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
Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and r ....Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and research skill base. Young scientists will be trained in state-of-the-art research techniques in a cross-disciplinary environment that is the way of future biological research. The project may identify potential drug targets for malaria or other infectious diseases. The Intellectual Property will be protected and commercialised.Read moreRead less
Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel ta ....Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel targets and strategies for treating obesity. The proposed study will also benefit Australian agriculture by providing strategies to improve oil production from plant seeds. Read moreRead less
Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical int ....Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical intervention. In addition, a powerful model system for studies of ER protein aggregation will be established, high-level training in biochemistry and morphometry will be provided, and an international collaboration of the highest calibre will be initiated.Read moreRead less
The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Mic ....The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Microaerobes include some bacteria, archea and protozoa. Realisation of the widespread habitats and importance of microaerophiles, has led recently to a vigorous interest in understanding their physiology. Knowledge of the basic properties of microaerophily has potential applications to Environmental Microbiology, Agriculture, Industrial Microbiology, Veterinary Science and Medicine.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775746
Funder
Australian Research Council
Funding Amount
$102,000.00
Summary
GC/MS facility for medical, bioanalytical and environmental research. The research will contribute to the bioremediation of heavily polluted sites in Sydney and the knowledge gained and the technology developed will be applicable to sites all over the world. Fundamental knowledge in Systems Biology will have applications to advance Australian export industries based on fermentation. Advances in chemical ecology and biotechnology will impact in areas such as contact lenses, implants, therapeutics ....GC/MS facility for medical, bioanalytical and environmental research. The research will contribute to the bioremediation of heavily polluted sites in Sydney and the knowledge gained and the technology developed will be applicable to sites all over the world. Fundamental knowledge in Systems Biology will have applications to advance Australian export industries based on fermentation. Advances in chemical ecology and biotechnology will impact in areas such as contact lenses, implants, therapeutics and water treatment. Probing pituitary hormone action will lead to greater understanding of health issues such as abnormal body composition, obesity and diabetes.Read moreRead less
Defining the Regulatory Pool of Cholesterol in the Mammalian Cell. Heart disease remains the greatest killer of Australians and Alzheimer's disease represents a growing burden in our aging population. The information gained in this project will be invaluable in advancing our understanding of how cholesterol levels are controlled within the cell and will provide the groundwork for further research that can help to identify novel targets for new drugs to fight heart disease and Alzheimer's diseas ....Defining the Regulatory Pool of Cholesterol in the Mammalian Cell. Heart disease remains the greatest killer of Australians and Alzheimer's disease represents a growing burden in our aging population. The information gained in this project will be invaluable in advancing our understanding of how cholesterol levels are controlled within the cell and will provide the groundwork for further research that can help to identify novel targets for new drugs to fight heart disease and Alzheimer's disease.Read moreRead less
Novel mass spectrometry methods to assess cellular oxidative stress. This project will provide fundamental understanding to the biology of cell stress that may lead to novel approaches for treating age-related diseases. It has the potential to have a significant economic and social impact nationally and internationally and provide Australian scientists with new technologies to study challenging issues in biology.
Investigating the molecular function of alpha-Haemoglobin stabilising protein. The research described in this proposal will provide new insights into haemoglobin regulation and redox chemistry in erythrocytes. Deregulation of these processes gives rise to a number of debilitating diseases, including varieties of anaemia and thalassaemia-in Australia it is estimated that 3% of the population could be carriers of b-thalassaemia mutations. Given the contribution of free aHb to the pathology of b-th ....Investigating the molecular function of alpha-Haemoglobin stabilising protein. The research described in this proposal will provide new insights into haemoglobin regulation and redox chemistry in erythrocytes. Deregulation of these processes gives rise to a number of debilitating diseases, including varieties of anaemia and thalassaemia-in Australia it is estimated that 3% of the population could be carriers of b-thalassaemia mutations. Given the contribution of free aHb to the pathology of b-thalassaemia, understanding the specific aHb-binding factor, AHSP is a goal of national significance. In the long term, manipulation of AHSP function through gene therapy may have a direct role in the treatment of thalassaemia.Read moreRead less
The cellular dynamics of lipid droplets: implications for obesity and biodiesel production. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also identify novel com ....The cellular dynamics of lipid droplets: implications for obesity and biodiesel production. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also identify novel compounds and strategies for treating obesity. The proposed study will also benefit Australian agriculture and energy industry by providing strategies to improve the production of plant oil and biodiesel. Read moreRead less