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
Governance of information technology programmes: achieving accountability, control and success. This project aims to improve the effectiveness with which IT-enabled programmes are managed by public and private organisations. The theoretical knowledge and guides for good practice emerging from this study will contribute to increased success in managing and delivering complex and vital programmes across Australia.
Discovery Early Career Researcher Award - Grant ID: DE130100860
Funder
Australian Research Council
Funding Amount
$365,586.00
Summary
Upgrading competitive position through foreign direct investment: understanding the role of managerial intentionality in domestic manufacturing firms. This research investigates the process by which firms from small domestic markets, such as Australia, can catch up with global market leaders through acquiring strategic assets overseas. It aims to reveal the role of the strategic intents of firm decision makers in initiating, strategising and supporting the process of competitive catch-up.
Integrating Economic Valuation and Water Quality Modelling for Improving Management of Coastal Catchments. This project will apply and integrate water quality models and economic assessment techniques to assist policy makers and catchment managers balance competing development pressures and environmental concerns in coastal catchments. The research is fundamental to underpinning the sustainable management of coastal catchments which provide major economic, environmental and community benefits. T ....Integrating Economic Valuation and Water Quality Modelling for Improving Management of Coastal Catchments. This project will apply and integrate water quality models and economic assessment techniques to assist policy makers and catchment managers balance competing development pressures and environmental concerns in coastal catchments. The research is fundamental to underpinning the sustainable management of coastal catchments which provide major economic, environmental and community benefits. The project will provide robust tools to predict water quality impacts under a range of conditions and it will develop techniques for the economic valuation of market and non-market impacts. The project will demonstrate the integration of water quality and economic modelling and how it can influence policy and investment in conservation and remediation.Read moreRead less
Cover crops that decrease phosphorus (P) transport from agricultural soils by increasing the efficiency of P fertiliser application. The aim of this project is to develop cover crop practices for the heavily fertilised potato cropping soils of the Robertson district that will minimise erosion and runoff of water potentially rich in phosphorus (P), thereby resulting in significant improvements in the environmental management of this sensitive catchment area. The cover crops will: (i) improve infi ....Cover crops that decrease phosphorus (P) transport from agricultural soils by increasing the efficiency of P fertiliser application. The aim of this project is to develop cover crop practices for the heavily fertilised potato cropping soils of the Robertson district that will minimise erosion and runoff of water potentially rich in phosphorus (P), thereby resulting in significant improvements in the environmental management of this sensitive catchment area. The cover crops will: (i) improve infiltration, decrease erosion, and off-site transport of P; (ii)increase access to accumulated soil P, making it available to a subsequent potato crop, thus decreasing the P loading of the soil; and (iii) have a biofumigation effect that will reduce the use of soil fumigants.
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Industrial Transformation Training Centres - Grant ID: IC190100033
Funder
Australian Research Council
Funding Amount
$3,852,568.00
Summary
ARC Training Centre for Transformation of Australia's Biosolids Resource. This Centre aims to bring together Australia’s leading biosolids researchers and key industry and government stakeholders to advance the management, transformation and reuse of biosolids in agriculture. The focus is: 1) capability and knowledge building, 2) research development, extension and training, 3) sustainable strategic partnerships. The expected outcomes of the Centre are to develop a group of new, highly-trained i ....ARC Training Centre for Transformation of Australia's Biosolids Resource. This Centre aims to bring together Australia’s leading biosolids researchers and key industry and government stakeholders to advance the management, transformation and reuse of biosolids in agriculture. The focus is: 1) capability and knowledge building, 2) research development, extension and training, 3) sustainable strategic partnerships. The expected outcomes of the Centre are to develop a group of new, highly-trained industry-ready researchers as well as advanced solutions in three major themes: improved technologies, enhanced products and sustainability. This will provide significant benefits in the economic value of new applications and market opportunities as well as deliver cost-savings – all in an environmentally friendly manner.Read moreRead less
Multi-level analysis of human resource management systems on hospital outcomes. This project explores the relationships among human resource management systems, perceived organisational support, trust-in-management and commitment of healthcare workers. The fundamental aim is to assist hospital managers to determine where to direct their efforts to have maximum impact upon staff and hospital performance.
Water, carbon, and economics: resolving complex linkages for river health. By linking landscapes into our emerging low-carbon economy, this project will investigate how land management practices can be improved through payments for ecosystem services. With a focus on water and carbon, the main goal is to develop mechanisms to support integrated land and water management at the catchment scale.
Industrial Transformation Training Centres - Grant ID: IC190100031
Funder
Australian Research Council
Funding Amount
$3,973,202.00
Summary
ARC Training Centre in Data Analytics for Resources and Environments (DARE). Understanding the cumulative impact of actions regarding the use of our resources has important long-term consequences for Australia’s economic, societal and environmental health. Yet despite the importance of these cumulative impacts, and the availability of data, many decisions and policies are based on limited amounts of data and rudimentary data analysis, with little appreciation of the critical role that understand ....ARC Training Centre in Data Analytics for Resources and Environments (DARE). Understanding the cumulative impact of actions regarding the use of our resources has important long-term consequences for Australia’s economic, societal and environmental health. Yet despite the importance of these cumulative impacts, and the availability of data, many decisions and policies are based on limited amounts of data and rudimentary data analysis, with little appreciation of the critical role that understanding and quantifying uncertainty plays in the process. The aim of Data Analytics in Resources and Environment (DARE) is to develop and deliver the data science skills and tools for Australia’s resource industries to make the best possible evidence-based decisions in exploiting and stewarding the nation’s natural resources.Read moreRead less