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
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
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
Listen and learn - statistical learning and the adapting auditory brain. This project aims to explore the link between rapid neural adaptation - a form of learning referred to as statistical learning - and human listening performance in noisy environments. The project aims to generate a new understanding of mechanisms that contribute to listeners' abilities to understand speech in noise, and to complex communication disorders such as dyslexia. Expected outcomes will include increased capacity to ....Listen and learn - statistical learning and the adapting auditory brain. This project aims to explore the link between rapid neural adaptation - a form of learning referred to as statistical learning - and human listening performance in noisy environments. The project aims to generate a new understanding of mechanisms that contribute to listeners' abilities to understand speech in noise, and to complex communication disorders such as dyslexia. Expected outcomes will include increased capacity to investigate a broad range of cognitive and communication functions. Benefits will include potential technologies and algorithms to assist listening (in devices such as hearing aids), language development and reading.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
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
The role of LIM Kinase 1 in neurons. The aim of this project is to study LIM domain kinase 1 in neuronal function, using cell and mouse models. Unrestricted brain function is essential to one’s wellbeing and the ability to perform normally. Critically contributing to the function of neurons is a cytoskeleton which maintains morphology and function. However, molecular mechanisms underlying cytoskeletal dynamics are poorly understood. LIM domain kinase 1, a key regulator of the actin cytoskeleton ....The role of LIM Kinase 1 in neurons. The aim of this project is to study LIM domain kinase 1 in neuronal function, using cell and mouse models. Unrestricted brain function is essential to one’s wellbeing and the ability to perform normally. Critically contributing to the function of neurons is a cytoskeleton which maintains morphology and function. However, molecular mechanisms underlying cytoskeletal dynamics are poorly understood. LIM domain kinase 1, a key regulator of the actin cytoskeleton decreased with age and its loss associated with deficits in memory and neuronal morphology. This project could reveal fundamental processes regulating and maintaining brain function.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