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
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
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
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
Organic Bioelectronics: Solving Key Barriers to Precision Neuromodulation. This project aims to combine the principles of molecular electronics and neurobiology to create organic conductors with enhanced biocompatibility that enable optical neuromodulation. This project expects to generate new knowledge regarding the properties of materials that promote connectivity with neurons and the ability of new microscopy tools to visualise this bio-interface. The expected outcome of this project includes ....Organic Bioelectronics: Solving Key Barriers to Precision Neuromodulation. This project aims to combine the principles of molecular electronics and neurobiology to create organic conductors with enhanced biocompatibility that enable optical neuromodulation. This project expects to generate new knowledge regarding the properties of materials that promote connectivity with neurons and the ability of new microscopy tools to visualise this bio-interface. The expected outcome of this project includes new high performing materials, measurement tools and fabrication approaches to overcome the key challenges to precision neuromodulation. A significant benefit of the new materials is their printability, providing the opportunity to establish a sovereign capability to manufacture low-cost bioelectronic systems in Australia.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
Spatiotemporal signatures of learning in brain reward systems. Learning to strengthen behaviours that secure resources and warrant survival is one of the primary functions of the brain. This Project seeks to establish the rules that govern the integration of learning in brain reward systems by studying how neuronal circuits change their molecular signatures as animals assimilate new knowledge. These studies will combine novel experimental designs to investigate learning with multidisciplinary me ....Spatiotemporal signatures of learning in brain reward systems. Learning to strengthen behaviours that secure resources and warrant survival is one of the primary functions of the brain. This Project seeks to establish the rules that govern the integration of learning in brain reward systems by studying how neuronal circuits change their molecular signatures as animals assimilate new knowledge. These studies will combine novel experimental designs to investigate learning with multidisciplinary methods for mapping, recording and functionalising teaching signals in behaving mice. The outcomes will create a significant shift in our understanding of the neural bases that underlie reward learning, and will critically expand the field by providing a new model of learning integration in brain systems.Read moreRead less
Mechanisms of memory integration in brain systems. Learning from our interactions with the environment is one of the brain’s most important functions, yet how and where this process takes place at the neural network level has proven difficult to establish. This Project seeks to investigate how major neuromodulatory signals in the brain coordinate the encoding of reward-based learning in large ensembles of neurons. These studies will combine novel behavioural paradigms with the most recent neuros ....Mechanisms of memory integration in brain systems. Learning from our interactions with the environment is one of the brain’s most important functions, yet how and where this process takes place at the neural network level has proven difficult to establish. This Project seeks to investigate how major neuromodulatory signals in the brain coordinate the encoding of reward-based learning in large ensembles of neurons. These studies will combine novel behavioural paradigms with the most recent neuroscience techniques for functional mapping and manipulation of specific neural circuits in behaving mice. The outcomes of this research will lead to a significant shift in our understanding of the mechanisms underpinning the integration of learning in brain systems and its implications for behaviour.Read moreRead less
How satiation control reward value and cue-induced appetitive behaviours. This proposal aims to identify mechanisms that control environment-driven food-seeking behaviours. It seeks to do so by using modern virally-mediated and basic behavioural as well as histological techniques in a transgenic rat to characterise novel hindbrain circuits that control these feeding behaviours. This is significant as environment-driven overeating is problematic yet underlying mechanisms are unclear. This project ....How satiation control reward value and cue-induced appetitive behaviours. This proposal aims to identify mechanisms that control environment-driven food-seeking behaviours. It seeks to do so by using modern virally-mediated and basic behavioural as well as histological techniques in a transgenic rat to characterise novel hindbrain circuits that control these feeding behaviours. This is significant as environment-driven overeating is problematic yet underlying mechanisms are unclear. This project expects to provide new knowledge on when, where and how hindbrain neurons control environment-driven food-seeking behaviours. This should provide benefits to the advancement of knowledge on the neural mechanisms of food-seeking and provide a basic science platform for future research on the study of feeding behaviours.
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Hippocampal regulation of goal-directed decision-making. The hippocampus is a part of the brain that is central to learning and memory yet little is known about its role in decision-making. It is the aim of this application to provide the first detailed, causal evidence of hippocampal regulation of decision-making. This is significant because many mental health disorders and dementias that involve decision-making deficits are characterised by hippocampal dysfunction, but any direct link between ....Hippocampal regulation of goal-directed decision-making. The hippocampus is a part of the brain that is central to learning and memory yet little is known about its role in decision-making. It is the aim of this application to provide the first detailed, causal evidence of hippocampal regulation of decision-making. This is significant because many mental health disorders and dementias that involve decision-making deficits are characterised by hippocampal dysfunction, but any direct link between these factors is unknown. The outcomes of the current grant will provide the first evidence of that link, thus providing deeper understanding of the neurophysiological mechanisms of these disorders, which could eventuate in the creation of more beneficial treatments. Read moreRead less