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
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
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
Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechan ....Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechanisms by which these compounds act. By discovering their site and mechanisms of action we will further our understanding of these important proteins and their modulation, maintain Australia's significant expertise in this field and provide leads for future development of drugs with potential therapeutic value.Read moreRead less
Molecular force sensing mechanisms of PIEZO channels. The aim of this project is to characterise the gating mechanism of Piezo mechanosensitive ion channels recently identified in animals and humans. Mechanotransduction is ancient, as indicated by the presence of mechanosensitive channels in bacteria where these channels are activated by the bilayer mechanism according to the force-from-lipids paradigm possibly applicable to gating of the Piezo channels as well. Piezo channels play a crucial rol ....Molecular force sensing mechanisms of PIEZO channels. The aim of this project is to characterise the gating mechanism of Piezo mechanosensitive ion channels recently identified in animals and humans. Mechanotransduction is ancient, as indicated by the presence of mechanosensitive channels in bacteria where these channels are activated by the bilayer mechanism according to the force-from-lipids paradigm possibly applicable to gating of the Piezo channels as well. Piezo channels play a crucial role in senses of touch and pain, and mutations in Piezo1 have been shown to cause Xerocytosis – a hereditary genetic disorder manifested in haemolytic anemia. This project aims to help answer fundamental questions in mechanotransduction in vertebrates.Read moreRead less
A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To un ....A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To understand how the method can be optimized, the thermodynamic pathway of membrane disruption will be investigated at a single cell level. The methods and insights arising from this project could eventually lead to novel, patentable and lower-cost health technologies.Read moreRead less