Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously ....Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously, whilst recording intestinal muscle electrical activity and the movements of the gut wall, the project expects to identify which enteric neurochemical classes of neurons generate specific motor patterns along the intestine.Read moreRead less
Mapping sites of visceral convergence connecting the colon and bladder. This project aims to develop multiple neuroanatomical approaches to identify where in the central nervous system the sensory signalling from the colon and bladder merge. The combination of such technologies is novel to the study of the central circuits relaying colon/bladder convergence into the brain and will generate new and detailed knowledge of the central pathways in which pelvic organ sensory (discomfort) and motor (de ....Mapping sites of visceral convergence connecting the colon and bladder. This project aims to develop multiple neuroanatomical approaches to identify where in the central nervous system the sensory signalling from the colon and bladder merge. The combination of such technologies is novel to the study of the central circuits relaying colon/bladder convergence into the brain and will generate new and detailed knowledge of the central pathways in which pelvic organ sensory (discomfort) and motor (defecation/urination) functions are coordinated. The expected outcomes are predicted to aid future discovery of mechanisms of cross-organ sensitisation and are anticipated to provide significant benefit to therapy development for chronic visceral pain syndromes associated with bowel and bladder dysfunction.Read moreRead less
How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less
Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods ....Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods to simplify the analysis of multimodal path-clamping data (Patch-seq). Expected outcomes will facilitate research collaboration and the reproducibility of accurate experimental replicates of the human brain. This will provide significant benefits in the global race to understand human brain computation mechanisms.Read moreRead less
How Spinal Afferent Neurons Control Appetite and Thirst . This project aims to provide major new insights about how the gut communicates with the brain, to regulate how much food and fluids have been consumed. The proposal expects to generate new knowledge about gut-brain communication and how one of the major sensory nerves from the gut relays information about thirst and appetite sensations. The project addresses fundamental questions that rely on techniques only recently developed in our labo ....How Spinal Afferent Neurons Control Appetite and Thirst . This project aims to provide major new insights about how the gut communicates with the brain, to regulate how much food and fluids have been consumed. The proposal expects to generate new knowledge about gut-brain communication and how one of the major sensory nerves from the gut relays information about thirst and appetite sensations. The project addresses fundamental questions that rely on techniques only recently developed in our laboratory. We expect to demonstrate a major new sensory nerve pathway from the gut to the brain that plays a major role in appetite and thirst sensations. We will learn how gut to brain communication underlies the feeling of "fullness" when people consume food and drink.
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How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innov ....Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innovative genome editing, mathematical modelling and proteomic approaches, to study how biochemical modifications of a key protein called tau help encode and retrieve memories. These molecular insights will make a significant advance in the current understanding of a brain function that is essential to all human activities.Read moreRead less
Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, wh ....Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, which is an essential component of human and animal life. This research provides significant benefits in understanding the biology behind memory and in maintaining memory capacity in ageing.
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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
Engineered plant receptors as orthogonal neuronal switches. This project aims to develop synthetic biology methods to study brain function by utilising engineered plant receptors. This project will expand our ability to manipulate nerve cell function with high specificity and without side effects in freely behaving animals. Plant receptors will be developed into molecular tools in an iterative process that improves key properties using rational protein design. Expected outcomes include innovativ ....Engineered plant receptors as orthogonal neuronal switches. This project aims to develop synthetic biology methods to study brain function by utilising engineered plant receptors. This project will expand our ability to manipulate nerve cell function with high specificity and without side effects in freely behaving animals. Plant receptors will be developed into molecular tools in an iterative process that improves key properties using rational protein design. Expected outcomes include innovative and broadly-applicable neuroscience methods and an understanding of receptors involved in plant growth and defense. Benefits of this project include an enhanced capacity to generate knowledge, multidisciplinary training opportunities and patentable synthetic biology technologies.Read moreRead less