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
Cation Ordering - A Strategy to Prepare Multiferroic Oxides. This project will produce new families of functional metal oxides with technologically relevant properties, especially multiferroic behavior. Such materials are highly sort-after in the rapidly emerging field of spintronics. Through comprehensive experimental studies of a number of such materials this project will enhance the ability of industry to develop new and improved materials.
Light on a nanoscale: channelling energy through space and time to control neuronal activity. Quantum-mechanical effects of energy transfer and resonance will be harnessed to yield ultrabright nanoscale light sources. Research will unveil the intricate interplay between energy harvesting, transferring and emitting centres designed so that the flow of energy exhibits a directed character. This focussed intense energy will produce abundant visible photons from infrared light. Genetically engineere ....Light on a nanoscale: channelling energy through space and time to control neuronal activity. Quantum-mechanical effects of energy transfer and resonance will be harnessed to yield ultrabright nanoscale light sources. Research will unveil the intricate interplay between energy harvesting, transferring and emitting centres designed so that the flow of energy exhibits a directed character. This focussed intense energy will produce abundant visible photons from infrared light. Genetically engineered cells able to be stimulated optically by using an optogenetics method will be illuminated by our nanoscale light causing modulation of cell activity. This new capability will enable remote control of neuronal activity in specific circuits within the nervous system without the limitation of surgically inserted optical fibres.Read moreRead less
Nickel(III) Oxyhydroxide (NiOOH) as a Positive Electrode Material in Primary Cells. In recent years, the demands put on batteries has increased due to the development of sophisticated portable electronic devices. With the currently available primary battery systems finding it difficult to cope with these demands, there is considerable incentive to develop an improved system with an appropriate capability. This project focuses on nickel(III) oxyhydroxide (NiOOH) as a cathode material. NiOOH is us ....Nickel(III) Oxyhydroxide (NiOOH) as a Positive Electrode Material in Primary Cells. In recent years, the demands put on batteries has increased due to the development of sophisticated portable electronic devices. With the currently available primary battery systems finding it difficult to cope with these demands, there is considerable incentive to develop an improved system with an appropriate capability. This project focuses on nickel(III) oxyhydroxide (NiOOH) as a cathode material. NiOOH is used widely in rechargeable battery systems, where it performs adequately even under severe discharge conditions. However, in primary battery systems, NiOOH suffers from self discharge. This project aims to use the performance capabilities of NiOOH in a primary system, by investigating ways to improve its stability. The benefits for Delta EMD will be protection of their existing business, as well as opening the door to the commercial manufacture of an advanced export material.Read moreRead less
Capacitance Fade Mechanisms in Carbon-Based Supercapacitors. Energy storage is of significant importance to the global community. This project addresses certain performance issues concerning prolonged energy storage in supercapacitors, which are an emerging technology in the electronics industry. CAP-XX is Australia's only manufacturer of supercapacitors, and the improvements to their products that will result from this work, will lead to significant returns to them and the Australian economy.
Electrochemically activated solid state chemistry: A new synthetic avenue. This project aims to validate a new solid state synthetic route discovered in our group by understanding the reaction mechanism and experimenting with the parameter space of reaction variables. The discovery of a new solid state synthetic route opens up a world of possibility for the generation of new materials with a diverse range of potential functions and applications. The fundamental understanding of the reaction mech ....Electrochemically activated solid state chemistry: A new synthetic avenue. This project aims to validate a new solid state synthetic route discovered in our group by understanding the reaction mechanism and experimenting with the parameter space of reaction variables. The discovery of a new solid state synthetic route opens up a world of possibility for the generation of new materials with a diverse range of potential functions and applications. The fundamental understanding of the reaction mechanism will enable the rapid and widespread use of this synthetic route.Read moreRead less
Hydrogen storage materials for energy conversion applications. For a clean environment, the ideal synthetic fuel is hydrogen because it is lightweight, highly abundant and its oxidation product (water) is environmentally benign. However, the effective storage of hydrogen remains a scientific challenge. This project aims to develop innovative materials with high hydrogen storage capacity and long cycle life, including new composite hydrides, catalysed metal hydrides and various nanotubes. The exp ....Hydrogen storage materials for energy conversion applications. For a clean environment, the ideal synthetic fuel is hydrogen because it is lightweight, highly abundant and its oxidation product (water) is environmentally benign. However, the effective storage of hydrogen remains a scientific challenge. This project aims to develop innovative materials with high hydrogen storage capacity and long cycle life, including new composite hydrides, catalysed metal hydrides and various nanotubes. The expected outcome is the achievement of high reversible hydrogen storage capacity to meet all the demands required for energy conversion applications, in particular, for hydrogen storage/fuel-cell vehicular applications.Read moreRead less
Surface Processing of Photo-Sensitive Semiconducting Oxides for Solar-Hydrogen. Aim: To enhance the performance of titania-based semiconducting photo-electrodes for the generation of hydrogen from water using sunlight. Means: Engineering of the surface and near-surface layers so as to increase photo-sensitivity and reactivity with water. Significance: Success will provide the key functional component of photo-electrochemical cells for the mass production of renewable and clean hydrogen. In ....Surface Processing of Photo-Sensitive Semiconducting Oxides for Solar-Hydrogen. Aim: To enhance the performance of titania-based semiconducting photo-electrodes for the generation of hydrogen from water using sunlight. Means: Engineering of the surface and near-surface layers so as to increase photo-sensitivity and reactivity with water. Significance: Success will provide the key functional component of photo-electrochemical cells for the mass production of renewable and clean hydrogen. Innovation: For the first time, the properties controlling photo-sensitivity (defect disorder; charge transport; and chemically-induced, local, surface electric fields) will be modified. Outcomes: Technologies for the production of fuel (hydrogen) using renewable energy (solar energy) and a renewable resource (water).
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