This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
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
Cloudiness over the Southern Ocean: reducing a key knowledge gap and source of climate model uncertainty. Southern Ocean clouds are key ingredients of the global climate system and yet are only poorly understood and poorly represented in climate models. Through the use of advanced observational analysis techniques this research will provide a deep understanding of key Southern Ocean cloud regimes and improve their representation in models.
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
'The fingers of the powers above do tune the harmony of this peace': Australia and the Harmonisation of Patents. Patent law is central to the key economic aim of encouraging an innovative culture. The harmonisation of patent systems around the world means Australian law will change. There is a significant risk that, without effective lobbying, the reforms will only reflect the needs and interests of the dominant economies, like the US. This project, with its comparative analysis of the patent e ....'The fingers of the powers above do tune the harmony of this peace': Australia and the Harmonisation of Patents. Patent law is central to the key economic aim of encouraging an innovative culture. The harmonisation of patent systems around the world means Australian law will change. There is a significant risk that, without effective lobbying, the reforms will only reflect the needs and interests of the dominant economies, like the US. This project, with its comparative analysis of the patent examination process, will explore the ways in which this integral part of the patent system may be improved. This research will lead to proposals for reform that are in line with the interests of Australia's unique economy.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
Towards a climate theory of tropical cyclone formation. In Earth's current climate, about 80 to 90 tropical cyclones form every year around the globe, but the reasons why cyclones form at this rate are unknown. This project will use a combination of theoretical techniques and numerical simulation to elucidate the links between large-scale climate and the rate of tropical cyclone formation. A series of climate model experiments will be performed that also have the potential to improve confidence ....Towards a climate theory of tropical cyclone formation. In Earth's current climate, about 80 to 90 tropical cyclones form every year around the globe, but the reasons why cyclones form at this rate are unknown. This project will use a combination of theoretical techniques and numerical simulation to elucidate the links between large-scale climate and the rate of tropical cyclone formation. A series of climate model experiments will be performed that also have the potential to improve confidence in our predictions of tropical cyclone incidence in a future, changed climate.Read moreRead less
The Southern Ocean boundary layer: winds, turbulence, sea spray and clouds. Both satellite products and climate models have large biases in the energy and water budgets over the Southern Ocean (SO). This is a direct consequence of a poor understanding of the structure and dynamics of the SO atmospheric boundary layer, which has arisen from an inability to make the necessary observations in this harsh environment. Due to the availability of new Australian research infrastructure, large steps forw ....The Southern Ocean boundary layer: winds, turbulence, sea spray and clouds. Both satellite products and climate models have large biases in the energy and water budgets over the Southern Ocean (SO). This is a direct consequence of a poor understanding of the structure and dynamics of the SO atmospheric boundary layer, which has arisen from an inability to make the necessary observations in this harsh environment. Due to the availability of new Australian research infrastructure, large steps forward are now possible with modest investment. This project will conduct and combine observations from the recently acquired marine vessel, RV Investigator, and the collocated airborne and surface observations to understand the structure and evolution of the unique, pristine SO boundary layer and to evaluate satellites and climate models.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