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Genomics Of Antiepileptic Drug-induced Stevens Johnson Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$500,817.00
Summary
Epilepsy affects 3% of people. Severe skin reactions to anti-epileptic drugs are unpredictable and potentially fatal. This project aims to better understand the complex genetic architecture of these reactions using the latest sequencing platforms applied to a unique collection of samples, followed by functional analysis. The findings will enhance the practice of precision medicine in epilepsy treatment, shed light on the mechanisms of these reactions, and inform better drug design in the future.
Expression And Regulation Of Human Genes Central To Drug Disposition In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$339,375.00
Summary
The study of the regulation of human genes is inherently difficult. It is difficult or impossible to gain access to many body tissues in either healthy or sick individuals to examine coordinated gene function (or dysfunction). This is particularly true for the brain, where live human tissue is unavailable. For this reason, it is often the case that we have a much better understanding of gene function in species such as rats and mice, the most common animal environments for biomedical research. H ....The study of the regulation of human genes is inherently difficult. It is difficult or impossible to gain access to many body tissues in either healthy or sick individuals to examine coordinated gene function (or dysfunction). This is particularly true for the brain, where live human tissue is unavailable. For this reason, it is often the case that we have a much better understanding of gene function in species such as rats and mice, the most common animal environments for biomedical research. However, findings in animals often fail to meaningfully mirror what occurs in man. To progress our understanding of human genes in brain we need to develop models that more faithfully reproduce the human situation in an environment that is amenable to both manipulation and close examination, such as the novel 'humanized' mouse models described in this application. This application deals with the genes that control enzymes belonging to the human cytochrome P450 3A (CYP3A) subfamily and the drug transporter MDR1. These genes are present in several tissues including liver, gut, lung and brain. They form the main disposal pathway for foreign chemicals such as drugs, environmental pollutants and some cancer causing chemicals. In addition they are involved in the breakdown of several important internally produced substances, such as steroid hormones. We postulate that altered formation of CYP3A enzymes and MDR1 in brain can have a dramatic impact on the action of many important drugs and may affect the way the brain responds in a behavioral sense to hormones, such as sex steroids. In addition, this work will provide a new and useful information relevant to the design and development of the plethora of drugs that act on the central nervous system.Read moreRead less
A Case Control Study Investigating Factors Contributing To The Risk Of Bleeding In Patients Receiving Warfarin Therapy
Funder
National Health and Medical Research Council
Funding Amount
$572,242.00
Summary
Warfarin is a drug commonly used in the elderly to prevent blood clots. Blood clots can lead to stroke. While a very effective drug, it is also a dangerous drug because it can lead to thin blood which makes it more likely that they will bleed. For this reason, the drug should be closely monitored. We know that many people do suffer catastrophic bleeds because the blood is too thin directly as a result of taking warfarin. Some of the reasons for these bleeds are well known; they may be taking dru ....Warfarin is a drug commonly used in the elderly to prevent blood clots. Blood clots can lead to stroke. While a very effective drug, it is also a dangerous drug because it can lead to thin blood which makes it more likely that they will bleed. For this reason, the drug should be closely monitored. We know that many people do suffer catastrophic bleeds because the blood is too thin directly as a result of taking warfarin. Some of the reasons for these bleeds are well known; they may be taking drugs that interact with warfarin, they may have problems with their liver or kidney which affects the body's ability to get rid of it, they may have suffered a fall, to name a few. Studies done overseas have suggested that people are more likely to have a bleed if they do not know how to properly manage their tablets, if they are depressed, if they have no helpers to support them or if their care is not well organised. In Australia, we do not know what impact the organisation of care has on whether a person's warfarin is well managed. We do not know the impact that depression has on their care, or whether people are more likely to have pooorly controlled warfarin if they have few community ties. These are importnat questions to answer, so that we can make significant inroads into preventing death and disability from warfarin.Read moreRead less
Population-level Vaccine Safety Monitoring: Risk Assessment And Policy Implications
Funder
National Health and Medical Research Council
Funding Amount
$85,649.00
Summary
Vaccines prevent millions of deaths worldwide but events can occur after vaccination which may or may not be related to the vaccine. It is vital to ensure vaccines are safe and that both the public and medical providers remain confident in vaccination programs. The PhD thesis will look at the various methods for monitoring vaccine safety in Australia, and compare the usefulness of each system. This will provide information for policy makers on the safety of vaccines in Australia.
Pharmacogenomics And Mechanistic Basis Of Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$677,220.00
Summary
Drug allergy causes physical harm, anxiety and may limit treatment options. We introduced personalised genetic testing to prevent one such drug hypersensitivity. Genetic information from patients who have had adverse drug reactions will be used to work out how drugs trigger severe allergic reactions and develop strategies to predict these reactions and design safer drugs. This research has relevance to our understanding of other inflammatory disease such as autoimmune disease and multiple sclero ....Drug allergy causes physical harm, anxiety and may limit treatment options. We introduced personalised genetic testing to prevent one such drug hypersensitivity. Genetic information from patients who have had adverse drug reactions will be used to work out how drugs trigger severe allergic reactions and develop strategies to predict these reactions and design safer drugs. This research has relevance to our understanding of other inflammatory disease such as autoimmune disease and multiple sclerosis.Read moreRead less
Characterisation Of T-cell Responses In Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$306,338.00
Summary
Drug hypersensitivity reactions (DIHS) are a catastrophic form of adverse drug reaction. This study will use the drug abacavir, a cause of drug hypersensitivity to examine the way certain immune cells react and determine whether responses to viruses that are persistent in our bodies play a role these development of these reactions. This will help inform the immunological basis of DIHS as well as new treatments and potential ways of identifying drugs likely to cause these reactions in the pre-mar ....Drug hypersensitivity reactions (DIHS) are a catastrophic form of adverse drug reaction. This study will use the drug abacavir, a cause of drug hypersensitivity to examine the way certain immune cells react and determine whether responses to viruses that are persistent in our bodies play a role these development of these reactions. This will help inform the immunological basis of DIHS as well as new treatments and potential ways of identifying drugs likely to cause these reactions in the pre-marketing phase of drug development.Read moreRead less
Centre Of Research Excellence In Post-market Surveillance Of Medicines And Medical Devices’
Funder
National Health and Medical Research Council
Funding Amount
$2,500,001.00
Summary
Medicines & medical devices constitute a significant cost to Australia’s health care system. Adverse events resulting from their use are similarly a significant expense that could be reduced by the development of Australia's capacity to use linked health data-sets to detect & monitor adverse events. This Centre aims to develop capacity, methods, knowledge & tools to enhance post-marketing surveillance systems to improve information on medicine & device safety, effectiveness & utilisation.
Deprescribing In Frail Older People: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$269,235.00
Summary
Frail older people are often prescribed unnecessary medications. We will test whether stopping some of their medication improves longevity, sleep quality and independence and reduces confusion and falls. We will stop medication that does not provide any overall benefit or is thought to be harmful in older people. We will monitor our volunteers frequently for adverse effects and re-start their medicines if necessary. We hope to show that it is safe to stop many medications in frail older people.