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: DE170100102
Funder
Australian Research Council
Funding Amount
$304,080.00
Summary
Managing land surface radiation management to reduce the intensity of heat waves. This project aims to use land surface radiation management to reduce the intensity of heat waves. Heat waves have high social, environmental, and economic effects, and their intensity will increase. Using climate models, this project will examine how altering current land management practices could change properties of soils and vegetation to reduce the intensity of heat waves. The expected outcomes of this project ....Managing land surface radiation management to reduce the intensity of heat waves. This project aims to use land surface radiation management to reduce the intensity of heat waves. Heat waves have high social, environmental, and economic effects, and their intensity will increase. Using climate models, this project will examine how altering current land management practices could change properties of soils and vegetation to reduce the intensity of heat waves. The expected outcomes of this project are information on adaptation to the increasing intensity of heat waves in Australia, which will be applicable globally.Read moreRead less
Leveraging research and development (R and D) for the Australian built environment. This project will evaluate impacts, diffusion mechanisms and uptake of research and development (R and D) in the Australian building and construction industry. Building on a retrospective analysis and industry consultation, a future-focussed industry roadmap will be developed to establish R and D policies to inform and improve R and D investment effectiveness.
Measuring and modelling the mechanical response of soils incorporating recycled tyres. Civil engineers use backfill to refill excavated areas around new structures. They have found recently that rubber chips and shredded rubber make excellent backfill when combined with a small percentage of cement to make ‘rubber soil’. The widespread use of rubber soil therefore offers a tremendous opportunity to make use of a serious waste product to achieve important engineering outcomes. However, too little ....Measuring and modelling the mechanical response of soils incorporating recycled tyres. Civil engineers use backfill to refill excavated areas around new structures. They have found recently that rubber chips and shredded rubber make excellent backfill when combined with a small percentage of cement to make ‘rubber soil’. The widespread use of rubber soil therefore offers a tremendous opportunity to make use of a serious waste product to achieve important engineering outcomes. However, too little is known about the technology. This project will model the behaviour of rubber soil in order to introduce it as an environmentally sustainable, cost-effective and technically sound choice of geomaterial for both standard and non-standard geotechnical structures.Read moreRead less
Neural metrics for space time and numerosity. What we propose is ground-breaking research. It will increase Australia's international competitiveness is science, expand the knowledge base of brain function and psychology and provide valuable training for research scientists.
Design and Construction Error Mitigation in Infrastructure Projects. Human errors committed during the design and construction process of infrastructure projects increase costs by as much as 25 per cent. The costs associated with such errors would be significantly higher in the event of an engineering failure and loss of life. This research will develop a model that can be used to mitigate errors and improve the performance and safety of infrastructure projects. A reduction in errors will reduce ....Design and Construction Error Mitigation in Infrastructure Projects. Human errors committed during the design and construction process of infrastructure projects increase costs by as much as 25 per cent. The costs associated with such errors would be significantly higher in the event of an engineering failure and loss of life. This research will develop a model that can be used to mitigate errors and improve the performance and safety of infrastructure projects. A reduction in errors will reduce the financial burden placed on taxpayers for cost overruns experienced as well as improve the profitability of organisations. This will lead to greater investment, and contribution to gross domestic product.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100101
Funder
Australian Research Council
Funding Amount
$744,697.00
Summary
New generation facility for impact testing. This project aims to develop a new generation, national-impact testing facility to study the impact response of civil and mechanical structures and components. This project expects to seek simultaneous, realistic impact scenarios with very high velocities, which were previously impossible. This will enhance the capability for innovative research on real-time behaviour of components/systems under high amplitude impacts to augment their protection throug ....New generation facility for impact testing. This project aims to develop a new generation, national-impact testing facility to study the impact response of civil and mechanical structures and components. This project expects to seek simultaneous, realistic impact scenarios with very high velocities, which were previously impossible. This will enhance the capability for innovative research on real-time behaviour of components/systems under high amplitude impacts to augment their protection through advanced materials. This project is essential for research on rational design philosophies and effective retrofitting of high-risk buildings, infrastructure and armoured vehicles. Benefits include the saving of lives and property through new knowledge from credible impact testing.Read moreRead less
Characterising and linking intermediate-level processing of pattern, motion and position in human vision? This work will advance basic science by enhancing understanding of human coding of image structure. The aim is to provide a common structure for understanding visual processing of form, motion and position. The work will help lift the international profile of Australian science. Explaining how the primitives for shape perception are extracted will also have consequences of potential economic ....Characterising and linking intermediate-level processing of pattern, motion and position in human vision? This work will advance basic science by enhancing understanding of human coding of image structure. The aim is to provide a common structure for understanding visual processing of form, motion and position. The work will help lift the international profile of Australian science. Explaining how the primitives for shape perception are extracted will also have consequences of potential economic benefit. One important aspect is the design of displays that allow observers to absorb complex information about rapidly changing situations. This work has the potential to provide information that enables display designers to optimise the efficiency of presentation of pattern and motion information.Read moreRead less
How the human visual system uses pattern information to organize motion. This project is an investigation into human vision, a priority area for ARC. Its aim is to discover how photons from moving objects leave traces in the human visual system that assist it to determine the path of local motion and the structure of global motion. Its theoretical significance is that it will lead to substantial revisions of current models of human visual processing. Its practical significance is that it will pr ....How the human visual system uses pattern information to organize motion. This project is an investigation into human vision, a priority area for ARC. Its aim is to discover how photons from moving objects leave traces in the human visual system that assist it to determine the path of local motion and the structure of global motion. Its theoretical significance is that it will lead to substantial revisions of current models of human visual processing. Its practical significance is that it will provide a theoretical basis for the design of display systems that are more effective in conveying information about motion to human observers and eliminate errors inherent in existing systems.Read moreRead less