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
WAKE FLOWS WITH UPSTREAM TURBULENCE IN MARINE, ATMOSPHERIC AND BUILT ENVIRONMENTS. Through improved understanding of turbulent wakes the project will have applications across aeronautics and hydrodynamics, leading to more efficient engineering designs to reduce flow drag. In marine environments our findings will improve coastal ocean models and the prediction of pollutant dispersal, nutrient fluxes and sediment transport, and contribute to the management of biological productivity (NRP 1.5). In ....WAKE FLOWS WITH UPSTREAM TURBULENCE IN MARINE, ATMOSPHERIC AND BUILT ENVIRONMENTS. Through improved understanding of turbulent wakes the project will have applications across aeronautics and hydrodynamics, leading to more efficient engineering designs to reduce flow drag. In marine environments our findings will improve coastal ocean models and the prediction of pollutant dispersal, nutrient fluxes and sediment transport, and contribute to the management of biological productivity (NRP 1.5). In the atmospheric boundary layer, the results will assist planners to improve wind environments near large buildings or clusters of buildings, benefiting the safety of aircraft at takeoff and landing. The project will develop collaboration and help maintain the strength of Australian research in environmental flows.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100092
Funder
Australian Research Council
Funding Amount
$389,742.00
Summary
What is extreme? Advancing insights into Australia’s variable rainfall. This project aims to address fundamental questions about the causes of Australia’s rainfall variability, providing crucial information about how changing climates affect the water cycle. Bringing together earth system data from ground-based and satellite observations, palaeoclimate reconstructions and climate model simulations, it plans to analyse the processes that cause change in Australia’s rainfall. The project aims to i ....What is extreme? Advancing insights into Australia’s variable rainfall. This project aims to address fundamental questions about the causes of Australia’s rainfall variability, providing crucial information about how changing climates affect the water cycle. Bringing together earth system data from ground-based and satellite observations, palaeoclimate reconstructions and climate model simulations, it plans to analyse the processes that cause change in Australia’s rainfall. The project aims to integrate these datasets using the novel analysis of water isotopes, an important diagnostic of the water cycle. This approach is expected to help evaluate how Australia’s rainfall responds to natural and anthropogenic drivers and identify the processes behind recently observed rainfall extremes.Read moreRead less
ARC Centre of Excellence for Climate Extremes. This Centre aims to transform understanding of past and present climate extremes and revolutionise Australia’s capability to predict them into the future. Climate extremes cost Australia up to $4 billion a year and will intensify over coming decades. This Centre’s blue-sky research will discover processes that explain the behaviour of present and future climate extremes. It will use its researchers, data, modelling, collaboration, graduate programme ....ARC Centre of Excellence for Climate Extremes. This Centre aims to transform understanding of past and present climate extremes and revolutionise Australia’s capability to predict them into the future. Climate extremes cost Australia up to $4 billion a year and will intensify over coming decades. This Centre’s blue-sky research will discover processes that explain the behaviour of present and future climate extremes. It will use its researchers, data, modelling, collaboration, graduate programme and early career researcher mentoring to transform Australia’s capacity to predict climate extremes. This research is expected to make Australia more resilient to climate extremes and minimise risks from climate extremes to the Australian environment, society and economy.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100040
Funder
Australian Research Council
Funding Amount
$580,000.00
Summary
Fast Disk Storage to Enable Big Data Science in Weather, Oceans and Climate. This project aims to expand Australia's capacity to do high-impact innovative climate, weather and oceanographic science. Science of this kind relies on massive data coupled to computationally highly intensive and complex analysis. Therefore, the project will purchase fast disk storage and install it at the National Computing Infrastructure. It is anticipated that the project will benefit the nation through better under ....Fast Disk Storage to Enable Big Data Science in Weather, Oceans and Climate. This project aims to expand Australia's capacity to do high-impact innovative climate, weather and oceanographic science. Science of this kind relies on massive data coupled to computationally highly intensive and complex analysis. Therefore, the project will purchase fast disk storage and install it at the National Computing Infrastructure. It is anticipated that the project will benefit the nation through better understanding of the climate system, including extremes; improvements in our capacity to make predictions; and through applications of the science to forecasting, the management of resources among other many other things.Read moreRead less
