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Mechanisms Of Proteolysis Of Proteins Containing Oxidised Amino Acids
Funder
National Health and Medical Research Council
Funding Amount
$406,320.00
Summary
There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related d ....There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related diseases, such as Alzheimer s disease and other neurological disorders, are also claimed to be associated with deranged protein oxidation, and accumulation of oxidised products. There is clear evidence that certain defensive mechanisms, such as those acting to remove invading organisms and clear wounds, are also associated with an enhanced production of oxidised proteins. Perhaps the most important component of defense against oxidised proteins is their removal by complete breakdown to constituent components, and excretion. Normally, the machinery for breakdown of proteins is in vast excess over the required rate of degradation. However, clearly in these conditions of accumulation of oxidised proteins, this is no longer the case, or no longer suffices. Mechanisms by which oxidised proteins are degraded are poorly understood, and quite controversial. Therefore, the present studies bring to bear a new approach to studying this issue, which has been developed by the applicants. The aim is to reveal mechanisms involved in the breakdown of proteins containing oxidised amino acids, both in cellular systems, and in vivo. Such an understanding may allow us to envisage how to remove oxidised proteins by therapeutic means and therefore interfere with the development of age-related diseases such as Alzheimer s disease and cataract formation and the diseases of the blood vessels associated with attack and stroke.Read moreRead less
Mechanisms Of Oxidised Protein Accumulation In Ageing Cells
Funder
National Health and Medical Research Council
Funding Amount
$429,000.00
Summary
Australia has one of the world's most rapidly ageing populations. It is estimated that in 30 years time over 30% of the population will be over 65; many will suffer from a debilitating, age-related disease. The diseases of ageing represent one of the major health challenges this century. Despite their increasing incidence, our understanding of the underlying causes is limited. A common feature is the accumulation of damaged proteins in cells and tissues. Damaged proteins are usually broken down ....Australia has one of the world's most rapidly ageing populations. It is estimated that in 30 years time over 30% of the population will be over 65; many will suffer from a debilitating, age-related disease. The diseases of ageing represent one of the major health challenges this century. Despite their increasing incidence, our understanding of the underlying causes is limited. A common feature is the accumulation of damaged proteins in cells and tissues. Damaged proteins are usually broken down by the cells and replaced, but in many age-related diseases this process fails. The most common source of protein damage is attack by oxygen-derived free radicals. These are by-products of our body's need for oxygen and can originate from atmospheric pollutants. Oxygen rusts metal, makes fat go rancid and can cause irreparable damage to proteins and other biological molecules. Free radical damage contributes to the development of many age-related diseases such as atherosclerosis and neurodegenerative diseases such as Alzheimer's disease. The accumulation of damaged proteins can cause cell death. Our knowledge of the mechanisms by which cells remove proteins damaged by oxygen and the reasons for their accumulation is limited. In this project we will use a novel technique we have developed to generate oxidised proteins in ageing cells. We will identify cellular mechanisms required for the efficient removal of damaged proteins and those mechanisms which fail in ageing cells. We will focus on a group of proteins which protect damaged proteins from aggregating and accumulating and we will examine how we can prevent the accumulation of oxidised proteins by stimulating the body s defence mechanisms. Since the population of Australia is ageing, diseases of ageing are going to consume an increasing amount of the national health budget. A better knowledge of these cellular mechanisms will allow us to design effective prevention and treatment strategies which are at present lacking.Read moreRead less
All-Metal Nanoporous Materials as Highly Active Electrocatalysts. This project aims to create new avenues for well-controlled large-scale synthesis of hierarchical nanoporous platinum-based architectures, and develop applications for the resultant new electrocatalysts. Developing novel high-performance, low-cost, and long-life electrode catalysts can improve the efficiency, cost, and durability of energy conversion technology. The project plans to use the unique properties of well-defined nanoar ....All-Metal Nanoporous Materials as Highly Active Electrocatalysts. This project aims to create new avenues for well-controlled large-scale synthesis of hierarchical nanoporous platinum-based architectures, and develop applications for the resultant new electrocatalysts. Developing novel high-performance, low-cost, and long-life electrode catalysts can improve the efficiency, cost, and durability of energy conversion technology. The project plans to use the unique properties of well-defined nanoarchitectures to reduce platinum content and to improve electrocatalytic performance. Nanoporous systems in electrocatalysts can provide more active sites and effective surface permeability, which should enhance catalytic activity. Project outcomes may also contribute to our understanding of the relationships among morphologies, pore structures, surface atomic structures and catalytic activities to guide the development of other kinds of high performance nanoporous catalysts.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100229
Funder
Australian Research Council
Funding Amount
$230,000.00
Summary
Carbon-free high temperature vacuum sintering facility. This facility will provide an extremely clean sintering environment for development of advanced materials free from imperfections for applications which range from energy conversion to medical components. It will ensure that Australia is an important international leader in both fundamental research and industrial innovation.
