Protein-protein interactions in amyloid deposits. The aggregation of specific proteins to form insoluble amyloid fibrils is characteristic of several age-related diseases such as type-II diabetes, Alzheimer's disease and Parkinson's disease. In vivo amyloid deposits also contain three prominent non-fibrillar protein components, namely serum amyloid P component, apolipoprotein E and alpha1-antichymotrypsin. These non-fibrillar amyloid components bind to a wide variety of amyloid fibrils, irresp ....Protein-protein interactions in amyloid deposits. The aggregation of specific proteins to form insoluble amyloid fibrils is characteristic of several age-related diseases such as type-II diabetes, Alzheimer's disease and Parkinson's disease. In vivo amyloid deposits also contain three prominent non-fibrillar protein components, namely serum amyloid P component, apolipoprotein E and alpha1-antichymotrypsin. These non-fibrillar amyloid components bind to a wide variety of amyloid fibrils, irrespective of the nature of the protein constituent. This proposal is to identify the structural basis for this recognition process, the capacity of non-fibrillar components to cross-link amyloid fibrils to form networks and the influence of these interactions on amyloid fibril cytotoxicity.Read moreRead less
Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of hea ....Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of healthy, genetically intact sperm. This project draws together an international team to investigate a phenomenon with implications for new understanding of normal developmental processes and the response of cells/tissues to disease conditions.Read moreRead less
The effects of alpha-2-macroglobulin on amyloid formation and toxicity. The expected outcomes will provide major advances in understanding how the abundant human blood protein alpha-2-macroglobulin influences the formation of protein aggregates that underpin a number of serious diseases (e.g. Alzheimer's disease). The linkages involved are of the highest calibre and will give the Fellowship holder a unique opportunity for training in environments that are truly internationally leading-edge. Fur ....The effects of alpha-2-macroglobulin on amyloid formation and toxicity. The expected outcomes will provide major advances in understanding how the abundant human blood protein alpha-2-macroglobulin influences the formation of protein aggregates that underpin a number of serious diseases (e.g. Alzheimer's disease). The linkages involved are of the highest calibre and will give the Fellowship holder a unique opportunity for training in environments that are truly internationally leading-edge. Furthermore, the very high novelty and broad significance of this work indicate that it will produce high-impact publications which will tangibly assist Australia being recognized as a major contributor to international research outcomes of the highest quality.Read moreRead less
A novel role for SMG-1 protein kinase in stress granule formation and the stress response. Humans are constantly exposed to agents in the environment that threaten the integrity of their cells and increases the risk of cancer and other pathologies. Cells have developed repair mechanisms to cope with damage to their DNA and avoid long term effects. The emphasis in this application is to investigate the mechanisms by which stress affects the transcriptional machinery in the cell. A description of ....A novel role for SMG-1 protein kinase in stress granule formation and the stress response. Humans are constantly exposed to agents in the environment that threaten the integrity of their cells and increases the risk of cancer and other pathologies. Cells have developed repair mechanisms to cope with damage to their DNA and avoid long term effects. The emphasis in this application is to investigate the mechanisms by which stress affects the transcriptional machinery in the cell. A description of the processes involved will assist in understanding how specific disease states arise and will provide a means of devising compounds/drugs to assist the response to stress. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561169
Funder
Australian Research Council
Funding Amount
$188,000.00
Summary
Facility for multidimensional fractionation of complex biological mixtures. Acquisition of multidimensional fractionation equipment will allow researchers to separate proteins from complex mixtures, and to compare whole protein profiles of multiple samples. This will permit correlation of specific protein changes associated with infection or disease, a major focus of post-genomic programs of research. The equipment will also provide identification of the key differentiating proteins using mini ....Facility for multidimensional fractionation of complex biological mixtures. Acquisition of multidimensional fractionation equipment will allow researchers to separate proteins from complex mixtures, and to compare whole protein profiles of multiple samples. This will permit correlation of specific protein changes associated with infection or disease, a major focus of post-genomic programs of research. The equipment will also provide identification of the key differentiating proteins using minimal material. Numerous world-class projects and researchers will be able to move more rapidly and reliably from crude cell extracts to identifiable markers, and maintain their competitive positions the recognition of key targets in drug design, disease diagnosis and vaccine development.Read moreRead less
