical Research Council
Funding Amount
$393,817.00
Summary
Pain has a detrimental impact on ones quality of life and a significant financial impact on the community. It has recently been revealed that chronic pain is associated with altered electrical rhythms within the brain. Using human brain imaging, we aim to determine the underlying reason for this altered rhythm in humans with pain resulting from nervous system damage. Defining this mechanism will aid in the development of better treatment regimes.
Substrate Mapping And Ablation Of Ventricular Tachycardia
Funder
National Health and Medical Research Council
Funding Amount
$444,129.00
Summary
Sudden death is a tragic occurrence and can afflict Australians of all ages, racial and ethnic backgrounds. This research will aim to understand abnormalities in the heart muscle that cause dangerous heart rhythm abnormalities, which is the most common cause of sudden death. We will study ways to improve the technology of keyhole cardiac procedures so that it can be used to prevent these arrhythmias from occurring in the first place, and in improving the chance of long-term successful cure.
Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which w ....Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which we have shown to operate in various smooth muscles. This mechanism, termed store-based pacemaking, is entirely different to the currently held cardiac model but could readily achieve the same outcome. We will investigate the hypotheses that this pacemaker mechanism is also fundamental to mammalian heart pacemaking and conduction. Positive support for our hypotheses, as indicated by our findings on amphibian hearts and from pilot findings, may severely challenge the present model for cardiac pacemaking. Such an outcome will have major ramifications on present interpretation of cardiac function in health and disease and will be particularly important to interpretation of disorders associated with cardiac arrhythmias and heart conduction.Read moreRead less
Atrial fibrillation (AF) is the most common cause for an irregular heart beat. Catheter ablation is the only potential cure and involves passing wires via veins in the leg into the heart to deliver discrete small burns(ablation) around the pulmonary veins (PV), the major source for AF. Unfortunately 30-50% of patients have recurrent arrhythmia due to reestablishment of electrical connections. This multicentre internation trial examines whether more (maximal) ablation will improve the outcomes of ....Atrial fibrillation (AF) is the most common cause for an irregular heart beat. Catheter ablation is the only potential cure and involves passing wires via veins in the leg into the heart to deliver discrete small burns(ablation) around the pulmonary veins (PV), the major source for AF. Unfortunately 30-50% of patients have recurrent arrhythmia due to reestablishment of electrical connections. This multicentre internation trial examines whether more (maximal) ablation will improve the outcomes of the procedure.Read moreRead less
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.
Ryanodine Receptor Inhibitors As Therapy For Ca2+ Store Overload Induced Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
This study investigates a new therapeutic action recently discovered for flecainide, an antiarrhythmic agent that we find to completely prevent and inherited form of stress-induced arrhythmias called CPVT. The findings will provide the first detailed mechanistic understanding of an antiarrhythmic drug, findings that will also give a new direction for drug design to control common arrhythmias such as occur in diseases such as coronary artery disease.
Type 2 diabetes is the most common endocrine disease in the world and up to 60% of diabetic patients have heart disease. Heart disease is the most expensive heath condition and biggest cause of death in Australia. Diabetic patients often accumulate fat (triglyceride) within their heart cells, leading to diabetic heart disease. The present study sought to determine if diabetic patients with increased fat within their heart cells have more scarring which eventually results heart muscle dysfunction ....Type 2 diabetes is the most common endocrine disease in the world and up to 60% of diabetic patients have heart disease. Heart disease is the most expensive heath condition and biggest cause of death in Australia. Diabetic patients often accumulate fat (triglyceride) within their heart cells, leading to diabetic heart disease. The present study sought to determine if diabetic patients with increased fat within their heart cells have more scarring which eventually results heart muscle dysfunction.Read moreRead less
Atrial Fibrillation And Hypertension: Reverse Cardiac Remodelling Post Renal Denervation
Funder
National Health and Medical Research Council
Funding Amount
$90,144.00
Summary
Patients with hypertension are at increased risk of heart rhythm disorders, yet little is known if treatment of high blood pressure will improve abnormal rhythm. Renal denervation is a new and effective treatment for severe hypertension; this study will assess the adverse changes in heart structure and function due to severe hypertension, and investigate whether renal denervation can ameliorate these changes on a structural and electrical level.
Genetic Predisposition To Abnormal Atrial Substrate In Atrial Fibrillation (GENE-AF Study)
Funder
National Health and Medical Research Council
Funding Amount
$100,531.00
Summary
Atrial fibrillation (AF) is the most common heart rhythm disorder worldwide and its incidence is growing. Our world-first research aims to demonstrate that individuals who carry specific genetic variants are more likely to develop abnormal electrical and structural changes in the heart, which predispose to AF. In doing so, we intend to find the link between genetics and AF, paving the way for research into novel targeted therapies to better manage this complex and difficult to treat disease.