Electric field induced surface attachment and detachment of proteins. Microarrays are revolutionising the diagnosis of disease by enabling large amounts of data on genetics and protein expression to be obtained from one sample. Biosensors for diseases and toxins rely on the same mechanism, namely attachment of biological macromolecules to a surface. We propose a new method for controlling the attachment by micromachining an electrode system to apply an electric field to chosen sites. Ultimately ....Electric field induced surface attachment and detachment of proteins. Microarrays are revolutionising the diagnosis of disease by enabling large amounts of data on genetics and protein expression to be obtained from one sample. Biosensors for diseases and toxins rely on the same mechanism, namely attachment of biological macromolecules to a surface. We propose a new method for controlling the attachment by micromachining an electrode system to apply an electric field to chosen sites. Ultimately microelectronic engineering methods will be used. This will give control over the attachment process with potential benefits of orienting attaching molecules, minimising non-specific attachment and enriching diagnostics by enabling interrogation of the force of attachment.Read moreRead less
Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the a ....Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the area of the Research Priority Goal: Breakthrough Science. Postgraduate research students will be trained in sophisticated state-of-the-art theoretical and synthetic chemical methodologies. The project will enhance Australia's research capability in biological (inorganic) chemistry and promote Australia's standing in the International research community.Read moreRead less
Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory ....Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory nervous system. Read moreRead less
Biomolecular films on silicon substrates. Construction of hybrid carbon-silicon devices in which molecular organic molecular films are covalently linked to silicon wafers. Biomolecular nanostructures on silicon wafers can be studied using unique impedance spectroscopy instrumentation that we have developed as well as X-ray and neutron reflectometry. The system will be used to study a variety of molecular films as well as molecularly tethered lipid bilayer membranes that mimic aspects of cell mem ....Biomolecular films on silicon substrates. Construction of hybrid carbon-silicon devices in which molecular organic molecular films are covalently linked to silicon wafers. Biomolecular nanostructures on silicon wafers can be studied using unique impedance spectroscopy instrumentation that we have developed as well as X-ray and neutron reflectometry. The system will be used to study a variety of molecular films as well as molecularly tethered lipid bilayer membranes that mimic aspects of cell membranes and these will be used to investigate the effect of sterols on such membranes.Read moreRead less
Intracellular calcium in intact muscle during fatigue and stretch-induced damage. Confocal microscopes can investigate intact tissues during normal function. We will develop and apply this novel approach to muscle. We expect this new approach to become a fundamental new tool for exploring muscle function under near normal conditions. Muscle pain and weakness are common disabilities in humans and we expect this new approach to provide insights into the causes and treatment of these common cond ....Intracellular calcium in intact muscle during fatigue and stretch-induced damage. Confocal microscopes can investigate intact tissues during normal function. We will develop and apply this novel approach to muscle. We expect this new approach to become a fundamental new tool for exploring muscle function under near normal conditions. Muscle pain and weakness are common disabilities in humans and we expect this new approach to provide insights into the causes and treatment of these common conditions.Read moreRead less
Quantitative Brain Dynamics. This proposal will benefit Australia through unique and fundamental contributions to understanding brain dynamics via the development of innovative approaches and technologies. It will contribute to the national priority goals of Breakthrough Science, Frontier Technologies, and Promoting an Innovation Culture and Economy. Science outcomes will include improved understanding and probing of brain self-organization, dynamics, and function, including unique contributio ....Quantitative Brain Dynamics. This proposal will benefit Australia through unique and fundamental contributions to understanding brain dynamics via the development of innovative approaches and technologies. It will contribute to the national priority goals of Breakthrough Science, Frontier Technologies, and Promoting an Innovation Culture and Economy. Science outcomes will include improved understanding and probing of brain self-organization, dynamics, and function, including unique contributions to understanding alertness and the foundations of vision. These outcomes will be applied to develop new technologies for brain imaging and monitoring.Read moreRead less
Microfluidic device for microbial separation and concentration. This project will enhance Australia's capabilities and presence in the rapidly expanding field of chemical and biological analysis systems on a chip. We will develop and build handheld devices for microbial concentration that will facilitate earlier and easier detection of potentially pathogenic organisms in critical situations such as epidemiological crises or forensics. The portability and ease of operation of our integrated micro ....Microfluidic device for microbial separation and concentration. This project will enhance Australia's capabilities and presence in the rapidly expanding field of chemical and biological analysis systems on a chip. We will develop and build handheld devices for microbial concentration that will facilitate earlier and easier detection of potentially pathogenic organisms in critical situations such as epidemiological crises or forensics. The portability and ease of operation of our integrated microfluidic devices and their increased resilience to blockages make them ideal for use in remote areas and non-laboratory settings. Application areas will include disease detection, microbial contamination in food industries and water quality monitoring.Read moreRead less
Resurgent Sodium Currents in Peripheral Nerve Axons and Sensory Neurones. This project seeks evidence that unusual gating of sodium channels contributes to the hyperexcitability that results in spontaneous impulse activity in sensory axons. It asks whether axons normally behave as if they have this gating mode, whether it can be induced, whether any such behaviour is more prominent with sensory axons than motor, and whether the current can be measured directly in sensory neurones. The project is ....Resurgent Sodium Currents in Peripheral Nerve Axons and Sensory Neurones. This project seeks evidence that unusual gating of sodium channels contributes to the hyperexcitability that results in spontaneous impulse activity in sensory axons. It asks whether axons normally behave as if they have this gating mode, whether it can be induced, whether any such behaviour is more prominent with sensory axons than motor, and whether the current can be measured directly in sensory neurones. The project is the first to involve correlation of patch-clamp recordings with the behaviour of intact axons. Its outcomes will affect thought about sodium channel behaviour and may alter approaches to disorders of axonal excitability.Read moreRead less
Characterisation of the CLIC1 chloride ion channel by a novel biophysical method: Site-Directed-Spin-Labeling Electron Paramagnetic Resonance Spectroscopy. Chloride ion channels are involved in diverse physiological processes and channel malfunction can lead to severe diseases. This project examines the structure and conformational changes of a member of the newly described chloride channel family (CLIC1) using an emerging biophysical technique. CLIC1 is unique due to its ability to transit be ....Characterisation of the CLIC1 chloride ion channel by a novel biophysical method: Site-Directed-Spin-Labeling Electron Paramagnetic Resonance Spectroscopy. Chloride ion channels are involved in diverse physiological processes and channel malfunction can lead to severe diseases. This project examines the structure and conformational changes of a member of the newly described chloride channel family (CLIC1) using an emerging biophysical technique. CLIC1 is unique due to its ability to transit between soluble and active membrane channel forms. Our novel approach to determine the channel structure represents a major advance in overcoming numerous difficulties associated with traditional atomic resolution structural-biology techniques. This proposal also opens up new experimental avenues to understand biological important events associated with ion channels, including channel gating.Read moreRead less
Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional character ....Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional characterisation of this class of potassium channels is of great importance as they are interesting targets for new therapeutic developments. Advancement of knowledge in the structure and function of these channels will underpin drug targeting that will aid preventative healthcare, allowing Australians to age well and age productively.Read moreRead less