Iron, ferroptosis and the biology of ageing. This project aims to determine how and when regulation of iron is lost. Failing iron metabolism during life may dictate the rate of ageing by driving a newly discovered cell death program. Combining biology, chemistry and physics, this collaborative project aims to transform the understanding of the fundamental mechanisms of biological ageing. Anticipated outcomes include new assays for measuring iron in biology and identification of potential pathway ....Iron, ferroptosis and the biology of ageing. This project aims to determine how and when regulation of iron is lost. Failing iron metabolism during life may dictate the rate of ageing by driving a newly discovered cell death program. Combining biology, chemistry and physics, this collaborative project aims to transform the understanding of the fundamental mechanisms of biological ageing. Anticipated outcomes include new assays for measuring iron in biology and identification of potential pathways that regulate death signaling and lifespan. Outcomes will benefit life sciences and biotechnology industries.Read moreRead less
Iron accumulation in the nematode C.elegans: a model of ageing. This project will investigate the role of biological metals in the process of ageing, the causes of which remain unresolved. The practical outcomes for society are broad; beyond improving understandings of the basic biology of ageing, this study will provide new insight and approaches that can be used to optimise lifespan.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561041
Funder
Australian Research Council
Funding Amount
$347,358.00
Summary
A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are prote ....A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are proteins, interacting with each other and with signal molecules. The next frontier in molecular biology is to identify and quantify these protein interactions. Our two institutions have a very large cohort of biologists whose research on proteins would be greatly facilitated by the Biacore 3000 and the ISS K2.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
Symbiotic transport proteins in legumes. Some plants form a symbiosis with soil bacteria (rhizobia) that convert atmospheric nitrogen to ammonia which is then supplied to the plant. This enables legumes to grow without application of nitrogen-based fertilizer, avoiding environmental problems such as run-off and land degradation, thereby contributing to sustainable agriculture practise. We will investigate the interactions between plant and rhizobia, focusing on identifying genes and proteins wh ....Symbiotic transport proteins in legumes. Some plants form a symbiosis with soil bacteria (rhizobia) that convert atmospheric nitrogen to ammonia which is then supplied to the plant. This enables legumes to grow without application of nitrogen-based fertilizer, avoiding environmental problems such as run-off and land degradation, thereby contributing to sustainable agriculture practise. We will investigate the interactions between plant and rhizobia, focusing on identifying genes and proteins which govern nutrient exchange between the partners and development of the special structures in the roots that house the bacteria. Subsequent manipulation of these genes and proteins may allow us to identify control points and enhance nitrogen fixation.
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Genome Approaches to Investigate Metabolic Coordination in Plant Cells. Metabolism of C and N in legume nodules requires interaction between the symbiotic bacteria and plant organelles, particularly metabolism in plastids and mitochondria. Fixed N is assimilated through the de novo synthesis of purines in both plastids and mitochondria. However, each of the nine pathway enzymes is encoded by a single gene, indicating each protein is targeted to both organelles. Purine metabolism will provide ....Genome Approaches to Investigate Metabolic Coordination in Plant Cells. Metabolism of C and N in legume nodules requires interaction between the symbiotic bacteria and plant organelles, particularly metabolism in plastids and mitochondria. Fixed N is assimilated through the de novo synthesis of purines in both plastids and mitochondria. However, each of the nine pathway enzymes is encoded by a single gene, indicating each protein is targeted to both organelles. Purine metabolism will provide a model to assess the more general occurrence of dual-targeted proteins in plants. The aim is to identify and eventually exploit the signalling mechanism(s) that mediate communication between plastids and mitochondria.Read moreRead less
Is transport of miRNAs essential for plant development? This project will provide knowledge of how a new class of biologically active molecule (micro RNA) regulates expression of genes at sites in the plant that are critical for growth and development. MicroRNAs are believed to influence the size and shape of plants, how rapidly they grow and how well they produce and fill seeds. These molecules are part of a group of bioactive signals that move throughout the plant, functioning like hormones bu ....Is transport of miRNAs essential for plant development? This project will provide knowledge of how a new class of biologically active molecule (micro RNA) regulates expression of genes at sites in the plant that are critical for growth and development. MicroRNAs are believed to influence the size and shape of plants, how rapidly they grow and how well they produce and fill seeds. These molecules are part of a group of bioactive signals that move throughout the plant, functioning like hormones but directly influencing how well critical genes work. Their exploitation holds great promise for manipulating plant performance and enhancing crop yields. Read moreRead less
The effect of nitrogen monoxide on intracellular iron metabolism. We discovered that the crucial signalling molecule nitrogen monoxide (NO) mediates iron (Fe) and glutathione (GSH) release by the transporter MRP1 probably as an NO-Fe-GSH complex [DR(2006) PNAS USA 103:7670-5]. During our current ARC grant we have markedly extended these findings by showing that another molecule, GST Pi and MRP1 form part of a coordinated system that stores and transports NO as complexes of Fe and GSH, markedly e ....The effect of nitrogen monoxide on intracellular iron metabolism. We discovered that the crucial signalling molecule nitrogen monoxide (NO) mediates iron (Fe) and glutathione (GSH) release by the transporter MRP1 probably as an NO-Fe-GSH complex [DR(2006) PNAS USA 103:7670-5]. During our current ARC grant we have markedly extended these findings by showing that another molecule, GST Pi and MRP1 form part of a coordinated system that stores and transports NO as complexes of Fe and GSH, markedly extending NO half-life from milliseconds to hours. This has broad implications for understanding NO activity in many processes which have major vital health implications, including tumour cell killing by macrophages and blood pressure control.Read moreRead less
Navigating flux control through a branched metabolic pathway. This project aims to uncover control points and programmes in the mevalonate pathway, an important cellular metabolic pathway that produces cholesterol and isoprenoids. Knowledge of its regulation is largely restricted to just one enzyme (HMGCR). This project will determine how regulation of the later sterol-producing segment affects the early isoprenoid-segment of the mevalonate pathway; investigate how the two alternate routes to ch ....Navigating flux control through a branched metabolic pathway. This project aims to uncover control points and programmes in the mevalonate pathway, an important cellular metabolic pathway that produces cholesterol and isoprenoids. Knowledge of its regulation is largely restricted to just one enzyme (HMGCR). This project will determine how regulation of the later sterol-producing segment affects the early isoprenoid-segment of the mevalonate pathway; investigate how the two alternate routes to cholesterol synthesis operate and are regulated; and explore a co-ordinated and possibly co-operative transcriptional program. This project is expected to provide valuable knowledge of how cells control these critical lipids, which will ultimately inform better ways to treat diseases of cholesterol excess and defects in this pathway.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