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
Cloud-climate interaction over the Great Barrier Reef and Southwest Pacific. This project aims to investigate cloud-climate interactions of the Southwest Pacific trade wind region from the regional scale to local forcing over the Great Barrier Reef. The project expects to generate new knowledge in the nature and variability of the trade wind clouds, including their impact on the surface radiative budget, ocean temperatures and coral bleaching events. Potential changes of these clouds due to glob ....Cloud-climate interaction over the Great Barrier Reef and Southwest Pacific. This project aims to investigate cloud-climate interactions of the Southwest Pacific trade wind region from the regional scale to local forcing over the Great Barrier Reef. The project expects to generate new knowledge in the nature and variability of the trade wind clouds, including their impact on the surface radiative budget, ocean temperatures and coral bleaching events. Potential changes of these clouds due to global warming and ensuing impacts on the environment will be studied. Expected outcomes include better modelling of the Great Barrier Reef environment and improved estimates of low-cloud feedback. This should provide significant benefits in developing warning systems for bleaching events, and regional land and water management. Read moreRead less
Do regional climate models rain too much? This project aims to provide a best-practice, in-depth assessment of the climate model simulations that are used to support regional climate change impact assessments. The focus will be on rainfall and the hydrological cycle as these aspects are especially impacts-relevant. Innovation comes from the application of a common benchmarking framework which includes observational uncertainty and process-based understanding to address common modelling limitatio ....Do regional climate models rain too much? This project aims to provide a best-practice, in-depth assessment of the climate model simulations that are used to support regional climate change impact assessments. The focus will be on rainfall and the hydrological cycle as these aspects are especially impacts-relevant. Innovation comes from the application of a common benchmarking framework which includes observational uncertainty and process-based understanding to address common modelling limitations. Any model failings identified will feed into model development strategies and support enhanced decision-making informed by regional climate model simulations.Read moreRead less
Local climate changes caused by large bushfire burnt areas. This project aims to quantify the impact on local climate produced by large burnt areas after extreme bushfires. This project expects to generate new knowledge on these previously unexplored fire-scar induced changes to local climate. It will extend an innovative approach that combines satellite based earth observation with very high resolution regional climate modelling to quantify the impacts on land-atmosphere feedbacks and local cli ....Local climate changes caused by large bushfire burnt areas. This project aims to quantify the impact on local climate produced by large burnt areas after extreme bushfires. This project expects to generate new knowledge on these previously unexplored fire-scar induced changes to local climate. It will extend an innovative approach that combines satellite based earth observation with very high resolution regional climate modelling to quantify the impacts on land-atmosphere feedbacks and local climate. Expected outcomes of this project include enhanced methods to quantify local climate changes after extreme fires and their effect on vegetation recovery. This should provide significant benefits to the planning for, and management of, vegetation recovery after extreme fires.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