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
Investigations of signals involved in redox-regulation of carbon storage. This project seeks molecular understanding of signals optimising storage processes in plants in response to nutrient supply and environmental stress. Discovering regulatory signals that control carbon storage and yield will maintain Australia's international reputation in this field of research and may provide technical opportunities to improve crops in healthy or stressful environments. This is an issue of increasing impo ....Investigations of signals involved in redox-regulation of carbon storage. This project seeks molecular understanding of signals optimising storage processes in plants in response to nutrient supply and environmental stress. Discovering regulatory signals that control carbon storage and yield will maintain Australia's international reputation in this field of research and may provide technical opportunities to improve crops in healthy or stressful environments. This is an issue of increasing importance especially in the context of global warming. 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
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
The Effect of Nitrogen Monoxide on Intracellular Iron Metabolism. For the first time, we discovered that nitric oxide (NO) is actively transported from cells by a protein that is known to also transport glutathione (GSH). This is important, as NO was thought to passively diffuse from cells. Active transport overcomes the problems of diffusion which is inefficient and non-targeted. Moreover, NO is released as a complex with iron and GSH which markedly increases its half-life. These findings have ....The Effect of Nitrogen Monoxide on Intracellular Iron Metabolism. For the first time, we discovered that nitric oxide (NO) is actively transported from cells by a protein that is known to also transport glutathione (GSH). This is important, as NO was thought to passively diffuse from cells. Active transport overcomes the problems of diffusion which is inefficient and non-targeted. Moreover, NO is released as a complex with iron and GSH which markedly increases its half-life. These findings have broad implications for understanding the activity of NO in many processes which have major health implications, including tumour cell killing by macrophages, blood pressure etc.Read moreRead less
The effect of nitrogen monoxide on intracellular iron metabolism. During our current ARC grant we discovered a novel relationship between energy metabolism and NO-mediated Fe efflux and showed that glutathione (GSH) is vital for this release mechanism (DR5,6). Intriguingly, this transport process is part of the cytotoxic effector machinery of activated macrophages against tumours, and requires further elucidation. We also showed that CO affects Fe metabolism by binding to Fe, and CO may modulate ....The effect of nitrogen monoxide on intracellular iron metabolism. During our current ARC grant we discovered a novel relationship between energy metabolism and NO-mediated Fe efflux and showed that glutathione (GSH) is vital for this release mechanism (DR5,6). Intriguingly, this transport process is part of the cytotoxic effector machinery of activated macrophages against tumours, and requires further elucidation. We also showed that CO affects Fe metabolism by binding to Fe, and CO may modulate NO's function. We will:-
(1) Examine if NO-mediated Fe release results in GSH efflux
(2) Identify the mechanism of NO-mediated Fe efflux.
(3) Assess the effect of inducing haem oxygenase 1 on Fe metabolism
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A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
How do cells regulate redox environment at the subcellular level? Most organisms live in an aerobic environment that subjects their cells to reactive oxygen species. Reactive oxygen species have been proposed to lead to ageing, and in many diseases the balance between oxidising and reducing conditions (the redox environment) is perturbed. This research will identify how different cellular structures sense and maintain this redox homeostasis, not just in the whole cell, but within the different ....How do cells regulate redox environment at the subcellular level? Most organisms live in an aerobic environment that subjects their cells to reactive oxygen species. Reactive oxygen species have been proposed to lead to ageing, and in many diseases the balance between oxidising and reducing conditions (the redox environment) is perturbed. This research will identify how different cellular structures sense and maintain this redox homeostasis, not just in the whole cell, but within the different organelles in the cell. The work will help identify which cell compartments and processes are affected in different disease states and provide a fundamental understanding of how cells coordinate their different organelles to maintain the balance between oxidising and reducing conditions.Read moreRead less
Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a fra ....Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a framework to test regulatory network models and to analyse the molecular basis of interactions between control systems. This research will eventually provide the ability to predict how cells respond to drugs and other environmental stimuli.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