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
ARC Financial Integrity Research Network. The integrity of the financial system is constantly under stress because of the development of ever more complex financial instruments, structures and strategies, and the associated research technologies that continues to accelerate worldwide. FIRN's vision is to harness the considerable strengths of Australia's internationally renowned finance, accounting and economics researchers into a research agenda to address issues concerning the integrity of the ....ARC Financial Integrity Research Network. The integrity of the financial system is constantly under stress because of the development of ever more complex financial instruments, structures and strategies, and the associated research technologies that continues to accelerate worldwide. FIRN's vision is to harness the considerable strengths of Australia's internationally renowned finance, accounting and economics researchers into a research agenda to address issues concerning the integrity of the financial system. It will enable Australian research in this area to match the scale and impact of similar research in other major international financial centres, and play an essential role in placing Australia among the world's leaders in financial markets related research.Read moreRead less
Infill Developments: Project HOME (Housing Outcomes Metrics and Evaluation). The project plans to improve housing outcomes by evaluating housing design in the rapidly growing infill multi-residential sector, which often experiences design quality problems. Set across four global cities, the project aims to use a unique combination of design and social science methods to analyse good design and how this is produced and experienced. It is expected that this will deliver greater definition of and e ....Infill Developments: Project HOME (Housing Outcomes Metrics and Evaluation). The project plans to improve housing outcomes by evaluating housing design in the rapidly growing infill multi-residential sector, which often experiences design quality problems. Set across four global cities, the project aims to use a unique combination of design and social science methods to analyse good design and how this is produced and experienced. It is expected that this will deliver greater definition of and evidence for ‘good’ design as experienced through the real lives of Australian households. Outcomes should include robust design evaluation methods and transition strategies for cities, allowing city decision-makers to improve housing design for many people in Australian cities.Read moreRead less
Stochastic Analysis with a View to Applications in Financial Risk Processes. Recent decades have seen explosive growth in applications of probability theory and statistics to the modelling of risk in finance and insurance. An intensive theoretical investigation into passage time and other problems for Levy and other continuous time processes will be applied to financial risk analyses. Related investigations will involve perpetuities and stochastic volatility models for price series. Outcomes ....Stochastic Analysis with a View to Applications in Financial Risk Processes. Recent decades have seen explosive growth in applications of probability theory and statistics to the modelling of risk in finance and insurance. An intensive theoretical investigation into passage time and other problems for Levy and other continuous time processes will be applied to financial risk analyses. Related investigations will involve perpetuities and stochastic volatility models for price series. Outcomes will include the development of new theory in probability and statistics, the initiation and reinforcement of collaborative ties with major international research figures, and the fostering of contacts with the finance industry.Read moreRead less
Industrial Transformation Research Hubs - Grant ID: IH130200012
Funder
Australian Research Council
Funding Amount
$2,748,358.00
Summary
ARC Research Hub for Basin GEodyNamics and Evolution of SedImentary Systems (GENESIS). ARC Research Hub for Basin GEodyNamics and Evolution of SedImentary Systems (GENESIS). This Research Hub aims to undertake simultaneous modelling of deep Earth and surface processes, spanning basin scales to individual sediment grains. The Hub will develop and apply cutting-edge basin simulation approaches to transform the seeding and testing of basin exploration models, extending their viability to complex, ....ARC Research Hub for Basin GEodyNamics and Evolution of SedImentary Systems (GENESIS). ARC Research Hub for Basin GEodyNamics and Evolution of SedImentary Systems (GENESIS). This Research Hub aims to undertake simultaneous modelling of deep Earth and surface processes, spanning basin scales to individual sediment grains. The Hub will develop and apply cutting-edge basin simulation approaches to transform the seeding and testing of basin exploration models, extending their viability to complex, inaccessible remote and deep exploration targets. The Hub will fuse multidimensional data into five dimensional basin models (space and time, with uncertainty estimates) by coupling the evolution of mantle flow, crustal deformation, erosion and sedimentary processes, achieving a quantum leap in basin modelling and petroleum systems analysis.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100174
Funder
