Cellular mechanisms that protect against copper-bound beta-amyloid. This project will investigate some of the brain’s own mechanisms for protecting itself against Alzheimer’s disease. Understanding these mechanisms will be important for developing future therapeutic strategies for treating Alzheimer’s disease.
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
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
Novel role of RNA methylation in neuronal homeostasis. This proposal is aimed at understanding the RNA signalling that takes place in neuronal homeostatic response. The crucial role of neuronal homeostasis for normal brain function is evidenced throughout the nervous system; however, the precise underlying mechanisms are still not well understood. The proposed research will utilise high-throughput sequencing approaches coupled with biochemical, molecular and cell biological assays to provide mec ....Novel role of RNA methylation in neuronal homeostasis. This proposal is aimed at understanding the RNA signalling that takes place in neuronal homeostatic response. The crucial role of neuronal homeostasis for normal brain function is evidenced throughout the nervous system; however, the precise underlying mechanisms are still not well understood. The proposed research will utilise high-throughput sequencing approaches coupled with biochemical, molecular and cell biological assays to provide mechanistic insights into the molecular processes that control neuronal homeostatic responses. This will elucidate how neural plasticity and network stability are maintained, a process that is critical for our understanding of sensory processing, learning and memory throughout life.Read moreRead less
Mechanism of transmission of calcium waves by glial cells. This research concerns determining the fundamental properties of cells that occupy about 70% of the brain, the glial cells. Two very important discoveries on glial cells have recently been made, namely that they can convey information in the form of patterns of waves and that they possess molecules on their surface membranes that have been implicated in psychotic disorders. One such molecule is called the D2 receptor and its malfunctioni ....Mechanism of transmission of calcium waves by glial cells. This research concerns determining the fundamental properties of cells that occupy about 70% of the brain, the glial cells. Two very important discoveries on glial cells have recently been made, namely that they can convey information in the form of patterns of waves and that they possess molecules on their surface membranes that have been implicated in psychotic disorders. One such molecule is called the D2 receptor and its malfunctioning has been implicated in schizophrenia. Our research will determine the way in which information is propagated in the glial system of the brain and also illuminate the function of several of the molecules found on the surface of the glial cells.Read moreRead less
Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem ....Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem cell-derived mechanosensory neurons as a platform to extensively study their molecular and functional properties. The significant benefits are the advancement of knowledge in the human mechanosensory system, which to date has been lacking, and in the long-term progress commercial development of novel drugs.Read moreRead less
Neuron-microglia signalling mechanisms. This research concerns determining the fundamental mechanisms by which one of the principal non-neuronal cells in the brain , the microglial cell, interacts with neurons to change their properties. The correct functioning of neural networks is necessary for our normal behaviour. Such networks can be disrupted and indeed destroyed by the release of inflammatory molecules from microglial cells. In this work the way in which anti-inflammatory molecules are re ....Neuron-microglia signalling mechanisms. This research concerns determining the fundamental mechanisms by which one of the principal non-neuronal cells in the brain , the microglial cell, interacts with neurons to change their properties. The correct functioning of neural networks is necessary for our normal behaviour. Such networks can be disrupted and indeed destroyed by the release of inflammatory molecules from microglial cells. In this work the way in which anti-inflammatory molecules are released from the microglia will be elucidated, thus providing insight into how to prevent the destructive actions of the inflammatory molecules on the nervous system. Read moreRead less
Beyond Neuroinflammation: The Role of Microglia in Synaptic Plasticity. Microglia are the immune cells of the brain and are known to respond to infectious and non-infectious insults to the nervous system. This project aims to use the transparent and genetically amenable brain of the zebrafish, to explore new functions of microglia at the single cell level in the intact, behaving animal, through visualization of cellular components of the brain (neurons, glia, microglia, blood vessels, synapses), ....Beyond Neuroinflammation: The Role of Microglia in Synaptic Plasticity. Microglia are the immune cells of the brain and are known to respond to infectious and non-infectious insults to the nervous system. This project aims to use the transparent and genetically amenable brain of the zebrafish, to explore new functions of microglia at the single cell level in the intact, behaving animal, through visualization of cellular components of the brain (neurons, glia, microglia, blood vessels, synapses), and through the genetic manipulation of synaptic density, and real time observation of microglia in the process.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