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A Randomised Controlled Trial Of A Promising New Treatment For Chronic Whiplash
Funder
National Health and Medical Research Council
Funding Amount
$620,556.00
Summary
Following a whiplash injury about one third of people develop persisting pain and disability i.e. chronic whiplash. In a series of pilot trials we have developed a new physiotherapy treatment for chronic whiplash. Initial results are very promising. We now propose to definitively establish the effectiveness of this new treatment in a large clinical trial. At the same time we will evaluate the cost-effectiveness of the treatment.
Combined Dry-needling, Advice And Graded Exercise: A Randomized Controlled Trial In Chronic Whiplash
Funder
National Health and Medical Research Council
Funding Amount
$309,339.00
Summary
Central hyperexcitability is a feature of chronic whiplash and may be one reason for the poor response of this condition to standard treatment approaches such as exercise. Complementary and Alternative Medicine (CAM) treatment of dry-needling has shown potential to decrease this hypersensitivity in other musculoskeletal conditions. This study will investigate the effects of dry-needling combined with an orthodox treatment of advice and graded exercise on pain and disability in chronic whiplash.
Effective Management Of Acute Whiplash Injuries Requires A Pragmatic Approach: An RCT With Stratified Treatments
Funder
National Health and Medical Research Council
Funding Amount
$382,550.00
Summary
Whiplash injuries from a motor vehicle crash continue to incur substantial personal and financial costs to the community and the insurance industry. The current approaches to an acute whiplash injury in Australia and internationally have failed to lessen the rate of how many people develop chronic neck pain. Between 40 and 60% still have pain 6 months after injury. Motor Accident Insurance Commission (Qld) figures indicate that 20% of patients with chronic whiplash account for 60% of the costs. ....Whiplash injuries from a motor vehicle crash continue to incur substantial personal and financial costs to the community and the insurance industry. The current approaches to an acute whiplash injury in Australia and internationally have failed to lessen the rate of how many people develop chronic neck pain. Between 40 and 60% still have pain 6 months after injury. Motor Accident Insurance Commission (Qld) figures indicate that 20% of patients with chronic whiplash account for 60% of the costs. Transition from an acute to a chronic condition must be prevented. A new direction in management in the acute stage is urgently required as once the pain has become chronic, it is difficult to help. This research will conduct a novel randomised controlled trial for acute whiplash. It will test individually prescribed multi-professional management against usual care with the aim to lessen the numbers who go on to develop chronic pain. It will be the first clinical trial that acknowledges from the outset that the whiplash injuries and affects people in different ways. Our previous research with acute whiplash patients has documented the variations in presentation from physical, physiological and psychological perspectives. In this trial, management will be prescribed as directed by measurable pain, muscle and psychological impairments in the individual, rather than regard all patients as the same as in other trials. This trial will offer individualised treatments; medical, physiotherapy and-or psychological using an empirically derived treatment algorithm. Cost-effectiveness of the program will be evaluated against that incurred during usual care. It is predicted that early multi-professional management will be less expensive in the long term than existing approaches. This RCT stands to extend knowledge in the management of whiplash associated disorders (WAD).Read moreRead less
Therapeutic Implications Of A Molecular Link Between Survivin And Telomerase Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
A unifying feature of all types of cancer cells is that they are immortal. Our investigations will build upon our recent results that showed the gene survivin is involved in cancer cell immortalisation. We will characterise a molecular link between survivin and the enzyme telomerase, which is central to cancer cell immortality. Furthermore, we will demonstrate the therapeutic potential of turning off both survivin and telomerase as a novel approach to halting the growth of cancer cells.
The Nuclear Growth Hormone Receptor- Its Actions And Mechanism Of Nuclear Translocation
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
We and others have found that cell surface receptors for growth factors such as EGF, FGF and growth hormone can be found in the nucleus of proliferating cells. We have shown that many cancers have elevated nuclear GH receptor including leukemia, breast and colon cancer. If we artificially target the GH receptor to the nucleus, the resulting cells are tumorigenic when injected into immunocompromised mice, rapidly form ing metastasising tumours. To create more effective inhibitors of this tumourog ....We and others have found that cell surface receptors for growth factors such as EGF, FGF and growth hormone can be found in the nucleus of proliferating cells. We have shown that many cancers have elevated nuclear GH receptor including leukemia, breast and colon cancer. If we artificially target the GH receptor to the nucleus, the resulting cells are tumorigenic when injected into immunocompromised mice, rapidly form ing metastasising tumours. To create more effective inhibitors of this tumourogenesis, and to define the physiological roles of nuclear GH receptor, we will define the transport process which carries the receptor to the nucleus and block it. We will also seek to define how the receptor in the nucleus interacts directly with DNA to inhibit programmed cell death. To carry out these projects we will use sophisticated proteomics -mass spectrometry to identify the proteins interacting with the receptor in the transport and gene activation processes. The role of candidates will be tested by preventing their expression or by direct inhibition of their action using drugs or dominant negative versions. These approaches will provide leads to new anti-cancer therapeutics, and therapies for blocking diabetic blindness and kidney failure.Read moreRead less
Life Course Trajectories And Neuropsychiatric Outcomes In An E-cohort Of High Risk Children Of Mothers With Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$796,484.00
Summary
This study investigates how genetic and environment factors operate over the life course to increase risk of adverse outcomes for children of women with severe mental illness. We examine the clustering of neuropsychiatric outcomes in families and individuals, the role of developmental adverse life events in the risk for these outcomes, and the children's physical morbidity and offending profiles. This is an electronic cohort (e-cohort), constructed by record linkage across many databases.