Establishing the role of alpha-2-macroglobulin in quality control of extracellular protein folding. The expected outcomes will provide important advances in understanding the role of alpha-2-macroglobulin (A2M) in maintaining the normal structure/function of extracellular proteins. This information may ultimately aid in the design of agents to be used to clear the body of pathological protein aggregates - potentially providing a direct economic benefit to Australia. The high novelty and broad si ....Establishing the role of alpha-2-macroglobulin in quality control of extracellular protein folding. The expected outcomes will provide important advances in understanding the role of alpha-2-macroglobulin (A2M) in maintaining the normal structure/function of extracellular proteins. This information may ultimately aid in the design of agents to be used to clear the body of pathological protein aggregates - potentially providing a direct economic benefit to Australia. The high novelty and broad significance of this work indicate that it will produce high-impact publications which will tangibly assist Australia being recognized as a major contributor to world research outcomes. This project will also provide a direct social benefit by training research students with the skills necessary to further the development of biological research in Australia.Read moreRead less
Discovering Mechanisms for Quality Control of Extracellular Protein Folding. The expected outcomes will provide important advances in understanding of how the mammalian body maintains the normal structure/function of extracellular proteins. This information may ultimately aid in the design of agents to be used to clear the body of pathological protein aggregates - potentially providing a direct economic benefit to Australia. The high novelty and broad significance of this work indicate that it w ....Discovering Mechanisms for Quality Control of Extracellular Protein Folding. The expected outcomes will provide important advances in understanding of how the mammalian body maintains the normal structure/function of extracellular proteins. This information may ultimately aid in the design of agents to be used to clear the body of pathological protein aggregates - potentially providing a direct economic benefit to Australia. The high novelty and broad significance of this work indicate that it will produce high-impact publications which will tangibly assist Australia being recognized as a major contributor to world research outcomes. This project will also provide a direct social benefit by training research students with the skills necessary to further the development of biological research in Australia. Read moreRead less
Pheromone evolution and ecology in insects on intra- and inter-specific scales. The study of pheromones is important because so many insect pests use them as part of their reproductive life cycle, increasing their potential to cause damage to crops and other natural products. My research will improve our understanding of the evolution of pheromones and communication by smell, a subject that has been largely neglected by evolutionary biologists. More specifically, by identifying the ecological fa ....Pheromone evolution and ecology in insects on intra- and inter-specific scales. The study of pheromones is important because so many insect pests use them as part of their reproductive life cycle, increasing their potential to cause damage to crops and other natural products. My research will improve our understanding of the evolution of pheromones and communication by smell, a subject that has been largely neglected by evolutionary biologists. More specifically, by identifying the ecological factors that influence pheromone evolution, the research will help to assess the long-term consequences of the control measures currently used against such pests and, in particular, will have direct applications to the prevention of damage to Australian pine plantations by the invasive five-spined bark beetle, Ips grandicollis. Read moreRead less
Phylogeny and radiation of flatworm ectoparasites from marine fish using morphology and genetics, with novel approaches to identify pathogenic species. Fish flukes (flatworm parasites) with direct lifecycles can weaken and kill captive fish and threaten lucrative industries like finfish aquaculture and public aquaria in Australia and globally. Traditional approaches and molecular techniques will identify monogenean flukes in a family containing known pathogenic species distributed worldwide. K ....Phylogeny and radiation of flatworm ectoparasites from marine fish using morphology and genetics, with novel approaches to identify pathogenic species. Fish flukes (flatworm parasites) with direct lifecycles can weaken and kill captive fish and threaten lucrative industries like finfish aquaculture and public aquaria in Australia and globally. Traditional approaches and molecular techniques will identify monogenean flukes in a family containing known pathogenic species distributed worldwide. Knowledge of fish disease is paramount for quarantine, risk assessments for import/export and for managing pathogen outbreaks in aquaculture. Benefits include: economic/social improvements in regional/rural Australia where fish farms are expanding; international excellence and core research training in fish parasitology; profitable, exportable expertise; knowledge of endemic and shared pathogens.Read moreRead less
Cell-free immune reactions and suppression. Insects pests and insect vectors of diseases are managed by toxic substances, but insects have a cunning ability to persist. How pesticide-tolerant insect pests recognise and inactivate chemical and biological toxins is poorly understood. While vertebrates with a closed circulatory system use coagulation reactions mainly for wound-healing, invertebrates employ cell-free aggregation reactions for the sequestration and inactivation of potentially damagin ....Cell-free immune reactions and suppression. Insects pests and insect vectors of diseases are managed by toxic substances, but insects have a cunning ability to persist. How pesticide-tolerant insect pests recognise and inactivate chemical and biological toxins is poorly understood. While vertebrates with a closed circulatory system use coagulation reactions mainly for wound-healing, invertebrates employ cell-free aggregation reactions for the sequestration and inactivation of potentially damaging objects and substances. We use insect plasma to dissect recognition and inactivation of damaging objects and substances with the aim to understand tolerance and its inhibition to design novel strategies in delaying tolerance to pesticides in insect pests.Read moreRead less