Australian Research Council
Funding Amount
$805,000.00
Summary
Urban Analytics Data Infrastructure. Urban analytics data infrastructure:
This project aims to develop an urban analytics data infrastructure that builds on the Australian Urban Research Infrastructure Network. This digital data infrastructure intends to enable the integration, harmonisation, connectivity and scalability of multi-source urban datasets. This infrastructure is required to underpin the next generation of data-driven modelling and decision-support tools to enable the design of smar ....Urban Analytics Data Infrastructure. Urban analytics data infrastructure:
This project aims to develop an urban analytics data infrastructure that builds on the Australian Urban Research Infrastructure Network. This digital data infrastructure intends to enable the integration, harmonisation, connectivity and scalability of multi-source urban datasets. This infrastructure is required to underpin the next generation of data-driven modelling and decision-support tools to enable the design of smart, productive and resilient cities. These capabilities are predicated on the adoption of ISO standards, development of new ontological frameworks and an urban data dictionary to enable semantic inferencing of datasets and the development of data structures and services. This framework would then be applied to data relevant to people, land and urban infrastructure to support comparative and multi-dimensional analytics. Read moreRead less
Evolution of Proterozoic multistage rift basins – key to mineral systems. This project will deliver a new quantitative and integrated exploratory framework for the mineral industry in Australia’s frontier sedimentary basins by integrating the latest advances in laboratory experimental tectonics with thermo-mechanical numerical, surface process and geophysical modelling. The project will use northern Australian basins as a natural laboratory to address the fundamental processes involved in the de ....Evolution of Proterozoic multistage rift basins – key to mineral systems. This project will deliver a new quantitative and integrated exploratory framework for the mineral industry in Australia’s frontier sedimentary basins by integrating the latest advances in laboratory experimental tectonics with thermo-mechanical numerical, surface process and geophysical modelling. The project will use northern Australian basins as a natural laboratory to address the fundamental processes involved in the development of sedimentary ore systems. The project will investigate how they can be detected by modern exploration techniques using a multidisciplinary approach with a team of experts with backgrounds in mineral and petroleum systems. Read moreRead less
Protecting while they prosper? Organisational responses to whistleblowing. This project aims to examine the adequacy of organisational responses to whistleblowing (employee reporting of wrongdoing). So far, research into public-interest whistleblowing has revealed much about the incidence, significance and experience of whistleblowers. This project now extends the research to the other side of the issue — the organisations. By comparing employee and managerial experience in multiple public and p ....Protecting while they prosper? Organisational responses to whistleblowing. This project aims to examine the adequacy of organisational responses to whistleblowing (employee reporting of wrongdoing). So far, research into public-interest whistleblowing has revealed much about the incidence, significance and experience of whistleblowers. This project now extends the research to the other side of the issue — the organisations. By comparing employee and managerial experience in multiple public and private sector organisations in Australia and New Zealand, the project intends to identify the factors that influence good and bad responses across a range of institutions; provide a clearer basis for reform of policies, procedures and law; and set benchmarks for comparative research worldwide.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100043
Funder
Australian Research Council
Funding Amount
$539,000.00
Summary
The Australian Royal Commissions and Public Inquiries Library. This project aims to provide comprehensive free access online to the reports of all royal commissions and other public inquiries held in Australia since Federation. The project
intends to support a wide understanding of the pivotal role public inquiries play in the development of Australian law and public policy. It is expected that these reports will be comprehensively integrated with all other legislation, case law and law reform r ....The Australian Royal Commissions and Public Inquiries Library. This project aims to provide comprehensive free access online to the reports of all royal commissions and other public inquiries held in Australia since Federation. The project
intends to support a wide understanding of the pivotal role public inquiries play in the development of Australian law and public policy. It is expected that these reports will be comprehensively integrated with all other legislation, case law and law reform reports on AustLII to promote a greater understanding of how the balance is struck between inquisitorial fact-finding and the right to procedural fairness of participants and of how justice is delivered through the inquiry function of public bodies.Read moreRead less