Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins ....Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins of interest by conventional proteomic methods. The establishment of SELDI-MS as a viable tool for cell proteomics would open new opportunities to understand a broad range of cellular functions at the level of protein expression.Read moreRead less
Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preven ....Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preventative health perspective, the investigation of platelet calcium signalling will greatly accelerate the development of new pharmaceuticals to tackle acute and chronic cardiovascular diseases, such as stroke, heart attack and artherosclerosis. Read moreRead less
Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nan ....Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nanotechnology would therefore benefit from this work by basing their designs on the principles behind the mechanism of the bacterial motor. This research is also of interest for veterinary science, as motility by flagellar motor is a key virulence factor of common animal pathogens associated with, for example, listeriosis and gastroenteritis.Read moreRead less
Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operati ....Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operation and seeking cures for diseases caused by their malfunction. This project aims to develop accurate ion-protein-water interactions for permeation models based on stochastic and molecular dynamics simulations using both classical and quantum mechanical methods.Read moreRead less
Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production ....Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production and the structure/function of the solar powerhouse of plants (chloroplasts), and addresses fundamental questions at the interface of biology and physics. The research explores chloroplasts as a manifestation of the all-pervading Second Law of Thermodynamics, advancing Australia's contribution to basic science and helping to train researchers.Read moreRead less
Tail-anchored membrane proteins: prediction, targeting, assembly and function. Using computer-based searches of genome sequence data, we now have a complete list of tail-anchored membrane proteins in the yeast Saccharomyces cerevisiae. These include a number of essential proteins, such as SNAREs and TOM proteins responsible for building cellular membranes in all organisms, including man. Of the additional protein sequences discovered in the search, 8 represent proteins of known function while 19 ....Tail-anchored membrane proteins: prediction, targeting, assembly and function. Using computer-based searches of genome sequence data, we now have a complete list of tail-anchored membrane proteins in the yeast Saccharomyces cerevisiae. These include a number of essential proteins, such as SNAREs and TOM proteins responsible for building cellular membranes in all organisms, including man. Of the additional protein sequences discovered in the search, 8 represent proteins of known function while 19 are novel. We propose to study the subcellular location of these 19 novel proteins, and solve how they are targeted to and inserted in membranes. We will also investigate the function of the newly-discovered proteins.Read moreRead less
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
Cell biology of gastric acid secretion. This research will result in a better understanding of the membrane structures in cells. In turn, this information could be exploited to manipulate ion transport, uptake, secretion of biological molecules, signal transduction events and the delivery and uptake of drugs in a number of disease situations thus leading to more effective therapies.
Furthermore, this work will utilise and develop state-of-the-art technologies, contributing to national competiti ....Cell biology of gastric acid secretion. This research will result in a better understanding of the membrane structures in cells. In turn, this information could be exploited to manipulate ion transport, uptake, secretion of biological molecules, signal transduction events and the delivery and uptake of drugs in a number of disease situations thus leading to more effective therapies.
Furthermore, this work will utilise and develop state-of-the-art technologies, contributing to national competitiveness in this area. A number of students and postdoctoral fellows will be trained as a consequence of working on this project
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What limits CO2 diffusion inside leaves? Dissecting the diffusion path with Arabidopsis mutants. Human induced increase in atmospheric carbon dioxide is now generally accepted as contributing to global warming. Forecasting our future impact relies on models of terrestrial photosynthesis which use a signature in the atmosphere created by plants when they discriminate against the heavy stable isotope of carbon during photosynthesis. Discrimination between isotopes is affected by carbon dioxide dif ....What limits CO2 diffusion inside leaves? Dissecting the diffusion path with Arabidopsis mutants. Human induced increase in atmospheric carbon dioxide is now generally accepted as contributing to global warming. Forecasting our future impact relies on models of terrestrial photosynthesis which use a signature in the atmosphere created by plants when they discriminate against the heavy stable isotope of carbon during photosynthesis. Discrimination between isotopes is affected by carbon dioxide diffusion within leaves and key steps in this process will be identified through the use of Arabidopsis mutants. Better representation of this process in models will improve estimates of terrestrial photosynthesis and climate change forecastsRead moreRead less
Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics ....Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics of MscL, the prototype MS channel, using electronparamagnetic resonance spectroscopy and molecular dynamics simulations in combination with the patch clamp technique. The aim of the project is to elucidate the molecular principles underlying the function of MS channels, which is of fundamental importance for understanding of the biophysics and physiology of mechanosensory transduction throughout the biological world.Read moreRead less