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
Discovery Early Career Researcher Award - Grant ID: DE120102645
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The cause of the poleward shift of Earth's storm tracks and jet streams. Why do global climate models shift the atmospheric storm tracks and jet streams poleward in simulations of future climate? This project will determine the underlying causes of the most important circulation change that is projected to occur with increasing greenhouse gases, and will allow much more accurate regional climate projections.
Transforming our research capacity in the analysis of climate extremes. Given their devastating impacts, there is now a critical urgency to understand what drives extreme climate events and make timely predictions of their future risk. The analysis of comprehensive extremes datasets, comprising global observations and output of multi-model simulations, will greatly improve our ability to answer fundamental questions about the nature and variability of extreme climatic events. This project also e ....Transforming our research capacity in the analysis of climate extremes. Given their devastating impacts, there is now a critical urgency to understand what drives extreme climate events and make timely predictions of their future risk. The analysis of comprehensive extremes datasets, comprising global observations and output of multi-model simulations, will greatly improve our ability to answer fundamental questions about the nature and variability of extreme climatic events. This project also ensures the government's continued commitment to managing the risks associated with extreme events as an urgent national priority. It represents a landmark opportunity for Australian leadership of an international collaboration between some of the world's leading climate scientists and climate data and modelling centres.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL150100035
Funder
Australian Research Council
Funding Amount
$2,765,281.00
Summary
Revisiting the physics of clouds. Revisiting the physics of clouds: This fellowship project aims to bring new rigour to climate modelling by improving our understanding of key phenomena like clouds and storms. Earth’s climate has taken a number of turns in the recent and geologic past that so far cannot be reproduced in models. Clouds and atmospheric turbulence are also a problem for weather and climate prediction, the conceptual understanding of which now has evident flaws. The hypothesis of th ....Revisiting the physics of clouds. Revisiting the physics of clouds: This fellowship project aims to bring new rigour to climate modelling by improving our understanding of key phenomena like clouds and storms. Earth’s climate has taken a number of turns in the recent and geologic past that so far cannot be reproduced in models. Clouds and atmospheric turbulence are also a problem for weather and climate prediction, the conceptual understanding of which now has evident flaws. The hypothesis of this project is that these two problems are strongly linked, and that this link may be exploited to solve problems across disciplines. This project aims to systematically re-evaluate our conceptual understanding of cloud physics, and investigate how this affects our understanding of climate phenomena in Earth’s past and future.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160101127
Funder
Australian Research Council
Funding Amount
$292,251.00
Summary
Cutting red tape around donations: A new model for deductible gifts. This project intends to simplify the categorisation of recipients of tax deductible gifts so that it is easy to give and receive gifts and so gifts go only to those organisations that are in keeping with public policy. Donations cost approximately $1.3 billion annually. It is therefore important that donation is a streamlined process that encourages social pluralism while ensuring there is a good use of public money. Research i ....Cutting red tape around donations: A new model for deductible gifts. This project intends to simplify the categorisation of recipients of tax deductible gifts so that it is easy to give and receive gifts and so gifts go only to those organisations that are in keeping with public policy. Donations cost approximately $1.3 billion annually. It is therefore important that donation is a streamlined process that encourages social pluralism while ensuring there is a good use of public money. Research indicates that the current approach to determining donation deductibility status is complex and out of step with government policy, public discourse and community needs. The proposed framework will be simple, take into account public policy and be adaptable to the community’s changing needs and values.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: DE170101191
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
The future intensity of extreme East Coast Lows. This project aims to determine the environmental factors controlling the intensity of extreme East Coast Lows and how their intensity responds to global warming conditions. East Coast Lows are responsible for much of the high-impact weather affecting the east coast of Australia. Understanding the causes behind future climate changes is critical to provide confidence in future projections. This project will use high-resolution climate models that c ....The future intensity of extreme East Coast Lows. This project aims to determine the environmental factors controlling the intensity of extreme East Coast Lows and how their intensity responds to global warming conditions. East Coast Lows are responsible for much of the high-impact weather affecting the east coast of Australia. Understanding the causes behind future climate changes is critical to provide confidence in future projections. This project will use high-resolution climate models that can realistically simulate all the key dynamic processes including atmosphere-ocean interactions. Expected outcomes are adaptation strategies to mitigate the future effect of East Coast Lows on coastal fresh water resources, flooding and erosion.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
Discovery Early Career Researcher Award - Grant ID: DE150100456
Funder
Australian Research Council
Funding Amount
$367,536.00
Summary
How far in advance can we predict extreme temperature and rainfall events? The occurrence of extreme temperature and precipitation events undergoes substantial seasonal to decadal variability, but little is known about their predictability. This project aims to examine variability and predictability of these climatic extremes and associated mechanisms. It will be the first to systematically investigate sources of predictability by incorporating the most comprehensive novel databases of both mult ....How far in advance can we predict extreme temperature and rainfall events? The occurrence of extreme temperature and precipitation events undergoes substantial seasonal to decadal variability, but little is known about their predictability. This project aims to examine variability and predictability of these climatic extremes and associated mechanisms. It will be the first to systematically investigate sources of predictability by incorporating the most comprehensive novel databases of both multi-model decadal climate simulations and observed climate extremes. This study is significant as it will lead to a vastly improved understanding of variability and predictability of climate extremes. This will enable improved climate predictions on seasonal to decadal timescales and ultimately improve longer-term projections.Read moreRead less