Southern Ocean aerosols: sources, sinks and impact on cloud properties. This project aims to provide fundamental process-level understanding of atmospheric aerosol processes over the Southern Ocean, a region that has a profound influence on the Australian and global climate and where climate models perform poorly. Comprehensive observations during 3 Southern Ocean voyages and land-based measurements will enhance our knowledge of aerosols and cloud formation in that region and provide much-needed ....Southern Ocean aerosols: sources, sinks and impact on cloud properties. This project aims to provide fundamental process-level understanding of atmospheric aerosol processes over the Southern Ocean, a region that has a profound influence on the Australian and global climate and where climate models perform poorly. Comprehensive observations during 3 Southern Ocean voyages and land-based measurements will enhance our knowledge of aerosols and cloud formation in that region and provide much-needed data for improving global climate models. Expected outcomes include more accurate seasonal and latitudinal representations of Southern Ocean aerosol populations, properties and sources. The main benefit includes improvements in weather forecasting and future climate projection for Australia and the Southern Hemisphere.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668448
Funder
Australian Research Council
Funding Amount
$150,000.00
Summary
See Hear! Multimodal Recording and Analysis Facility. High resolution recording and analysis will exploit the full potential of motion capture with progress towards automatic recognition of gesture and, eventually, real-time systems. Automatic tracking and recognition systems are in high demand and the interlacing of data from multiple modes is now computationally achievable. SeeHear! will be coded using techniques in multimodal fusion - tracking of bodies will be enhanced by locating and recogn ....See Hear! Multimodal Recording and Analysis Facility. High resolution recording and analysis will exploit the full potential of motion capture with progress towards automatic recognition of gesture and, eventually, real-time systems. Automatic tracking and recognition systems are in high demand and the interlacing of data from multiple modes is now computationally achievable. SeeHear! will be coded using techniques in multimodal fusion - tracking of bodies will be enhanced by locating and recognizing facial features, and a learning algorithm used to classify gesture from patterns of force and physiological response. In the future, full interactivity will be achieved by interconnecting visual and auditory data with a flow on to applications in the performing arts, rehabilitation and security.Read moreRead less
Small States' use of law of the sea litigation against greater powers. This project will investigate how small States are using law of the sea dispute settlement mechanisms to gain political advantages in conflicts with greater powers, including Security Council permanent members. It is important to understand how the UN Convention on the Law of the Sea can be leveraged to defend coastal State rights in strategic disputes concerning sovereign rights, unresolved boundaries, and military affairs. ....Small States' use of law of the sea litigation against greater powers. This project will investigate how small States are using law of the sea dispute settlement mechanisms to gain political advantages in conflicts with greater powers, including Security Council permanent members. It is important to understand how the UN Convention on the Law of the Sea can be leveraged to defend coastal State rights in strategic disputes concerning sovereign rights, unresolved boundaries, and military affairs. This research will better equip lawyers and policy makers to understand how such strategic litigation strengthens or undermines the rules based order at sea. The project will assist Australia to maintain its leading role in defending that maritime order and the UN Convention on the Law of the Sea as its cornerstone.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100048
Funder
Australian Research Council
Funding Amount
$630,000.00
Summary
Atmospheric integrated research on burdens and oxidative capacity. Atmospheric integrated research on burdens and oxidative capacity: No single player in the Australian research community can make a large suite of atmospheric composition measurements, while the combined capability of the community is tremendous. Providing a platform to bring this capability together is cost effective and is expected to provide strong scientific return. This defines the requirements for Atmospheric Integrated Res ....Atmospheric integrated research on burdens and oxidative capacity. Atmospheric integrated research on burdens and oxidative capacity: No single player in the Australian research community can make a large suite of atmospheric composition measurements, while the combined capability of the community is tremendous. Providing a platform to bring this capability together is cost effective and is expected to provide strong scientific return. This defines the requirements for Atmospheric Integrated Research on Burdens and Oxidative capacity (AIR-BOX) to make a valuable contribution to Australian Atmospheric Science research. This project aims to provide a suite of mobile equipment including a chemical ionisation mass spectrometer, an ultraviolet-visible radiation spectrometer, a mini micropulse lidar, an in situ Fourier transform infrared spectrometer, and a cloud condensation nuclei counter. It will be capable of remote and autonomous deployment, real-time data transfer and control, a wide range of tracer measurements, flexible configuration, and physical as well as tracer measurements.Read moreRead less