Dementia Associated To Diabetes: Prevention Through The Modulation Of Cerebrovascular Integrity
Funder
National Health and Medical Research Council
Funding Amount
$719,770.00
Summary
Diabetic insulin resistance is reported to induce cognitive decline and dementia. An accumulating body of evidence suggest that compromised integrity of neurovascular unit and following changes in cerebral lipid homeostasis may be centrally involved in the neurodegeneration and cognitive deficits. Therefore, the project aims to prevent the insulin resistance-associated cognitive impairment by modulating the integrity of cerebrovasculature and lipid homeostasis.
Aboriginal And Non-Aboriginal Women Perpetrators Of Violence: A Trial Of A Prison-based Intervention (Beyond Violence)
Funder
National Health and Medical Research Council
Funding Amount
$1,411,825.00
Summary
The proposed study will be the first of its kind in Australia to test a violence prevention program (Beyond Violence) targeting mental health, substance use and violence among incarcerated female offenders with a history of violence. This research responds to the rapidly escalating imprisonment rates among Aboriginal and non-Aboriginal women (particularly for violent offences), and focuses intervention efforts on improving well-being and decreasing reoffending among this vulnerable group.
Role Of Transition Metal Ions And Redox Activity In The Development Of Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability ....Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability to generate free radicals is controversial. This study will employ a novel, minimally-invasive, technique to assess the nature and quantity of metal ions present in well-defined human and animal lesions at different stages of lesion development. The ability of these metal ions to catalyse free radical formation from components present in the artery wall will also be assessed. The release of these metal ions from the artery wall to added organic molecules will be assessed as this might minimise their potential to cause damage, and provide a possible therapeutic strategy. These studies will therefore provide valuable information as to the significance and role of reactive metal ions in the development of human artery disease and the possible prevention, or minimisation, of such processes.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
Nonlinear spatial and spatiotemporal econometrics: theory with applications. Modern societies like Australia have major challenges in the forecasting, measuring and managing of risks associated with global economic and environmental/climate changes. These tasks require advanced econometric techniques in modelling and forecasting of complex nonlinear spatiotemporal variability in economic and social systems. This project will develop frontier econometric technologies that enable more accurate eco ....Nonlinear spatial and spatiotemporal econometrics: theory with applications. Modern societies like Australia have major challenges in the forecasting, measuring and managing of risks associated with global economic and environmental/climate changes. These tasks require advanced econometric techniques in modelling and forecasting of complex nonlinear spatiotemporal variability in economic and social systems. This project will develop frontier econometric technologies that enable more accurate economic and climate forecasts. The tools produced will provide Australia's scientists and policy-makers with a greater capacity to manage the risks associated with these challenges. A side-benefit of the research will be high-quality publications that enhance the nation's reputation in this cutting edge research.Read moreRead less
Nonlinear Panel Data Econometrics: Theory and Practice. This research addresses the ARC National Research Priorities Goal of 'An Environmentally Sustainable Australia', specifically 'Reducing and capturing emissions in transport and energy generation'. Avoiding, managing, and/or adapting to the climate change impacts is now the most pressing global environmental problem. This project will produce tangible and original insights into policy options for institutional adjustment to future climate ....Nonlinear Panel Data Econometrics: Theory and Practice. This research addresses the ARC National Research Priorities Goal of 'An Environmentally Sustainable Australia', specifically 'Reducing and capturing emissions in transport and energy generation'. Avoiding, managing, and/or adapting to the climate change impacts is now the most pressing global environmental problem. This project will produce tangible and original insights into policy options for institutional adjustment to future climate change in Australia; will provide insight into the scope for positive community behavioural change; and possible transformations in Australian social debate to maximise adaptive capacity. It will also strengthen and produce original conceptual approaches and research methods.Read moreRead less
ARC Financial Integrity Research Network. The integrity of the financial system is constantly under stress because of the development of ever more complex financial instruments, structures and strategies, and the associated research technologies that continues to accelerate worldwide. FIRN's vision is to harness the considerable strengths of Australia's internationally renowned finance, accounting and economics researchers into a research agenda to address issues concerning the integrity of the ....ARC Financial Integrity Research Network. The integrity of the financial system is constantly under stress because of the development of ever more complex financial instruments, structures and strategies, and the associated research technologies that continues to accelerate worldwide. FIRN's vision is to harness the considerable strengths of Australia's internationally renowned finance, accounting and economics researchers into a research agenda to address issues concerning the integrity of the financial system. It will enable Australian research in this area to match the scale and impact of similar research in other major international financial centres, and play an essential role in placing Australia among the world's leaders in financial markets related research.Read moreRead less
Melanoma Mutation Profiling For Personalised Treatment
Funder
National Health and Medical Research Council
Funding Amount
$571,191.00
Summary
Melanoma is an aggressive skin cancer, and the leading cause of skin cancer related deaths. Disease spread is difficult to detect and extremely difficult to cure. This bleak clinical outcome is changing with the development of personalised therapies which include small molecule inhibitors to treat metastatic melanoma. Here we seek to identify the spectrum of mutations in patient tumours and circulating tumour cells for advanced personalised treatment.
Identifying Glaucoma Risk Variants In The Norfolk Island Genetic Isolate
Funder
National Health and Medical Research Council
Funding Amount
$658,447.00
Summary
Primary open angle glaucoma is the most common form of glaucoma. In this project we will focus on the identification of functional genetic variants influencing development of this disorder, using a powerful whole exome sequencing approach in a large multigenerational pedigree from the Norfolk Island population isolate. The identification of genes influencing glaucoma development would provide invaluable clues to aid in defining the pathophysiology of this common disease.