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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Microfluidic models of the CNS: Understanding cells, circuits & synapses. Aims: We aim to develop new cell culture platforms to form defined networks of brain cells. These platforms will be used to determine the critical mechanisms underpinning central nervous system function.
Significance: The devices developed will enable an unprecedented capacity to monitor changes throughout a network, with analysis at the level of the synapse, cell and circuit.
Expected outcomes: We will advance knowledge ....Microfluidic models of the CNS: Understanding cells, circuits & synapses. Aims: We aim to develop new cell culture platforms to form defined networks of brain cells. These platforms will be used to determine the critical mechanisms underpinning central nervous system function.
Significance: The devices developed will enable an unprecedented capacity to monitor changes throughout a network, with analysis at the level of the synapse, cell and circuit.
Expected outcomes: We will advance knowledge regarding the function of the CNS and deliver complex human cellular systems, that have both discovery and commercial applications.
Benefit: These platforms will have subsequent application revealing the mechanisms underlying numerous neurological diseases, with capacity to upscale for rapid drug screening.
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Huntingtin-associated protein 1 controls cell communication. The purpose of this study is to identify the mechanisms by which a novel regulator of cell communication which we have identified is able to control the release of chemical signals from a cell. This project will provide critical insight into a cellular pathway that underlies hormone secretion, neurotransmission and higher brain functions.
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
Understanding the mechanisms of GABA type-A receptor activation and drug modulation. There is currently little understanding of how sedative and anxiolytic drugs, including valium, interact with their receptors in the brain. This project will dramatically increase our understanding of how these receptors work and how drugs affect their activity. This will provide new insights into drug discovery and design.
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
Central Representation of Electroacoustic Stimuli. Cochlear implantation, initially only provided to profoundly deaf individuals, is now routine in people with substantial residual hearing. Although stimulation via a cochlear implant and hearing aid in the same ear has been shown to improve speech understanding, particularly in noise, and to increase the aesthetic quality of sound, almost nothing is known about the physiological mechanisms underlying these benefits. The broad aim of our project ....Central Representation of Electroacoustic Stimuli. Cochlear implantation, initially only provided to profoundly deaf individuals, is now routine in people with substantial residual hearing. Although stimulation via a cochlear implant and hearing aid in the same ear has been shown to improve speech understanding, particularly in noise, and to increase the aesthetic quality of sound, almost nothing is known about the physiological mechanisms underlying these benefits. The broad aim of our project is to address this deficiency by measuring the patterns of neural activity evoked by speech sounds across the tonotopic axis in the inferior colliculus and auditory cortex and assess the extent to which the pattern of neural activity allows discrimination between the different speech sounds.Read moreRead less
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less
Neural circuits that mediate fear conditioning and extinction. Understanding of how the brain processes, stores and retrieves information and produces behavioural outcomes is in its infancy. This project will use electrophysiology and molecular techniques to understand the circuits that mediate one form of emotional learning.
Understanding brain mechanisms that control autonomic function. This project aims to understand the how the brain regulates sympathetic nerve activity, thereby increasing our understanding of the biology and function of nascent neurons on the adult brain stem. This challenges the current notion that new neurons are only made during development. The project will also determine how brain inflammation impacts blood-brain barrier function and affects sympathetic nerve regulation. The basic fundament ....Understanding brain mechanisms that control autonomic function. This project aims to understand the how the brain regulates sympathetic nerve activity, thereby increasing our understanding of the biology and function of nascent neurons on the adult brain stem. This challenges the current notion that new neurons are only made during development. The project will also determine how brain inflammation impacts blood-brain barrier function and affects sympathetic nerve regulation. The basic fundamental insights and conceptual advances into how autonomic function is controlled by the brain will provide a better understanding of these fundamental processes and will contribute to Australia’s priority research areas to improve health and advance product development.Read moreRead less