Plasticity of gastrointestinal vagal afferents. The aim of this project is to identify how leptin modulates specific subtypes of vagal afferent within the gut and the plasticity of this system under different dietary conditions. This proposed project will substantially increase understanding of the interactions between leptin, known to influence food intake, and vagal afferent satiety signals. It will also increase understanding of how these interactions alter in obesity and ultimately provide t ....Plasticity of gastrointestinal vagal afferents. The aim of this project is to identify how leptin modulates specific subtypes of vagal afferent within the gut and the plasticity of this system under different dietary conditions. This proposed project will substantially increase understanding of the interactions between leptin, known to influence food intake, and vagal afferent satiety signals. It will also increase understanding of how these interactions alter in obesity and ultimately provide targets and/or concepts for the pharmacotherapy of obesity.Read moreRead less
A more sound approach to the neurobiology of language. How does the brain attain spoken language? Current neurobiological models assume either implicitly or explicitly that there is no relationship between a word's sound and its meaning. Yet considerable evidence shows this strong assumption about the arbitrariness of language is invalid. This project will use a combination of behavioural, neuroimaging and computational studies to characterise how the brain processes statistical regularities in ....A more sound approach to the neurobiology of language. How does the brain attain spoken language? Current neurobiological models assume either implicitly or explicitly that there is no relationship between a word's sound and its meaning. Yet considerable evidence shows this strong assumption about the arbitrariness of language is invalid. This project will use a combination of behavioural, neuroimaging and computational studies to characterise how the brain processes statistical regularities in sound-to-meaning correspondences as probabilistic cues to attain spoken language. The outcome will be a better neural account of language comprehension and production. The benefit of this new account will be a stronger basis for assessment and treatment of developmental and acquired language impairments.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
Investigating differences in decision-making ability in older adults. This project aims to investigate how healthy ageing impacts decision making and its associated neural circuits using computation modelling and neurogenetic methods. Decision-making is a fundamental cognitive ability, allowing us to choose the best course of action. This project will investigate the relationship between genes and decision-making performance across the adult lifespan. Expected outcomes include a deeper understan ....Investigating differences in decision-making ability in older adults. This project aims to investigate how healthy ageing impacts decision making and its associated neural circuits using computation modelling and neurogenetic methods. Decision-making is a fundamental cognitive ability, allowing us to choose the best course of action. This project will investigate the relationship between genes and decision-making performance across the adult lifespan. Expected outcomes include a deeper understanding of how decision-making evolves in healthy ageing, and a tool based on genetic scores and computational modelling to predict an individual's trajectory of cognitive function. This could help identify individuals who are at risk for cognitive decline, which could then inform better interventions.Read moreRead less
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
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
Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control h ....Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control holistic physiological responses is largely unknown. By deciphering how neural networks are formed this project aims to provide broad biological insight to wiring of the entire nervous system which is likely to have significant implications for the formation of synthetic neural networks and for regeneration.Read moreRead less
Novel computational tools for the analysis of sympathetic nervous system activity. This project will investigate electrical signals from the heart, resulting in novel tools for the assessment of sympathetic nervous system activity. The findings will contribute to advancing Australia's international leading position in health technology and improve community health.
Central pathways regulating visceral pain. This project aims to investigate the neural pathways within the spinal cord and brain processing colorectal pain perception. The project aims to identify the spinal cord neurons relaying colorectal signalling into the brain and the influence of descending modulation from the brainstem upon these pathways. The outcomes will greatly benefit fundamental understanding of the central pathways processing visceral pain.
Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.Read moreRead less