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C-Jun N-terminal Kinase Actions In The Response To Stress
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
All cells in our body sense and respond to stressful changes in our environment. We are focused on enzymes called JNKs that relay this information, and so form part of the key response pathways. JNKs are now being evaluated as new drug targets for the treatment of diseases including diabetes and stroke, but we know very little about how JNKs work in stressed cells. We will define new partners for the JNKs and in so doing reveal new information on the stress-activated events they regulate.
Increased Vulnerability To Stress During Opiate Dependence: Molecular, Anatomical, And Behavioural Correlates
Funder
National Health and Medical Research Council
Funding Amount
$272,640.00
Summary
Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. It is a chronically relapsing condition for which few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive some individuals to start using heroin, s ....Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. It is a chronically relapsing condition for which few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive some individuals to start using heroin, stress increases the pleasurable effects of heroin and stress increases the aversive effects of heroin withdrawal. These effects will encourage addiction and discourage addicts from seeking treatment. Stress can also cause an otherwise drug-free individual to relapse to heroin addiction despite having been drug-free for some time. In this project we will study why stress has such a large impact on heroin addicts and heroin addiction. We will test the hypothesis that heroin use actually produces profound alterations in the neural network in the brain which controls responses to stress. This project uses a simple animal model of heroin addiction whereby rats are injected with morphine to study the regulation of several genes which are important in responding to stress. We will also study how this exposure and changes in gene expression alter neurobiological, cardiovascular, and behavioural responses to stress. This project will identify parts of the brain that are altered during heroin addiction, and will also identify why heroin addicts are more vulnerable to stress than the general population. Therefore, this project will help us to identify targets for therapeutic intervention (both psychological and pharmacological) and possibly disrupt the addictive cycle.Read moreRead less
Inhibition Of Fear Memories By Extinction: Neural Substrates.
Funder
National Health and Medical Research Council
Funding Amount
$234,250.00
Summary
Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relati ....Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relatively little is known about the mechanisms by which fear memories can be inhibited or suppressed. Understanding this latter process is a key to the development of effective treatments for anxiety disorders such as PTSD where the patient suffers from persistent, intrusive, unwanted trauma memories. A common experimental procedure for reducing learned fear is to repeatedly expose the subject to a fear-eliciting stimulus but without any aversive outcome. This procedure leads to a progressive loss, or extinction, of the fear reactions elicited by the stimulus. Historically, the extinction of fear was thought to be due to an erasure of the fear memory. However, recent evidence shows that extinction inhibits, rather than erases, the fear memory. Because the fear memories remain intact, some structure(s) in the brain must inhibit activity in the fear pathway. This project uses extinction of conditioned fear reactions in rat subjects to determine the structure(s) in the brain that inhibit fear memories and their behavioural and cardiovascular expression. It brings together the expertise of four well-established researchers and uses a combination of behavioural, physiological, immunohistochemical, tract tracing, and lesion approaches to achieve this aim. The proposed experiments will reveal the structure(s) in the brain that control the inhibition of fear, as well as the site(s) of this inhibition in the fear pathwayRead moreRead less
A Prospective Study Of Traumatic Stress In Children Involved In Motor Vehicle Accidents
Funder
National Health and Medical Research Council
Funding Amount
$185,889.00
Summary
Motor vehicle accidents (MVAs) are relatively frequent major life trauma that represent significant life threatening experiences. Not surprisingly evidence suggests that MVAs represent a frequent trigger for the development of post traumatic stress disorder (PTSD), although studies have typically focussed upon adult survivors. Local statistics indicate a significant proportion of children will experience a MVA of sufficient severity to warrant attendance at hospital. This project is of significa ....Motor vehicle accidents (MVAs) are relatively frequent major life trauma that represent significant life threatening experiences. Not surprisingly evidence suggests that MVAs represent a frequent trigger for the development of post traumatic stress disorder (PTSD), although studies have typically focussed upon adult survivors. Local statistics indicate a significant proportion of children will experience a MVA of sufficient severity to warrant attendance at hospital. This project is of significance because it will provide badly needed information about the prevalence and course of emotional and behavioural problems in children following exposure to a serious MVA. More broadly the study should provide valuable information on post-traumatic stress responses in children. Furthermore, it will enable us to identify the factors that place children at particular risk of developing psychological problems following a MVA. This will provide information to help design of interventions to prevent the development of PTSD and other forms of psychopathology following MVAs. Such data will also permit identification of those children who are at particular risk of psychological morbidity after MVA trauma and for whom preventive interventions are most likely to be beneficial.Read moreRead less
Role Of HtrA And RseP, Stress Response Proteases, In Development And Persistence Of Chlamydia Trachomatis Infections
Funder
National Health and Medical Research Council
Funding Amount
$389,984.00
Summary
This project will research the most commonly reported bacterial sexually transmitted infection Chlamydia trachomatis. Bacterial proteins which could play a role in chronic infections of humans will be investigated. Proteins will be biologically examined to determine their role during disease. This may identify proteins which could be used for diagnostic and therapeutic tools to prevent chronic Chlamydia infection (which can result in infertility and other serious conditions).
