A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of the ....A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of their ion channels (selective protein pores) and receptors contribute to the odorant-induced generation of electrical activity, which mediates our sense of smell (olfaction). The project has specific relevance for understanding olfaction, as well as relevance for other sensory systems and other ion channels.Read moreRead less
SKELETAL MUSCLE: REVERSIBLE TEMEPERATURE-INDUCED UNCOUPLING OF CONTRACTION FROM THE ACTIVATOR Ca2+ AND TUBULAR SYSTEM ROLES IN MUSCLE FUNCTION REGULATION. Skeletal muscles represent the largest organ in the body of vertebrates and are responsible for major functions including maintaining posture and locomotion. Skeletal muscles are also a major source of heat production. The project focuses on temperature-induced effects on the ability of the skeletal muscle to contract in warm blooded animals, ....SKELETAL MUSCLE: REVERSIBLE TEMEPERATURE-INDUCED UNCOUPLING OF CONTRACTION FROM THE ACTIVATOR Ca2+ AND TUBULAR SYSTEM ROLES IN MUSCLE FUNCTION REGULATION. Skeletal muscles represent the largest organ in the body of vertebrates and are responsible for major functions including maintaining posture and locomotion. Skeletal muscles are also a major source of heat production. The project focuses on temperature-induced effects on the ability of the skeletal muscle to contract in warm blooded animals, including marsupials, and on the complex roles played by a cellular structure unique to the muscle fibre, the tubular system, with respect to regulation of muscle function at physiological temperatures. The project will test hypotheses that will have far-reaching implications for muscle physiology, cell biology and evolutionary biology.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
Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothe ....Aquaporin channels in cell migration. The project aims to determine the role of Aquaporin1 (AQP1) in enhancing rapid cell motility. Cell migration is important for development, repair, and protection in multicellular organisms. AQP1 is increased in some rapidly migrating cell types. Loss of AQP1 impairs migration, which is restored by reintroduction of AQP1 but not AQP4. Expected outcomes include defining the features of AQP1 that confer enhanced cell migration. The project will test the hypothesis that dual water and ion channel functions of AQP1 are needed for movement, using migration assays in cells with wild type and mutant AQP1, and selective pharmacological agents developed by the project team to dissect the essential channel properties that enable rapid migration in cancer and stem cells. The project seeks to build knowledge of AQP roles in development, regeneration and surveillance, potentially improving health care by revealing pathways in migration disorders such as metastasis.Read moreRead less
Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers i ....Fundamental roles of aquaporin-1 channels in cell migration and morphology. This project aims to investigate cell migration mechanisms and the roles of aquaporin channels in controlling cell motility and morphology. The ability of cells to move and maintain proper shape is important for development, repair and survival in multicellular organisms. This project will test the role of mammalian aquaporin-1 channels in enabling rapid migration in normal and cancer cells, in repairing barrier layers in kidney and brain, and in allowing red blood cells to maintain the classic disk-shape needed for optimal transport. Outcomes will define features of aquaporin-1 that provide these functions, using molecular, optical and pharmacological tools. Results will define aquaporin channel properties that enable optimal cellular function.Read moreRead less
Cardiac a1-adrenergic receptors in survival of the fittest. This project aims to determine the role of alpha1A-adrenergic receptor inactivation, a receptor/signalling pathway, in mediating cardiac contraction and survival in response to stressors fight-or-flight response triggers.Higher organisms’ ability to respond to environmental changes is central to the survival of the fittest, and is mediated by the release of catecholamines that stimulate adrenergic receptors. The precise receptor and sig ....Cardiac a1-adrenergic receptors in survival of the fittest. This project aims to determine the role of alpha1A-adrenergic receptor inactivation, a receptor/signalling pathway, in mediating cardiac contraction and survival in response to stressors fight-or-flight response triggers.Higher organisms’ ability to respond to environmental changes is central to the survival of the fittest, and is mediated by the release of catecholamines that stimulate adrenergic receptors. The precise receptor and signalling pathways underlying these adaptive responses remain unclear. This project’s research could improve contractility, reduce cardiomyocyte death and define organismal adaptation to extreme environmental changes.Read moreRead less
Nutritional and bacterial influences on gut and peripheral homeostasis. Nutritional and bacterial influences on gut and peripheral homeostasis. This project aims to understand the role of macronutrients on gut homeostasis. While the understanding of what factors affect gut homeostasis is still in its infancy, scientists know that its disruption contributes to a broad range of inflammatory diseases, including type 1 diabetes and asthma. This project will determine the role of specific macronutrie ....Nutritional and bacterial influences on gut and peripheral homeostasis. Nutritional and bacterial influences on gut and peripheral homeostasis. This project aims to understand the role of macronutrients on gut homeostasis. While the understanding of what factors affect gut homeostasis is still in its infancy, scientists know that its disruption contributes to a broad range of inflammatory diseases, including type 1 diabetes and asthma. This project will determine the role of specific macronutrients on gut microbiota, gut epithelium, and immunity in mice, and the receptors involved. This research could ultimately lead to significant decreases in the cost of healthcare.Read moreRead less
Amino acids as nutrients - the molecular basis of amino acid absorption in kidney and intestine. Nutrition is a critical factor for well being and health. This is highlighted by the increase in frequency of type II diabetes and the obesity problem that all societies with a western diet face. Most studies in nutrition focus on fat and carbohydrates because of their direct involvement in obesity and diabetes. Proteins and the resulting peptides and amino acids, however, form 10-15% of our nutritio ....Amino acids as nutrients - the molecular basis of amino acid absorption in kidney and intestine. Nutrition is a critical factor for well being and health. This is highlighted by the increase in frequency of type II diabetes and the obesity problem that all societies with a western diet face. Most studies in nutrition focus on fat and carbohydrates because of their direct involvement in obesity and diabetes. Proteins and the resulting peptides and amino acids, however, form 10-15% of our nutrition. At a time where protein-rich diets are recommended to fight obesity and diabetes, it is important to understand the basis of protein absorption and metabolism. This project investigates the mechanism and mediators of amino acid absorption in kidney and intestine. Read moreRead less
Novel anti-ageing peptides in the vascular system. The project will substantially improve basic understanding of the ageing process in blood vessels and provide scientific evidence to understand what preventative health care measures might work and why. It will also produce highly skilled and practically trained graduates, ready to contribute to the health industry.
How triadin and junctin communicate with ryanodine receptors deep within a calcium store to determine skeletal muscle contraction. The project results will provide a platform for muscle relaxants and other drugs that will specifically target either the heart or skeletal muscle and will have applications in the livestock, veterinary and pharmaceutical Industries. The project falls within the National Research Priorities of Promoting and Maintaining Good Health and Frontier Technologies for Buil ....How triadin and junctin communicate with ryanodine receptors deep within a calcium store to determine skeletal muscle contraction. The project results will provide a platform for muscle relaxants and other drugs that will specifically target either the heart or skeletal muscle and will have applications in the livestock, veterinary and pharmaceutical Industries. The project falls within the National Research Priorities of Promoting and Maintaining Good Health and Frontier Technologies for Building and Transforming Australian Industries, as well as the national priority goal of Ageing well, Ageing Productively. The project will be of national benefit in training undergraduate students, PhD students and a postdoctoral fellow in state-of-the-art techniques in an internationally competitive research field.Read moreRead less