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
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
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.
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
New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. P ....New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. Plastic is present everywhere in human life, but its manufacture and disposal have a strong negative impact on the environment; the new materials manufactured in this project are viable alternatives to plastics, and are sustainable from a production and disposal point of view.Read moreRead less
Living on the edge: how do Australian plants cope with extreme temperature? Of all the climatic factors determining species distributions, temperature is arguably the most important. It is extremes – rather than averages – that drive species evolution. So it is concerning that although extreme temperature events are increasing in frequency and intensity little is known about the breadth of thermal tolerance of plants from extreme environments. This information is crucial to understand species di ....Living on the edge: how do Australian plants cope with extreme temperature? Of all the climatic factors determining species distributions, temperature is arguably the most important. It is extremes – rather than averages – that drive species evolution. So it is concerning that although extreme temperature events are increasing in frequency and intensity little is known about the breadth of thermal tolerance of plants from extreme environments. This information is crucial to understand species distribution and survival under future climate regimes. This project will ascertain the thermal breadth of Australian species growing in situ and under controlled environments. The project will contribute to development of effective conservation, restoration and rehabilitation plans for Australian native plant communities. Read moreRead less
Life, living and livelihoods in satellite cities: new urban forms in India . This project aims to assess the success of satellite cities, conceived as possible solutions to the urgent challenge of rapid urban growth in today’s megacities. Through an ethnography of an Indian satellite city, Mahindra World City, this project aims to generate knowledge on new urban formations and the consequences of experiments in urban development for different socio-economic groups. Understanding the lived experi ....Life, living and livelihoods in satellite cities: new urban forms in India . This project aims to assess the success of satellite cities, conceived as possible solutions to the urgent challenge of rapid urban growth in today’s megacities. Through an ethnography of an Indian satellite city, Mahindra World City, this project aims to generate knowledge on new urban formations and the consequences of experiments in urban development for different socio-economic groups. Understanding the lived experiences of residents/workers in satellite cities aims to form a robust evidence base for research driven dialogue with policy makers, planners and developers. Lessons derived are expected to inform policy and practice as to how to achieve wellbeing for urban residents, while providing indications of Asia’s urban futures.Read moreRead less