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
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
A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.Read moreRead less
The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these ....The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these subcellular organelles affect free radical damage and aging, using the fruitfly Drosophila melanogaster as a model organism.Read moreRead less
Involvement of cell coupling in vascular function: Development of a computational model. Gap junctions are intercellular channels which enable the production of coordinated responses in multicellular tissues and organs. Blood vessels are comprised of endothelial cells surrounded by smooth muscle cells and gap junctions exist within and between these layers. The present proposal will determine the fundamental role of gap junctions in regulating blood flow and blood pressure. Our data will enable ....Involvement of cell coupling in vascular function: Development of a computational model. Gap junctions are intercellular channels which enable the production of coordinated responses in multicellular tissues and organs. Blood vessels are comprised of endothelial cells surrounded by smooth muscle cells and gap junctions exist within and between these layers. The present proposal will determine the fundamental role of gap junctions in regulating blood flow and blood pressure. Our data will enable us to develop a computational model of the vascular wall and so predict how changes in electrical properties, as occur during pressure changes, can influence blood flow. Since ageing is accompanied by an increase in blood pressure, our results will contribute to a better understanding of blood flow regulation in our ageing population.Read moreRead less
Determinants of metabolic rate in animals. The metabolic rate of an animal represents its fundamental "cost of living" and varies dramatically (>100-fold) between different vertebrate species. We have proposed the "membrane pacemaker theory" to explain this variation and currently this is the only mechanistic explanation of metabolic variation between species. It has received significant international interest. A species metabolic rate and its maximum lifespan are connected but the precise mecha ....Determinants of metabolic rate in animals. The metabolic rate of an animal represents its fundamental "cost of living" and varies dramatically (>100-fold) between different vertebrate species. We have proposed the "membrane pacemaker theory" to explain this variation and currently this is the only mechanistic explanation of metabolic variation between species. It has received significant international interest. A species metabolic rate and its maximum lifespan are connected but the precise mechanistic link between them is unknown. We will investigate the mechanisms underlying the "membrane pacemaker theory" as an explanation of the metabolic rates of vertebrate species and its role in the determination of maximum lifespan.Read moreRead less
Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein function ....Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein functions. By doing so, the project will illuminate how haem oxygenase-1 alters cell functions in a beneficial way. This information will eventually assist in preventing the serious disorders associated with deficiency of haem oxygenase-1. It will also provide the basis for novel treatments to slow down age-associated diseases.Read moreRead less
Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identi ....Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identifying RNA molecules that contribute to quantitative phenotypes including susceptibility to disease. As such, it will directly benefit fundamental science via the discovery and classification of new molecules. Indirectly, it will lead to breakthroughs in biology, and consequently to major medical and pharmaceutical advances in the diagnosis and treatment of genetic disease.Read moreRead less
Identifying the specific structural features of metallothionein that regulate its ability to modulate astrogliosis. This project contributes directly to the Designated National Research Priority 2 and could potentially have a significant impact upon the broader Australian Community by identifying a novel and powerful therapeutic agent based upon metallothionein proteins with the ultimate aim of helping patients who have a brain injury or a neurodegenerative disease. It is important to note that ....Identifying the specific structural features of metallothionein that regulate its ability to modulate astrogliosis. This project contributes directly to the Designated National Research Priority 2 and could potentially have a significant impact upon the broader Australian Community by identifying a novel and powerful therapeutic agent based upon metallothionein proteins with the ultimate aim of helping patients who have a brain injury or a neurodegenerative disease. It is important to note that the partnership between UTAS and Bestenbalt LLC is a critical step in the development of these exciting research discoveries into commercially viable outcomes for the Australian Biotechnology Industry and the broader Australian community.Read moreRead less
Using metallothioneins as a model for understanding cellular and biochemical interactions between neurons and astrocytes within the brain. This research will reveal some of the changes that occur in the relationship between neurons and astrocytes as a consequence injury, aging or disease to the human brain. In national terms, it will contribute to the concerted effort by Australian scientists to understand how and why neurons die following brain injury or in neurodegenerative diseases. These a ....Using metallothioneins as a model for understanding cellular and biochemical interactions between neurons and astrocytes within the brain. This research will reveal some of the changes that occur in the relationship between neurons and astrocytes as a consequence injury, aging or disease to the human brain. In national terms, it will contribute to the concerted effort by Australian scientists to understand how and why neurons die following brain injury or in neurodegenerative diseases. These are significant community issues in both economical and social terms. Furthermore, this research contributes directly to the Designated National Research Priorities by identifying some of the earliest cellular processes associated with aging or disease of the brain, and will provide clues to promoting healthy aging.Read moreRead less