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
$285,990.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin i ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin is down-regulated by either erythroid differentiation or the haem precursor protoporphyrin IX (Becker and Richardson, submitted). These data strongly suggest a role for frataxin in iron metabolism. In the present study we will continue to assess if frataxin plays a role in the way cells handle iron. Using a unique model of mitochondrial iron overload developed in my lab (Richardson et al. (1996) BLOOD 87:3477), we will extensively investigate the iron metabolism of the mitochondrion in order to determine the function of frataxin and its role in Friedreich's ataxia. In addition, we have developed a series of new drugs known as iron chelators that can enter the mitochondrion due to their high lipid solubility (Becker and Richardson 1999 J. Lab. Clin. Med. 134:510). These latter drugs are far more effective than the chelator currently used to treat iron overload, desferrioxamine (DFO). Indeed, our chelators have been designed to result in high iron chelation efficacy but low toxicity (see Becker and Richardson, 1999). This exciting research may be crucial in understanding the development of FA and in creating new therapies such as the use of iron chelators.Read moreRead less
HISTORICAL EXPERTS AND INDIGENOUS LITIGANTS: the role of Historical Expert Evidence in Federal Court Cases. Since Mabo, historians are increasingly being called as expert witnesses in cases involving indigenous litigants. Historians perceive serious difficulties in the Court's treatment of qualitative, historical material, resulting in a possible denial of access to justice. The project investigates this treatment, pursuing issues such as expert evidence generally, the specific relationship betw ....HISTORICAL EXPERTS AND INDIGENOUS LITIGANTS: the role of Historical Expert Evidence in Federal Court Cases. Since Mabo, historians are increasingly being called as expert witnesses in cases involving indigenous litigants. Historians perceive serious difficulties in the Court's treatment of qualitative, historical material, resulting in a possible denial of access to justice. The project investigates this treatment, pursuing issues such as expert evidence generally, the specific relationship between Law and History, and the particularity of cases involving indigenous claims. The investigation asks whether historians as expert witnesses can retain both their historical professionalism and adapt to the requirements of the courts, or whether the courts? rules of evidence themselves require adaptation.
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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454207
Funder
Australian Research Council
Funding Amount
$311,381.00
Summary
New Technology to Fight Crime and Terrorism: Laser Ablation Inductively Coupled Plasma Mass Spectrometer Facilities (LA-ICP-MS). Australia urgently needs new technologies to prevent and fight crime and terrorism. This equipment will address current outstanding problems in forensic science and related disciplines, namely the requirement to (1) analyse minute quantities of samples, (2) differentiate samples with similar matrices but trace differences, (3) analyse solid samples that are difficult t ....New Technology to Fight Crime and Terrorism: Laser Ablation Inductively Coupled Plasma Mass Spectrometer Facilities (LA-ICP-MS). Australia urgently needs new technologies to prevent and fight crime and terrorism. This equipment will address current outstanding problems in forensic science and related disciplines, namely the requirement to (1) analyse minute quantities of samples, (2) differentiate samples with similar matrices but trace differences, (3) analyse solid samples that are difficult to analyse by current techniques. This equipment is also vital for research which will improve the justice system, the quality of food and health products and increase industry competitiveness through novel industrial and environmental testing. Acquiring this infrastructure will safeguard and ensure Australia's continuing prosperity.Read moreRead less
Detecting Fraud and Anti-Competitive Behaviour in the Australian Pharmaceutical and Medical Device Industries. This Project will deliver law reform proposals to ensure greater accountability and a reduction of fraud and anti-competitive behaviour associated with over 6 billion dollars of public money expended each year under the Pharmaceutical Benefits Scheme (PBS) as well as significant amounts paid by public hospitals on medical devices. It unites experts in Australian pharmaceutical regulatio ....Detecting Fraud and Anti-Competitive Behaviour in the Australian Pharmaceutical and Medical Device Industries. This Project will deliver law reform proposals to ensure greater accountability and a reduction of fraud and anti-competitive behaviour associated with over 6 billion dollars of public money expended each year under the Pharmaceutical Benefits Scheme (PBS) as well as significant amounts paid by public hospitals on medical devices. It unites experts in Australian pharmaceutical regulation and high technology law enforcement with an eminent United States Partner Investigator in False Claims litigation. Reducing fraud and anti-competitive behaviour could be critical to survivability of the PBS and the benefits it brings particularly to an ageing population. Read moreRead less
Juries and interactive visual evidence: impacts on deliberation processes and outcomes. Australia confronts new types of security threat in the form of terrorist networks, sophisticated money-laundering and people-smuggling operations. The AFP and prosecutors are developing new display technologies to explain complex information to jurors, in the process simplifying court processes and shortening trials. At the cutting edge of this development are interactive displays, including computer simulat ....Juries and interactive visual evidence: impacts on deliberation processes and outcomes. Australia confronts new types of security threat in the form of terrorist networks, sophisticated money-laundering and people-smuggling operations. The AFP and prosecutors are developing new display technologies to explain complex information to jurors, in the process simplifying court processes and shortening trials. At the cutting edge of this development are interactive displays, including computer simulations and 360o crime scene reconstructions. Judges will use empirical information about how juries use such information in order to develop appropriate guidelines for admitting interactive visual evidence, while court planners and architects will use the project data to identify implications for court procedures and design.