Optimising experimental design for robust product development: a case study for high-efficiency energy generation. This project tackles key mathematical challenges to provide a powerful new methodology and tool for optimal product design, making smarter use of limited information, minimising costly trials, shortening the product cycle, and boosting the competitiveness of both the Australian manufacturing and alternative energy production industries.
Doped metal perovskites for electrocatalysis. This project aims to discover and design perovskite metal-oxide electrocatalyst materials and develop electrocatalytic methods for efficiently driving the oxygen evolution reaction and the oxygen reduction reaction. These are the two most crucial reactions in sustainable energy cycles involving water, hydrogen and oxygen. The project’s anticipated advances in electrocatalysis efficiency for these two reactions will benefit sustainable energy technolo ....Doped metal perovskites for electrocatalysis. This project aims to discover and design perovskite metal-oxide electrocatalyst materials and develop electrocatalytic methods for efficiently driving the oxygen evolution reaction and the oxygen reduction reaction. These are the two most crucial reactions in sustainable energy cycles involving water, hydrogen and oxygen. The project’s anticipated advances in electrocatalysis efficiency for these two reactions will benefit sustainable energy technologies such as fuel cells, metal air batteries and water splitting.Read moreRead less
Non-precious fuel cell cathode catalysts from carbon-based nanohybrids: a computational to experimental quest. This joint computational-experimental project will address significant problems including high cost, limited availability and poor performance in traditional platinum-based fuel cell technology. The outcomes are expected to help address global energy problems through the development of inexpensive fuel cell catalysts based on carbon nanohybrids.
Metal-free catalysts for clean production of energy and hydrogen peroxide. This project aims to create novel metal-free carbon-based catalysts to replace the scarce and expensive noble metal catalysts. Noble metal catalysts are needed for clean production of electricity by fuel cells or hydrogen peroxide from hydrogen and oxygen gases. A combined theoretical and experimental approach will be developed for controlled synthesis of heteroatom-doped carbon catalysts and to improve our understanding ....Metal-free catalysts for clean production of energy and hydrogen peroxide. This project aims to create novel metal-free carbon-based catalysts to replace the scarce and expensive noble metal catalysts. Noble metal catalysts are needed for clean production of electricity by fuel cells or hydrogen peroxide from hydrogen and oxygen gases. A combined theoretical and experimental approach will be developed for controlled synthesis of heteroatom-doped carbon catalysts and to improve our understanding of the catalytic mechanism and structure-activity relationship for the novel carbon catalysts. The project is expected to lay fundamental groundwork for a new paradigm in carbon-based catalysts that should be of considerable significance for energy and chemical production in a clean and cost effective way.Read moreRead less
Development of high efficiency nanocatalysts using novel electron beam fabrication and imaging techniques. This project will develop a new approach for fabricating and studying nanocatalysts based on our expertise in electron beam induced deposition (EBID) of nanostructured materials and environmental scanning electron microscopy (ESEM). ESEM will be used to conduct unique, time-resolved studies of nano-scale, catalysed chemical reactions at elevated temperatures and pressures. The project will ....Development of high efficiency nanocatalysts using novel electron beam fabrication and imaging techniques. This project will develop a new approach for fabricating and studying nanocatalysts based on our expertise in electron beam induced deposition (EBID) of nanostructured materials and environmental scanning electron microscopy (ESEM). ESEM will be used to conduct unique, time-resolved studies of nano-scale, catalysed chemical reactions at elevated temperatures and pressures. The project will advance fundamental understanding and applicability of EBID, ESEM and nanocatalysis. It will yield novel, highly efficient, industrially relevant nanocatalysts for the production of renewable (green) and low emission (clean) energy, with particular applications in hydrogen fuel cells and the catalytic oxidation of carbon monoxide.Read moreRead less