Dynamics of Multiscale Complex Systems. Australia has built a strong position in the science and applications of multiscale phenomena, especially in interdisciplinary fields. The project will advance this position in plasma and biomedical physics by making new discoveries, developing new methods of analyzing such systems, and applying them to achieve practical outcomes. It will underpin Australia's participation in NASA's $600M STEREO mission, and will lead to improved methods and technologies ....Dynamics of Multiscale Complex Systems. Australia has built a strong position in the science and applications of multiscale phenomena, especially in interdisciplinary fields. The project will advance this position in plasma and biomedical physics by making new discoveries, developing new methods of analyzing such systems, and applying them to achieve practical outcomes. It will underpin Australia's participation in NASA's $600M STEREO mission, and will lead to improved methods and technologies for brain function analysis and imaging, which will be commercialized via industry partnerships. It will contribute to national research goals, especially in Breakthrough Science, Frontier Technologies, Smart Information Use, and Promoting Innovation.Read moreRead less
Physics of Self-Organization: From Space Plasmas to Brain Dynamics. Nature displays intricate, self-organized structures and behaviors that often emerge from simple underlying rules. This project will explore and unify fundamental regimes of self-organization, and apply them to explain phenomena in space, plasma, and wave physics, including making key inputs to the international STEREO space mission. In a core initiative, sophisticated tools from these fields will be transfered and adapted to a ....Physics of Self-Organization: From Space Plasmas to Brain Dynamics. Nature displays intricate, self-organized structures and behaviors that often emerge from simple underlying rules. This project will explore and unify fundamental regimes of self-organization, and apply them to explain phenomena in space, plasma, and wave physics, including making key inputs to the international STEREO space mission. In a core initiative, sophisticated tools from these fields will be transfered and adapted to analyze self-organized brain dynamics, leading to the first self-consistent "working brain" model. The results of this innovation will be used to develop new imaging technologies, to probe brain function via the new windows they open, and to exploit them commercially.Read moreRead less
Superfluid helium nanodroplet spectroscopy. Molecules trapped in a helium nanodroplet find themselves in an ultracold liquid environment from which they cannot escape. As such, the molecules are forced to interact and this is studied at a resolution that is unrivaled in condensed phase spectroscopy. This technique will be used to create new materials and study the dynamics behind a large range of chemical processes. The results are expected to lead to a greater understanding of condensed phase c ....Superfluid helium nanodroplet spectroscopy. Molecules trapped in a helium nanodroplet find themselves in an ultracold liquid environment from which they cannot escape. As such, the molecules are forced to interact and this is studied at a resolution that is unrivaled in condensed phase spectroscopy. This technique will be used to create new materials and study the dynamics behind a large range of chemical processes. The results are expected to lead to a greater understanding of condensed phase chemistry and chemical reactions in general.Read moreRead less
Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interaction ....Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interactions and be used as lead compounds for treatments for disease.Read moreRead less
Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.
Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems ar ....Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems are activated as during the process.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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LIM-homeodomain interactions in neuronal development. The loss of central nervous system function, through accident or disease, is devastating for affected individuals and their families. Our current inability to stimulate the regeneration of nervous tissue is a result of the lack of detailed knowledge of the complex processes that must take place, at the molecular and cellular levels, during neuronal development. We are determining how a group of cellular proteins that have key roles in motor n ....LIM-homeodomain interactions in neuronal development. The loss of central nervous system function, through accident or disease, is devastating for affected individuals and their families. Our current inability to stimulate the regeneration of nervous tissue is a result of the lack of detailed knowledge of the complex processes that must take place, at the molecular and cellular levels, during neuronal development. We are determining how a group of cellular proteins that have key roles in motor neuron development interact with each other and with DNA. With this information we are developing reagents that can be used to further probe central nervous system function and may ultimately be used to regenerate damaged nerves.Read moreRead less