Detection Of Alternative Lengthening Of Telomeres In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
In each cell, DNA is packaged into units called chromosomes, the ends of which (i.e., telomeres) become slightly shorter every time they are replicated during the production of new cells. Continued cell replication and hence continued telomere shortening eventually results in the inability of cells to replicate themselves any further. Normal cells have mechanisms to slow down, but not completely prevent telomere shortening. The development of a cancer depends on its cells being able to replicate ....In each cell, DNA is packaged into units called chromosomes, the ends of which (i.e., telomeres) become slightly shorter every time they are replicated during the production of new cells. Continued cell replication and hence continued telomere shortening eventually results in the inability of cells to replicate themselves any further. Normal cells have mechanisms to slow down, but not completely prevent telomere shortening. The development of a cancer depends on its cells being able to replicate themselves many times, and therefore they need to find a method to prevent their telomeres shortening. We discovered one such method, called Alternative Lengthening of Telomeres (ALT), that is used by some cancers. It has been shown in principle that cancer cells can be killed by disrupting their ability to prevent telomere shortening. Therefore, in another project we are developing methods needed to find drugs that inhibit ALT. In the meantime, we have found the first evidence that some normal cells have an ALT-like mechanism. Our speculation is that cancer cells are able to dysregulate and subvert this normal mechanism in order to prevent their telomeres from shortening. In this project, we will analyse the ALT-like mechanism in mice, to determine its characteristics, and to determine what tissues use it. This information will provide critically important insights into the ALT mechanism itself, and the likely side effects of drugs that inhibit ALT.Read moreRead less
Infectious Large Capacity Vectors For Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$374,625.00
Summary
The next 25 to 50 years will witness the culmination of a demographic shift in the age of the population which will be associated with an increasing importance of both inherited predispositions to late-onset chronic, complex diseases and natural degenerative processes. Medicine has historically sought to manage and cure the symptoms of disease. The focus for therapy has begun to switch from alleviating the ailments to establishing and resolving their causes. On the back of the Human Genome Proje ....The next 25 to 50 years will witness the culmination of a demographic shift in the age of the population which will be associated with an increasing importance of both inherited predispositions to late-onset chronic, complex diseases and natural degenerative processes. Medicine has historically sought to manage and cure the symptoms of disease. The focus for therapy has begun to switch from alleviating the ailments to establishing and resolving their causes. On the back of the Human Genome Project, genetics research will identify genes that are central to these processes, leading to gene-based medicine. Some of this new treatment will be drug-based but an alternative is the correction of the defective genes themselves gene therapy to either replace inherited faulty genes or to provide novel or modified genes that may help the repair and maintenance of tissue, or combat abnormal processes such as cancer. Gene therapy is a field still in its infancy with just a few qualified successes reported in the past few years. Persistent expression of a transgene at therapeutic levels is required for successful gene therapy. Most of the currently used vector and virus systems have a small capacity and usually employ a reduced (cDNA) copy of the transgene lacking natural control mechanisms. These are prone to vector loss and promiscuous expression or loss of expression. The delivery of genomic DNA up to 20 times this size would enable genes to be transferred in entirety, including their natural regulatory elements. This project aims to develop a vector system based on Herpesviruses that tackles some of the problems with the current generation of gene therapy vectors. This system is particularly aimed at providing long-term gene expresssion at physiological levels and safe, efficient delivery systems through the use of genomic DNA.Read moreRead less
Brain And Skin Blood Flow: New Animal Model For Understanding Psychiatric Disorders And Evaluating Psychotropic Agents
Funder
National Health and Medical Research Council
Funding Amount
$874,840.00
Summary
We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major brain pathway by which the constrict-the-skin-bloo ....We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major brain pathway by which the constrict-the-skin-blood-vessels message reaches the spinal cord. The pathway involves the amygdala, a forebrain region important in emotional expression and the raphe nuclei in the medulla oblongata. Drugs which affect psychological function also effect skin blood flow. Ecstasy, the street drug used to induce euphoria also constricts the skin vessels, and, sadly, the body temperature may increase so much that death ensues. Ecstasy vigorously constricts the skin blood vessels in rabbits, and temperature increases. Ecstasy is thought to act on serotonin-containing nerve cells in the brain, releasing serotonin (5-HT) onto special 5-HT2A receptors. Activation of these receptors affects both psychological function and skin blood flow. Modern drugs used to treat schizophrenia, so called atypical antipsychotics like clozapine and olanzapine, are thought to act as antagonists at 5-HT2A receptors in the brain. We were thus very excited when we discovered in our rabbit model that clozapine reverses the skin vasoconstriction induced by ecstasy. This means that we have specific hypotheses concerning the actual brain pathways and neurotransmitters whereby ecstasy and clozapine exert their effects on skin blood flow. Elucidating these pathways in rabbits and rats will provide solid knowledge concerning the mechanism of action of the atypical antipsychotics, and it may well prove possible to use our animal model to predict whether proposed new antipsychotic agents will be therapeutically effective.Read moreRead less
Normal organ development and many disease processes, such as cancer and tissue damage, depend upon formation of new blood vessels. Our research seeks to identify novel factors regulating blood vessel growth. In this context we have examined the role of proteins that mediate communication between cells, called connexins. By increasing our understanding of the factors affecting blood vessel growth we learn how to create novel therapies to enhance the treatment of ischemic disease and cancer.