Molecular basis of G protein receptor-effector coupling in epithelial cells. Hundreds of extracellular stimuli act on specific receptors in the plasma membrane of cells resulting in an increase in intracellular calcium which acts as a second messenger to alter cell behaviour. There are, however, many receptors acting through a number of closely related proteins involving tightly regulated interactions which remain poorly understood. This project uses novel techniques to elucidate the molecular b ....Molecular basis of G protein receptor-effector coupling in epithelial cells. Hundreds of extracellular stimuli act on specific receptors in the plasma membrane of cells resulting in an increase in intracellular calcium which acts as a second messenger to alter cell behaviour. There are, however, many receptors acting through a number of closely related proteins involving tightly regulated interactions which remain poorly understood. This project uses novel techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in this complex process.Read moreRead less
Fundamental theoretical and experimental investigation of cartilage mechanics. Arthritis and chronic joint symptoms are one of the leading causes of disability in the community, yet a fundamental understanding of joint mechanics has yet to be realised. The aim of this project is to develop a new state-of-the-art mathematical model describing cartilage behaviour in humans. The model will explain how activities like walking maintain healthy cartilage by transferring growth factors through the tiss ....Fundamental theoretical and experimental investigation of cartilage mechanics. Arthritis and chronic joint symptoms are one of the leading causes of disability in the community, yet a fundamental understanding of joint mechanics has yet to be realised. The aim of this project is to develop a new state-of-the-art mathematical model describing cartilage behaviour in humans. The model will explain how activities like walking maintain healthy cartilage by transferring growth factors through the tissue, and quantitatively explain how wear is minimised in cartilage through weeping lubrication. This model will progress our understanding of cartilage mechanics in health and disease, and so help Australians age well and productively.Read moreRead less
Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. ....Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. 2)Enhancement of Australia's reputation in gastrointestinal (GI) research through a unique collaboration between internationally recognised researchers in GI and pancreatic biology. 3)Training opportunities for Australian research students and scientists in physiology, gastroenterology and pancreatology.Read moreRead less
Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occul ....Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occult segmental pattern in adult mice. This work will give us a new way of understanding the organisation of brainstem centres that control breathing, cardiovascular functions and emotional states.Read moreRead less
INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generat ....INVESTIGATION OF A BRAIN RHYTHM. Elucidation of brain function remains a frontier for human discovery. To date, research has largely focussed on brain connectivity with major advances in knowledge of input/output function of brain regions. Yet, there remains little understanding of higher order processes that underlie functions such as mood states and consciousness. Investigation of brain rhythms represent a step to unravelling such processes, as rhythms both act as autonomous clocks and generate synchronised neuronal activity. This project aims to investigate mechanisms underlying a specific class of brain rhythm implicated in control of mood states. Positive outcomes from this basic research may lead to better drug therapies for controlling specific mental disorders.Read moreRead less
Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
Central command neurons integrating cardiorespiratory drive in exercise. The ability to perform exercise is fundamental to human health and welfare. This ability depends upon the co-ordination by the brain of respiratory and cardiovascular function, such that the delivery of oxygen to exercising muscles is maximised. This project will test the idea that there is a specific group of neurons in the brain that drive both the respiratory and cardiovascular changes that occur during exercise, and w ....Central command neurons integrating cardiorespiratory drive in exercise. The ability to perform exercise is fundamental to human health and welfare. This ability depends upon the co-ordination by the brain of respiratory and cardiovascular function, such that the delivery of oxygen to exercising muscles is maximised. This project will test the idea that there is a specific group of neurons in the brain that drive both the respiratory and cardiovascular changes that occur during exercise, and will determine the location and functions of such neurons. Such new knowledge will help us understand how the brain optimises the ability of the body to perform exercise. This is of fundamental importance in sports science, a field in which Australia excels.Read moreRead less
The implications of resistance training for the control of movement. Resistance training (or weight lifting) is an essential element of comprehensive rehabilitation programs in a wide range of clinical settings. However, because we know little about how the organization of the nervous system is affected by training with high loads, the consequences of resistance training for our ability to control functional movements are unclear. The ultimate goal of this research is to generate basic knowledge ....The implications of resistance training for the control of movement. Resistance training (or weight lifting) is an essential element of comprehensive rehabilitation programs in a wide range of clinical settings. However, because we know little about how the organization of the nervous system is affected by training with high loads, the consequences of resistance training for our ability to control functional movements are unclear. The ultimate goal of this research is to generate basic knowledge about the impact of resistance training on nervous system function. The research will lead to the design of injury prevention and rehabilitation programs that are maximally effective, and provide a genuine benefit to the community.Read moreRead less
Microglia and the inflammation spectrum - not just good or bad. Cell-mediated tissue clearance following brain injury is a universal mechanism. However, our understanding of the cells that perform these tasks is very limited. Our project will characterise this inflammatory response at a single-cell level using the zebrafish spinal cord as a versatile experimental model. The project is expected to strongly contribute to the molecular understanding of the mechanisms underlying debris removal and w ....Microglia and the inflammation spectrum - not just good or bad. Cell-mediated tissue clearance following brain injury is a universal mechanism. However, our understanding of the cells that perform these tasks is very limited. Our project will characterise this inflammatory response at a single-cell level using the zebrafish spinal cord as a versatile experimental model. The project is expected to strongly contribute to the molecular understanding of the mechanisms underlying debris removal and will advance innovative technologies that facilitate intellectual progress in neuroscience. It will produce new insights into the process of neuronal degeneration, promote Australia’s growing reputation as a global leader in neuroscience, and provide high quality training for early career researchers.Read moreRead less
Calcium Signalling and Sequestration at Vertebrate Motor-Nerve Terminals. A fundamental process at Synapses is the release of transmitter from nerve terminals due to the initiation of calcium signalling in the temrinals by impulses. This calcium signalling must be terminated by sequestering processes. The aim of this project is to identify these processes in a vertebrate motor-nerve terminal and to determine the means by which calcium signals the changes in efficacy of transmitter release during ....Calcium Signalling and Sequestration at Vertebrate Motor-Nerve Terminals. A fundamental process at Synapses is the release of transmitter from nerve terminals due to the initiation of calcium signalling in the temrinals by impulses. This calcium signalling must be terminated by sequestering processes. The aim of this project is to identify these processes in a vertebrate motor-nerve terminal and to determine the means by which calcium signals the changes in efficacy of transmitter release during trains of impulses. This work will give a complete description of calcium signalling in a vertebrate nerve terminal and provide the basis for ameliorating failures in transmission from nerve to muscle.Read moreRead less