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Dynamic Action Potential Clamp Studies Of Drugs That Affect The Cardiac Action Potential
Funder
National Health and Medical Research Council
Funding Amount
$343,976.00
Summary
The development of drugs to treat and.or prevent cardiac arrhythmias have been plagued by the side-effect of actually increasing the risk of sudden death. One of the reasons for this is that drugs that work well in one part of the heart may cause problems in another part. We are developing a system called “dynamic action potential clamp” that will make it easier for researchers to assess the effect of drugs in different regions of both normal and diseased hearts.
Role Of Calcium-activated Potassium Channels In Neuronal Excitability, Synaptic Plasticity And Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$612,272.00
Summary
Disturbances in brain function, as occur in diseases such as epilepsy and schizophrenia, are associated with abnormal electrical activity. This electrical activity leads to increases in calcium inside nerve cells. In this project we plan to investigate how changes in calcium inside nerve cells regulates electrical activity, and how this impacts on the capacity of the brain to process and learn new information.
Oxidative Regulation Of The Na Pump- A New Player In Vascular Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$504,427.00
Summary
Oxidative stress is a major player in hypertension, atherosclerosis, diabetes and ageing, but we have struggled to develop a therapy to successfully combat in heart and vascular cells in large clinical trials. We have discovered a new role for membrane protein FXYD1, to protect key heart and vascular proteins from functional impairment secondary to oxidative stress. We will investigate its role in protecting against vascular disease, and test novel therapies based on this endogenous protector.
Anthracyclines Disrupt Ca2+ Signalling In Cardiomyocytes: A Contribution To Cardiac Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$525,620.00
Summary
Anthracyclines are one of the most effective drugs used in chemotherapy, but cause side effects resulting in serious heart problems which can be fatal. The link between anthracycline therapy and the problems they cause in the heart is not fully defined. We will investigate mechanisms leading to these side effects and define specific targets of anthracyclines in the heart. It is hoped this will lead to the design of new drugs which counteract the side effects of anthracycline treatment.
How Does Sudden Cardiac Death Occur In Familial Hypertrophic Cardiomyopathy?
Funder
National Health and Medical Research Council
Funding Amount
$1,312,606.00
Summary
Familial hypertrophic cardiomyopathy is a leading cause of sudden cardiac death but the mechanisms for the induction of arrhythmia are unknown. This proposal has the potential to impact sudden death in the young and enable significant expansion of Australia’s research capacity into the treatment of familial hypertrophic heart disease in humans.
Failure-to-progress In Human Labour Results From A Profound Electrical Negativity Of The Uterine Cells: Targeting The Ion Channels Involved
Funder
National Health and Medical Research Council
Funding Amount
$564,541.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems to lay the foundations for better therapeutics.
Understanding Uterine Contractility: What Can We Learn From Obesity?
Funder
National Health and Medical Research Council
Funding Amount
$600,792.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified five dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems, particularly those mechanisms in common.
New CaMKII Therapeutic Targets In Heart Failure With Preserved Ejection Fraction
Funder
National Health and Medical Research Council
Funding Amount
$740,335.00
Summary
Deaths associated with impaired heart muscle relaxation and unstable cardiac cycle rhythm are increasing. The mechanisms by which these pathologies occur are not understood and clinical therapies are lacking. We have novel evidence to suggest that a key signalling protein, CaMKII, is critically involved in the development of these forms of heart pathology. This goal of this project is to identify how CaMKII is implicated in heart failure and dysrhythmia as a basis for designing new therapies.
Optimising Efficacy Of A Peptide Derived Against The Alpha-interacting Domain Of The L-type Calcium Channel In Reduction Of Ischemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$405,063.00
Summary
A heart attack is associated with an increase in free radicals and calcium in heart muscle cells. The function of the L-type calcium channel, a protein responsible for calcium entry into cells, is altered by free radicals and this contributes to the development of heart disease. We now have considerable proof of concept that a peptide derived against the L-type calcium channel can decrease heart injury. We will optimise efficacy and delivery of the peptide to prevent heart failure.
Investigating CRAC Channel Assembly And Interactions Important In Immunity
Funder
National Health and Medical Research Council
Funding Amount
$398,247.00
Summary
#ERROR: -Transmission and amplification of signals between subcellular compartments underpins cell function. Calcium ions are cellular messengers that can cross Membranes using specialised pores. CRAC Calcium channels in particular are critical for immune system function,and partner Proteins switch them on and off in a feedback response to compartmental Calcium levels. the objective of my research is to investigate how opening and closing of the CRAC pore is triggered at a molecular level.