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
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.
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
A multi-agent system for stakeholder management in off-site construction. This project aims to investigate a socio-technology model for stakeholders and informatics to improve off-site construction (OSC) productivity in infrastructure construction. A multi-agent system for OSC could drive down cost, but requires highly integrated collaboration among stakeholders. The project’s quantitative approaches include large-scale social network analysis, multi-agent consensus modelling and an optimisation ....A multi-agent system for stakeholder management in off-site construction. This project aims to investigate a socio-technology model for stakeholders and informatics to improve off-site construction (OSC) productivity in infrastructure construction. A multi-agent system for OSC could drive down cost, but requires highly integrated collaboration among stakeholders. The project’s quantitative approaches include large-scale social network analysis, multi-agent consensus modelling and an optimisation algorithm for collaborative planning. The project outcomes are expected to secure long-term economic benefits by enhancing performance in complex projects.Read moreRead less
Decoding the process of holistic shape encoding in the human visual system. The visual coding of shape is an important stage in object perception and yet we currently do not fully understand how shapes are encoded by the brain. This project aims to discover the cues used by the visual system to holistically represent shape and to explore the functional interactions between the cortical regions responsible for this task.
Judges' work, place and psychological health - a national view. This project aims to address the human, juridical and financial costs of judicial officers’ work-related psychological harm. This harm is implicated in early retirement, sick leave and suicide. It threatens appropriate courtroom conduct, procedural fairness and impartial adjudication. The project seeks to generate new knowledge of the stress judicial officers experience and the individual and institutional mechanisms for managing st ....Judges' work, place and psychological health - a national view. This project aims to address the human, juridical and financial costs of judicial officers’ work-related psychological harm. This harm is implicated in early retirement, sick leave and suicide. It threatens appropriate courtroom conduct, procedural fairness and impartial adjudication. The project seeks to generate new knowledge of the stress judicial officers experience and the individual and institutional mechanisms for managing stressors, combining socio-legal and psychological approaches. Expected outcomes include evidence-based understandings to inform recruitment and retention strategies specific to this highly specialized workforce. This should provide significant benefits for judges’ work capacities and courts' delivery of justice.Read moreRead less
Creating perceptual experts in Australia's policing and security agencies. This project aims to create the next generation of experts in Australia’s policing and national security agencies, by improving crime scene evidence interpretation. Agencies are under pressure to develop more rigorous training practices that go beyond mere intuition and tradition. This project will use a novel approach that directs learning toward the most diagnostic perceptual cues. Expected outcomes include a solid empi ....Creating perceptual experts in Australia's policing and security agencies. This project aims to create the next generation of experts in Australia’s policing and national security agencies, by improving crime scene evidence interpretation. Agencies are under pressure to develop more rigorous training practices that go beyond mere intuition and tradition. This project will use a novel approach that directs learning toward the most diagnostic perceptual cues. Expected outcomes include a solid empirical basis for national training programs designed to create experts that are accurate, reliable, and continuously improving. Improving the training of experts will ensure the integrity of forensics as evidentiary tools available to police, lead to more reliable courtroom convictions and help safeguard Australia from terrorism and crime.Read moreRead less
Effect of deep-sea drilling on sustainability of deep-sea ecosystems. Offshore oil and gas production makes a significant contribution to the Australian economy and enhances our energy security. Australia's vast deep-sea reserves of hydrocarbons lie on the NW Shelf and in Bass Strait, ecological 'hot spots' that are extremely vulnerable to the impact of exploration, extraction and production. Using deep-sea equipment, we will conduct the field experiments that are essential to understanding the ....Effect of deep-sea drilling on sustainability of deep-sea ecosystems. Offshore oil and gas production makes a significant contribution to the Australian economy and enhances our energy security. Australia's vast deep-sea reserves of hydrocarbons lie on the NW Shelf and in Bass Strait, ecological 'hot spots' that are extremely vulnerable to the impact of exploration, extraction and production. Using deep-sea equipment, we will conduct the field experiments that are essential to understanding these ecosystems and the impact of deep-sea structures. Our advances will produce data and develop methodologies that will make Australia a world leader in reconciling our deep-sea energy and environmental needs.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100019
Funder
Australian Research Council
Funding Amount
$664,580.00
Summary
Collaborative robotics for structural assembly and construction automation. Recent robotic technologies present great opportunity for construction industry to improve quality and productivity while no state of the art research infrastructure has been developed yet for this need. The proposed facility aims to provide a unique platform on research and development for structural assembly and construction automation. It
features by a flexible and adaptive design and instrumentation of structures and ....Collaborative robotics for structural assembly and construction automation. Recent robotic technologies present great opportunity for construction industry to improve quality and productivity while no state of the art research infrastructure has been developed yet for this need. The proposed facility aims to provide a unique platform on research and development for structural assembly and construction automation. It
features by a flexible and adaptive design and instrumentation of structures and space for a team of collaborative robotics in an interactive environment to achieve automated prefabrication, assembly and building. The outcomes are expected to transform current labor-intensive construction industry to highly automated and accurate manufacturing industry with significant benefits to economy and safety.Read moreRead less