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.
Unravelling The Mechanism Of MHC Class-I Associated Drug Hypersensitivities
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Some drugs cause adverse reactions that are life threatening. We think these reactions are mediated by killer T cells as they are genetically controlled by immune response genes that normally guide immunity to microbes. We will study immune reactions to the drug abacavir, used to treat HIV (AIDS); allopurinol used to prevent gout and carbamazepine, used to treat epilepsy. The study may also help devise better treatments for patients who experience severe forms of these reactions.
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
Innovative approaches to understanding and limiting the public health risks of Cryptosporidium and Giardia in animals in Australian catchments. Sophisticated molecular typing and modelling will be used to determine if chlorine-resistant parasites in animals in catchments are responsible for infection in humans. Improved catchment management and risk mitigation strategies will be developed during this project, which will make a substantial contribution to the provision of safe drinking water acro ....Innovative approaches to understanding and limiting the public health risks of Cryptosporidium and Giardia in animals in Australian catchments. Sophisticated molecular typing and modelling will be used to determine if chlorine-resistant parasites in animals in catchments are responsible for infection in humans. Improved catchment management and risk mitigation strategies will be developed during this project, which will make a substantial contribution to the provision of safe drinking water across Australia.Read moreRead less
Troublesome ticks: a new molecular toolkit to investigate zoonotic tick-borne pathogens in Australia. This project will use the latest molecular diagnostic techniques to address unanswered questions about potential tick-transmitted diseases of humans and companion animals in Australia. The study will identify 'hot-spots' for tick-borne pathogens, identify areas of potential risk for humans, and investigate vector-host-pathogen interactions nationwide.
Ecology and transmission of tick-borne disease in Australia. Ecology and transmission of tick-borne disease in Australia. This project aims to determine the bacterial, protozoal and viral biodiversity in wildlife ticks and their native mammal hosts, and provide new information about the biology and transmission dynamics of these microorganisms and their potential to cause disease in wildlife, domesticated animals and humans. Anticipated outcomes are improved diagnostic tests and management proto ....Ecology and transmission of tick-borne disease in Australia. Ecology and transmission of tick-borne disease in Australia. This project aims to determine the bacterial, protozoal and viral biodiversity in wildlife ticks and their native mammal hosts, and provide new information about the biology and transmission dynamics of these microorganisms and their potential to cause disease in wildlife, domesticated animals and humans. Anticipated outcomes are improved diagnostic tests and management protocols for tick-borne disease in Australia.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100635
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Demographic distribution models for ecology, conservation & public health. This project aims to advance distribution modelling by developing a new demographic species distribution modelling (DSDM) framework that unites correlative and process-based approaches. This project will develop ecologically realistic models of the distributions of species and diseases, leading to better decision-making in conservation and public health. This will provide significant benefits, such as a better understandi ....Demographic distribution models for ecology, conservation & public health. This project aims to advance distribution modelling by developing a new demographic species distribution modelling (DSDM) framework that unites correlative and process-based approaches. This project will develop ecologically realistic models of the distributions of species and diseases, leading to better decision-making in conservation and public health. This will provide significant benefits, such as a better understanding of where and how to control mosquitoes to reduce malaria transmission in Africa, how best to conserve the vulnerable greater glider in Eastern Australia, and to forecast where and when outbreaks of Ross River virus are likely occur in Victoria.Read moreRead less