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A Comparative Law and Economics Analysis of Class Actions in Australia, the US and the UK. Research on how class action law suits operate to enforce rules and rights in the civil justice system, can promote three of the four national research priorities. By enabling better enforcement of competition, contract and corporations law for consumers and investors encourages better performing markets, corporations, and in turn an innovation culture and economy. By enabling better enforcement of produ ....A Comparative Law and Economics Analysis of Class Actions in Australia, the US and the UK. Research on how class action law suits operate to enforce rules and rights in the civil justice system, can promote three of the four national research priorities. By enabling better enforcement of competition, contract and corporations law for consumers and investors encourages better performing markets, corporations, and in turn an innovation culture and economy. By enabling better enforcement of product safety laws (e.g. asbestos and tobacco) it will promote better products and services and thus better health of users over time. Finally by enabling better enforcement of environmental law it will help address the water crisis and climate change.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775482
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
Ultratrace element and isotope analysis facility. Analysis of trace concentrations of contaminants in food, water and biota is essential for proper environmental and human health protection, and the ability to analyse different isotopes of nutrients will improve our capability to develop techniques to fortify foods with essential micronutrients. The instrumentation will also assist our understanding of the geological processes, climate and environmental change and the formation and location of m ....Ultratrace element and isotope analysis facility. Analysis of trace concentrations of contaminants in food, water and biota is essential for proper environmental and human health protection, and the ability to analyse different isotopes of nutrients will improve our capability to develop techniques to fortify foods with essential micronutrients. The instrumentation will also assist our understanding of the geological processes, climate and environmental change and the formation and location of mineral deposits having economic potential in Australia. By improving forensic identification techniques, the instrumentation will allow identification and tracking of environmental contamination of the food chain and water supplies, and to identify and track criminal and terrorist activity. Read moreRead less
Beyond Scenarios: Testable Models of the Evolution of Norms. The aim of this project is to investigate the evolution of social norms, and their causal role in social life and its breakdown. It expects to generate new knowledge in this area through the application of new formal techniques to existing hypotheses; especially causal analysis, evolutionary game theory, and phylogenetic cross-cultural testing for empirically plausibility. Expected outcomes include theory development, improved research ....Beyond Scenarios: Testable Models of the Evolution of Norms. The aim of this project is to investigate the evolution of social norms, and their causal role in social life and its breakdown. It expects to generate new knowledge in this area through the application of new formal techniques to existing hypotheses; especially causal analysis, evolutionary game theory, and phylogenetic cross-cultural testing for empirically plausibility. Expected outcomes include theory development, improved research infrastructure and training in collaboration with international partners, and theoretical recommendations for policy intervention. This should allow greater insight and control over the levers of peaceful social life, both in traditional societies, and in large, open, multi-cultural nations like Australia. Read moreRead less
The Indian Roots of Modern Chinese Thought. The Project will strengthen Australia's capacity to interpret and engage with our regional and global environments by demonstrating the need for greater understanding of the nationalistic appeal that Yogâcâra thought has held for Chinese intellectuals; and the rise of New Confucianism as a philosophical movement associated with robust expressions of cultural nationalism. It will also further enhance Australia's international intellectual profile by bri ....The Indian Roots of Modern Chinese Thought. The Project will strengthen Australia's capacity to interpret and engage with our regional and global environments by demonstrating the need for greater understanding of the nationalistic appeal that Yogâcâra thought has held for Chinese intellectuals; and the rise of New Confucianism as a philosophical movement associated with robust expressions of cultural nationalism. It will also further enhance Australia's international intellectual profile by bringing together leading researchers to forge innovative research networks and methodologies to advance the knowledge bases of Chinese intellectual history, Chinese Philosophy and Buddhist Studies, and contribute to building Australian research capacity in these three key areas.Read moreRead less
Changing your mind by changing your brain: An interventionist perspective on cognitive neuroscience. Functional neuroimaging provides a tremendous amount of information about the brain, but what it shows about the mind is less clear. Addressing this fundamental philosophical question requires developing a detailed account of theory-testing in cognitive neuroscience. This project aims to connect neuroimaging to theories of explanation that focus on the way one variable can make a difference to an ....Changing your mind by changing your brain: An interventionist perspective on cognitive neuroscience. Functional neuroimaging provides a tremendous amount of information about the brain, but what it shows about the mind is less clear. Addressing this fundamental philosophical question requires developing a detailed account of theory-testing in cognitive neuroscience. This project aims to connect neuroimaging to theories of explanation that focus on the way one variable can make a difference to another. By linking neuroimaging to facts about manipulable relationships between the brain and the mind, it will also provide a bridge between neuroimaging and complementary technologies for directly intervening on the brain. This, in turn, will provide a platform from which to explore the theoretical and ethical consequences of direct brain manipulation.Read moreRead less