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
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$606,000.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that c ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that cause severe damage. Further, cells deficient in frataxin are sensitive to oxidant stress and Fe chelators rescue oxidant-mediated death of cells from FA patients. Indeed, free radical scavengers have shown to be of use in the treatment of this disease. Studies in DR's lab during this NHMRC grant have shown that frataxin is down-regulated by erythroid differentiation or the haem precursor, protoporphyrin IX (BLOOD 2002;99:3813-22). These data indicate a role for frataxin in Fe metabolism and the pathogenesis of FA. In this study we will continue to examine the role of frataxin in the way cells handle Fe using experimental models developed under the current NHMRC grant. These include transfected cell lines with low frataxin expression generated using an expression vector containing anti-sense frataxin cDNA. Further we obtained the frataxin conditional KO mouse and generated a breeding colony. These animals display many of the pathological features of FA and are the best current model of the disease. Indeed, they will be critical for assessing the role of frataxin in Fe metabolism and as a model to test the ability of Fe-binding drugs to prevent the pathology observed. We designed lipid-soluble chelators that can enter the mitochondrion to bind Fe (Biochim Biophys Acta 2001;1536:133-140) and these ligands will be tested to prevent disease progression in the KO mice. This exciting research is crucial for understanding the pathogenesis of FA and in creating new therapies.Read moreRead less
THE EFFECT OF STRESS AND ENVIRONMENTAL ENRICHMENT ON DISEASE PROGRESSION IN MESIAL TEMPORAL LOBE EPILEPSY
Funder
National Health and Medical Research Council
Funding Amount
$578,201.00
Summary
Mesial temporal lobe epilepsy, the most common form of drug-resistant epilepsy in adults, is a progressive neurodegenerative condition for which there is currently no effective disease modifying treatment. This proposal will explore whether co-morbid stress accelerates disease progression in MTLE, and whether targeting stress pathways by medical and environmental manipulations can mitigate against this.
Discovery Early Career Researcher Award - Grant ID: DE230100789
Funder
Australian Research Council
Funding Amount
$397,613.00
Summary
Photo-thermal ammonia decomposition . This project aims to develop of novel catalysts targeted to utilise light and heat for the photo-thermal decomposition of ammonia to produce hydrogen and generate new understanding on the role of light in thermal catalytic reactions. The emergence of the hydrogen economy has resulted in the urgent need for safe and efficient hydrogen transport and storage vectors. Ammonia, a hydrogen carrier, is being increasingly considered as a potential key to facilitate ....Photo-thermal ammonia decomposition . This project aims to develop of novel catalysts targeted to utilise light and heat for the photo-thermal decomposition of ammonia to produce hydrogen and generate new understanding on the role of light in thermal catalytic reactions. The emergence of the hydrogen economy has resulted in the urgent need for safe and efficient hydrogen transport and storage vectors. Ammonia, a hydrogen carrier, is being increasingly considered as a potential key to facilitate the hydrogen economy due to its relative ease of storage. The development of catalysts tailored toward capturing light for ammonia decomposition will enable a new potential pathway for the hydrogen economy, with ammonia as a hydrogen vector. Read moreRead less
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.
Intervalence Transfer in Dinuclear and Oligonuclear Polymetallic Assemblies. Mixed-valence compounds (such as the pigment Prussian Blue) have been known for over two centuries, and possess important conductivity, magnetic and spectral properties. Electron transfer between the elements of different valency (intervalence charge transfer, IVCT) gives rise to absorbances in the red or near-infrared region of the spectrum which provide fundamental information on the electron migration. By design of ....Intervalence Transfer in Dinuclear and Oligonuclear Polymetallic Assemblies. Mixed-valence compounds (such as the pigment Prussian Blue) have been known for over two centuries, and possess important conductivity, magnetic and spectral properties. Electron transfer between the elements of different valency (intervalence charge transfer, IVCT) gives rise to absorbances in the red or near-infrared region of the spectrum which provide fundamental information on the electron migration. By design of target di- and higher nuclearity polymetallic species, the project will study IVCT phenomena to understand electron movement, allowing rational development of applicable materials such as catalysts, light-activated devices and non-linear optical materials.Read moreRead less
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
Does Obesity Have The Characteristics Of Addiction?
Funder
National Health and Medical Research Council
Funding Amount
$430,832.00
Summary
The number of overweight or obese people in Australia has increased dramatically in recent years, increasing disease risk. The brain responds to palatable food in ways similar to the response to drugs of addiction, and this may explain why people find it hard to resist palatable food. Our work will explore whether obesity in rats has the characteristics of addiction by examining bingeing, craving, withdrawal and brain circuits in animals chronically exposed to palatable food.
Structures and Properties of beta-R3M (M = Si, Ge, Sn)- and beta-Chalcogenyl-substituted Carbenium Ions. The benefits of this work are many-fold. The scientific knowledge gained will be invaluable to all scientists working in organic chemistry; mechanistic chemists who will learn from the science, and synthetic organic chemists who can utilise the results when planning strategies for the synthesis of complex drugs. Another major benefit of this research is in the training of young scientists. Th ....Structures and Properties of beta-R3M (M = Si, Ge, Sn)- and beta-Chalcogenyl-substituted Carbenium Ions. The benefits of this work are many-fold. The scientific knowledge gained will be invaluable to all scientists working in organic chemistry; mechanistic chemists who will learn from the science, and synthetic organic chemists who can utilise the results when planning strategies for the synthesis of complex drugs. Another major benefit of this research is in the training of young scientists. The students who work on this proposal gain invaluable experience in many areas of chemistry, ranging from synthetic chemistry to structural chemistry and theoretical chemistry. They will also gain experience in important physical techniques from NMR spectroscopy to X-ray crystallography.Read moreRead less