Cognitive Impairments And Post Traumatic Stress Symptoms In Children With Traumatic Brain Injury: A Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$482,250.00
Summary
Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic ....Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic stress, it is not clear how these interact, how they influence long-term outcomes, and what factors such as pre-injury functioning and family support and distress mediate outcomes. These issues are very important since effective rehabilitation of children following traumatic brain injury is essential to maximise long-term functioning and minimise disability. To be effective, rehabilitation must be guided by the knowledge about key factors that determine the recovery process. This study aims to provide answers to these questions by following two cohorts of children (aged 6-14) over 18 months after receiving a traumatic brain injury. In total 240 children will be recruited from Brisbane and Melbourne hospitals. They will be assessed at three, six, twelve and eighteen months post-injury using measures of cognitive, psychological and social functioning. Information on parent distress and behaviours will also be obtained. The information obtained will provide the basis for the development of a specific rehabilitation strategy for children with traumatic brain injury, including information on strategies to help prevent any confounding impact of post-traumatic stress on recovery.Read moreRead less
Neurobiological Causes Of Overeating In A Rodent Model - Hedonic Versus Homeostatic Control
Funder
National Health and Medical Research Council
Funding Amount
$431,215.00
Summary
Unlimited access to palatable high fat foods, in conjunction with a sedentary life style, has led to increased obesity. Exactly what mechanisms drive over consumption of energy rich foods and override mechanisms that normally regulate body weight? This project will examine feeding behaviour in rats fed palatable high fat diet, to examine when and how they eat. The contribution of brain chemicals implicated in addiction to this eating, and the impact of withdrawal of food will be examined.
The Effect Of Stress And Hypercortisolaemia On Limbic Epileptogenesis & Affective Disorder.
Funder
National Health and Medical Research Council
Funding Amount
$380,714.00
Summary
This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is ....This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is a bi-directional relationship, with the psychiatric conditions and stress also acting to aggravate the seizures and even predispose to the development of the epilepsy itself. Apart from gaining insights into causes of TLE, anxiety and depression, this framework has potential public health relevance suggesting approaches to the eventual primary and secondary prevention of both MTLE and its associated psychiatric co-morbidities, a neglected area at present. The use of an animal model allows investigation of aetiological processes that extend over the lifetime, which is exceptionally difficult to achieve in humans. Retrospective studies, such as case-control studies, although an indispensable research methods, are subject to bias and imprecision when it comes to measuring remote past exposures to stress, abuse, and deprivation. If the results of these experiments are consistent with our hypotheses, a very strong case would exist for exploring this relationship in human studies. The data would also provide a strong rationale for more aggressive detection and treatment of these psychiatric co-morbidities in TLE patients, in order to potentially modify the progression of the disorder as well as improve the quality of life of sufferers. The results of intervention studies in animal models may suggest specific mode of treatment to achieve this.Read moreRead less
Assessment Of Oxidant Stress And Mitochondrial Dysfunction In Young Adults With Iron Loading Diseases
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Disorders of iron metabolism are particularly prevalent in Australia and the consequences of excess iron can be severe. Liver disease is frequently associated with iron loading. The commonest form of iron loading can be treated readily, but it is unclear when the first signs of tissue damage occur and thus at what stage treatment should commence. This project will examine in detail the relationship between body iron levels and signs of tissue damage in young subjects with iron loading disease.
Why Does Early Life Stress Aggravate Limbic Epileptogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$540,116.00
Summary
High rates of anxiety and depression occur in individuals with temporal lobe epilepsy (TLE), the most common form of focal epilepsy in adults. Rats that have experienced early life stress show increased anxiety, decreased seizure thresholds and accelerated epilepsy as adults. We have important leads to mechanisms. The proposed study will better understand the mechanisms connecting early life stress and psychiatric disease to adult TLE, and to test interventions that may counteract these effects.