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
A Future Beyond the Wall: Improving Post-release Employment Outcomes for People Leaving Prison. Engaging in meaningful work has been shown to reduce re-offending by ex-prisoners, but few prison releasees internationally or in Australia gain employment, and successful pathways to employment for this group are poorly researched and understood. This study aims to gather and analyse, for the first time, comparative data from Australian jurisdictions and employment agencies on the relationship betwee ....A Future Beyond the Wall: Improving Post-release Employment Outcomes for People Leaving Prison. Engaging in meaningful work has been shown to reduce re-offending by ex-prisoners, but few prison releasees internationally or in Australia gain employment, and successful pathways to employment for this group are poorly researched and understood. This study aims to gather and analyse, for the first time, comparative data from Australian jurisdictions and employment agencies on the relationship between in-prison and post-prison vocational education and employment programs, employment and recidivism. It aims to identify effective elements, strategies, program and policy directions in offender training and employment. This is a unique partnership amongst key academics in the field, peak national bodies, correctional and employment organisations.Read moreRead less
Innovations in Clinical Education for Physiotherapy Students. Australia has workforce shortages and an ageing population. Physiotherapists are key players in promoting and maintaining good health through their leadership in physical activity and rehabilitation to retain Australians in the workforce and to ensure quality of life for our ageing population. There is a national shortage of physiotherapists. Increasing numbers of physiotherapists are being trained, requiring new models of clinical tr ....Innovations in Clinical Education for Physiotherapy Students. Australia has workforce shortages and an ageing population. Physiotherapists are key players in promoting and maintaining good health through their leadership in physical activity and rehabilitation to retain Australians in the workforce and to ensure quality of life for our ageing population. There is a national shortage of physiotherapists. Increasing numbers of physiotherapists are being trained, requiring new models of clinical training as there is no capacity in conventional training to cope with student numbers. This research will develop and evaluate new models of training incorporating standardised patients (actors) and simulators (mannequins) which increase education capacity. Models are transferable to other health professions.Read moreRead less
A cross-national study of the relative impact of an oral component on PhD examination quality, language and practice. High quality doctoral degrees call for the most effective forms of assessment. This project investigates the role of oral examination in PhD assessment, common internationally but not in Australia, and is the first to compare the relative impact of oral and 'no oral' models on examination quality, language and practice.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100031
Funder
Australian Research Council
Funding Amount
$1,000,000.00
Summary
Expanding our view of the Universe with the Murchison Widefield Array. Expanding our view of the Universe with the Murchison Widefield Array:
This project aims to build a Phase 2 Murchison Widefield Array (MWA) to boost the capabilities of the Phase 1 MWA by an order of magnitude. The Epoch of Reionisation (EoR), when the first stars and galaxies lit up the universe, is the last unstudied phase of cosmic evolution. The MWA is at the frontier of EoR research and all-sky survey astrophysics, is t ....Expanding our view of the Universe with the Murchison Widefield Array. Expanding our view of the Universe with the Murchison Widefield Array:
This project aims to build a Phase 2 Murchison Widefield Array (MWA) to boost the capabilities of the Phase 1 MWA by an order of magnitude. The Epoch of Reionisation (EoR), when the first stars and galaxies lit up the universe, is the last unstudied phase of cosmic evolution. The MWA is at the frontier of EoR research and all-sky survey astrophysics, is the only low frequency precursor for the Square Kilometre Array (SKA), and is the only SKA precursor delivering science quality data. This project to construct a Phase 2 MWA would double the number of antennas in the array, double the maximum baseline length, and boost our all-sky survey and EoR capabilities. Read moreRead less
Reliable and accurate statistical solutions for modern complex data. This project aims to develop novel methods for reliable and accurate statistical modelling with modern, complex correlated and error-prone data. The project expects to make significant strides towards future-proofing statistical data analysis, equipping practitioners with a suite of robust and computationally efficient methods which provide confidence in the stability and reproducibility of results obtained, while offering guar ....Reliable and accurate statistical solutions for modern complex data. This project aims to develop novel methods for reliable and accurate statistical modelling with modern, complex correlated and error-prone data. The project expects to make significant strides towards future-proofing statistical data analysis, equipping practitioners with a suite of robust and computationally efficient methods which provide confidence in the stability and reproducibility of results obtained, while offering guarantees on their transferability over a range of populations. This will provide important benefits as they are applied in predicting endangered marine species for fisheries conservation, and in enhancing our national understanding of the relationship between education achievement and financial success. Read moreRead less
Exploring processes of change in parenting interventions for high-risk parents. This study will identify the timing and triggers of change in parents as they participate over 18 months in an intensive therapeutic parenting program. The findings will inform planners and service providers about the most effective features of such programs to facilitate change in parents at risk of abuse and neglect of their children.
Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown t ....Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown to respond to mechanical stimuli in the same manner as mechanoreceptor channels of organisms from bacteria to humans the intended outcome of this project is to uncover the unifying principles of mechanotransduction anchored in the laws of physics and chemistry that have guided the force-dependent design of all life forms.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC180100024
Funder
Australian Research Council
Funding Amount
$4,000,000.00
Summary
ARC Training Centre for Medical Implant Technologies. The ARC Training Centre for Medical Implant Technologies aims to train a new generation of interdisciplinary engineers and to transform the orthopaedic and maxillofacial implant industry in Australia. In collaboration with industry, universities and hospitals, the Centre will build a dynamic training environment for interdisciplinary engineers to develop and evaluate personalised implants and surgeries. It will create new networks, internatio ....ARC Training Centre for Medical Implant Technologies. The ARC Training Centre for Medical Implant Technologies aims to train a new generation of interdisciplinary engineers and to transform the orthopaedic and maxillofacial implant industry in Australia. In collaboration with industry, universities and hospitals, the Centre will build a dynamic training environment for interdisciplinary engineers to develop and evaluate personalised implants and surgeries. It will create new networks, international collaborations and a generation of industry-ready researchers critical for growing Australia’s industry. The advances in materials and savings in time for procedures will reduce costs.
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