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
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
Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and r ....Brain metabolic changes in experimental malaria: a paradigm for the molecular mechanisms of intravascular inflammation. Malaria is endemic in countries directly to the north of Australia, as close as Papua New Guinea and East Timor. This project's findings about malaria also will have relevance to other infectious diseases of national importance. The outcomes will contribute to Australia's research reputation. We will build international links that will increase the national knowledge base and research skill base. Young scientists will be trained in state-of-the-art research techniques in a cross-disciplinary environment that is the way of future biological research. The project may identify potential drug targets for malaria or other infectious diseases. The Intellectual Property will be protected and commercialised.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
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
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
Exploring the brain mechanisms underlying hyperactivity in Attention-Deficit/Hyperactivity Disorder. Attention-deficit/Hyperactivity Disorder (AD/HD) is the most common psychiatric disorder affecting children, resulting in substantial costs (both human and financial) to the child, their family and Australian society. The outcomes of this project will provide a better foundation for understanding dysfunctional brain mechanisms in AD/HD, which is expected to lead to better diagnosis, treatment, an ....Exploring the brain mechanisms underlying hyperactivity in Attention-Deficit/Hyperactivity Disorder. Attention-deficit/Hyperactivity Disorder (AD/HD) is the most common psychiatric disorder affecting children, resulting in substantial costs (both human and financial) to the child, their family and Australian society. The outcomes of this project will provide a better foundation for understanding dysfunctional brain mechanisms in AD/HD, which is expected to lead to better diagnosis, treatment, and community support. Ultimately this will contribute to a healthy start to life for these children. This project will also demonstrate how an integrated Australian approach can lead the research agenda in both basic neuroscience, at the interface of psychology and physiology, and its applications in health.Read moreRead less
Adaptation of respiratory chemoreception: role of inhibitory neuropeptides. The project aims to investigate how the retrotrapezoid nucleus (RTN) is involved in respiratory adaptation to hypercapnia. Chemoreceptor neurons in the RTN are crucial for life however, the mechanisms that underlie their basal and stimulated activity, to control breathing, remain to be clarified. This project will investigate the role of galanin in RTN-mediated regulation of breathing. The project looks to determine inst ....Adaptation of respiratory chemoreception: role of inhibitory neuropeptides. The project aims to investigate how the retrotrapezoid nucleus (RTN) is involved in respiratory adaptation to hypercapnia. Chemoreceptor neurons in the RTN are crucial for life however, the mechanisms that underlie their basal and stimulated activity, to control breathing, remain to be clarified. This project will investigate the role of galanin in RTN-mediated regulation of breathing. The project looks to determine instructive and multifunctional roles of peptidergic chemosensory neurons and their contribution to local inhibitory control of the respiratory network. New knowledge from the project may in the future assist translational research into respiratory disorders and lead to technological advances.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