Trace Element Regulation In Neurological Disease: From Molecular Pathogenesis To Translational Impact.
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Neurodegenerative diseases such as dementia and motor neuron disease are a major health burden for Australia and new approaches to treatment are urgently required. Essential trace elements such as copper, zinc and iron show major changes in neurodegneration, however, we do not understand how this drives disease processes. This proposal will develop an innovative 3D ‘brain on a chip’ cell model to probe the role of trace elements in brain pathology and identify exciting new treatments options.
Functional Copper Deficiency Models Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$454,691.00
Summary
Alzheimer's disease is a serious neurodegenerative disease which increases in incidence with age. It affects the quality of life and care required for approximately 160,000 Australians and costs the national economy 6.6 billion dollars per annum. Current therapy is of limited efficacy. Our studies are directed towards testing the hypothesis that a functional deficiency of the essential trace element, copper, occurs in the brain with ageing, and this leads to oxidative stress and death of neurons ....Alzheimer's disease is a serious neurodegenerative disease which increases in incidence with age. It affects the quality of life and care required for approximately 160,000 Australians and costs the national economy 6.6 billion dollars per annum. Current therapy is of limited efficacy. Our studies are directed towards testing the hypothesis that a functional deficiency of the essential trace element, copper, occurs in the brain with ageing, and this leads to oxidative stress and death of neurons associated with Alzheimer's disease. We will use animal and cell culture models to test this hypothesis which is based on promising preliminary data from such models. We believe that beta amyloid, which accumulates in Alzheimer's brains and is believed to be a major part of the pathological mechanism, has a normal role in maintaining copper balance and that this balance is disturbed by ageing or particular mutations. This research should lead to better treatments using drugs which mobilise copper entry into cells.Read moreRead less
Studies On Mechanisms Of Vesicular Trafficking And Catalysis For The Menkes (MNK) Copper-transporting P-type ATPase
Funder
National Health and Medical Research Council
Funding Amount
$363,757.00
Summary
Copper is an essential trace element for all organisms. Copper is needed for many processes including energy metabolism, the making and maintenance of strong bones and arteries with sufficient elasticity, the synthesis of chemical transmitters in the brain and for the reactions which remove toxic Ofree radicalsO. Copper is also used by the proteins involved in important neurological diseases including Alzheimers disease and Omad cowO disease. Menkes disease is an inherited and usually lethal cop ....Copper is an essential trace element for all organisms. Copper is needed for many processes including energy metabolism, the making and maintenance of strong bones and arteries with sufficient elasticity, the synthesis of chemical transmitters in the brain and for the reactions which remove toxic Ofree radicalsO. Copper is also used by the proteins involved in important neurological diseases including Alzheimers disease and Omad cowO disease. Menkes disease is an inherited and usually lethal copper deficiency disorder in humans, and the diverse and detrimental symptoms of this disease related to organs and tissues described above is a stark indicator of the essentiality of copper. We have carried out extensive research on Menkes disease and in particular the Menkes protein which in normal individuals plays a major role in maintaining the copper balance in cells, i.e. enough Cu to satisfy nutritional needs of cells but not too much which causes toxicity. The normal Menkes protein catalyses the transport of Cu across membranes of cells to the areas where it is needed by copper-dependent enzymes which themselves catalyse important chemical reactions. The normal Menkes protein functions as a molecular pump. We have discovered that this protein can OsenseO Cu concentrations in the cell and when these reach potentially toxic levels it can move (traffick) via small vesicles to the plasma membrane which surrounds cells. There it pumps the excess Cu out of the cell and returns to its original location. Our studies are directed to understanding the molecular mechanisms which permit this remarkable protein to achieve a copper balance in living cells. The findings will be of major significance in understanding and treating acquired and inherited diseases involving copper deficiency or copper toxicity.Read moreRead less
Design of Cost-effective Compositionally Complex Alloys. This project aims to develop low-cost and corrosion resistant compositionally complex alloys and associated processes to concurrently achieve high strength and high toughness using an innovative design strategy. The project expects to overcome the major limitations of this new type of alloys, enabling their practical applications in industry, creating new knowledge of materials science. Expected outcomes include commercialisation ready ne ....Design of Cost-effective Compositionally Complex Alloys. This project aims to develop low-cost and corrosion resistant compositionally complex alloys and associated processes to concurrently achieve high strength and high toughness using an innovative design strategy. The project expects to overcome the major limitations of this new type of alloys, enabling their practical applications in industry, creating new knowledge of materials science. Expected outcomes include commercialisation ready new alloys, breakthrough fundamental understanding of the mechanisms and long-term institutional collaboration. This should provide significant benefits, such as enhancement of Australia’s capacity of alloy development and manufacturing and strengthening the country’s world leading position in this area.Read moreRead less
Biocompatible magnesium alloys with specific materials properties. This project aims to develop biocompatible magnesium alloys with highly desirable mechanical properties and degradation on demand, and the fundamental science to achieve the materials properties. Injured human bones often need biomaterials to restore function. This project’s magnesium biomaterials could change the biomaterials field by making implant removal surgery unnecessary, and avoiding the adverse tissue reactions and stres ....Biocompatible magnesium alloys with specific materials properties. This project aims to develop biocompatible magnesium alloys with highly desirable mechanical properties and degradation on demand, and the fundamental science to achieve the materials properties. Injured human bones often need biomaterials to restore function. This project’s magnesium biomaterials could change the biomaterials field by making implant removal surgery unnecessary, and avoiding the adverse tissue reactions and stress shielding typically associated with conventional implanting metals. The outcomes are expected to provide insights in designing biodegradable magnesium alloys and surface coating technology, and generate intellectual properties and advanced biomaterials that will benefit the Australian ageing population.Read moreRead less
The development of lead-free silicon brass for the plumbing industry. The worldwide brass industry is currently undergoing a transition away from lead-containing brass water fittings to lead-free fittings. The transition is driven by concerns surrounding lead-leaching into drinking water. This project is focussed on the development of new lead-free brasses that can be used to manufacture plumbing fittings with superior combinations of processability, performance and cost.
Discovery Early Career Researcher Award - Grant ID: DE160100357
Funder
Australian Research Council
Funding Amount
$345,000.00
Summary
Ultrastable metallic glasses. The aim of this project is to create a new class of amorphous alloy – ultrastable metallic glass – by a relatively simple vapour-deposition route. These materials are expected to exhibit unprecedentedly low energy states and properties of high thermal stability, elastic modulus, strength, and hardness not achievable in metallic glasses produced by conventional routes. These new materials may also provide a platform for addressing the longstanding issues of relaxatio ....Ultrastable metallic glasses. The aim of this project is to create a new class of amorphous alloy – ultrastable metallic glass – by a relatively simple vapour-deposition route. These materials are expected to exhibit unprecedentedly low energy states and properties of high thermal stability, elastic modulus, strength, and hardness not achievable in metallic glasses produced by conventional routes. These new materials may also provide a platform for addressing the longstanding issues of relaxation dynamics in glassy physics. The unique properties of ultrastable metallic glasses are expected to make them useful in a range of applications, including highly wear- and corrosion-resistant coatings on electronics and biomedical devices and components.Read moreRead less