Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, elec ....G-protein coupled receptor-mediated calcium signalling in parasympathetic neurons. External chemical stimuli act on specific cell-surface receptors of neurons resulting in an increase in the intracellular calcium ion concentration which acts as a second messenger to alter neuronal excitability. There are, however, many receptors acting through a number of closely related proteins involving complex intracellular signalling pathways which remain poorly understood. This project uses molecular, electrical and fluorescence techniques to elucidate the molecular basis for these interactions by identifying the roles individual proteins play in integrating diverse extracellular stimuli and neuronal excitablility in the peripheral nervous system.Read moreRead less
Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thor ....Functional ubiquitination of neuronal voltage-gated sodium channels. Alterations in the electrical properties of excitable cells occur during tissue injury and regeneration as well as many disease states. Preventing or controlling these changes is a key strategic therapeutic aim. It is, however, only through a comprehensive understanding of the molecular mechanisms that regulate cellular excitability that we can identify these therapeutic targets. The major outcome of this project will be a thorough characterisation of a novel pathway that is potentially crucial in the development, homeostasis and regeneration of the nervous system. Disruption of normal function of this system may underlie the hyperexcitability observed in mannu neurodegenerative conditions.Read moreRead less
Sustaining neuronal communication through bulk endocytosis. Brain activities such as learning and memory rely on the ability of neurons to communicate. This research will improve our understanding of how synaptic vesicles recycle during periods of intense synaptic activity. This is a fundamental process relevant to neuronal communication, insulin release, hormone secretion, and allergic responses in health and disease and therefore has broad significance. This work will enhance Australia's exist ....Sustaining neuronal communication through bulk endocytosis. Brain activities such as learning and memory rely on the ability of neurons to communicate. This research will improve our understanding of how synaptic vesicles recycle during periods of intense synaptic activity. This is a fundamental process relevant to neuronal communication, insulin release, hormone secretion, and allergic responses in health and disease and therefore has broad significance. This work will enhance Australia's existing strength in cell biology and neuroscience and provide high quality training for an undergraduate student and post-doctoral scientist.Read moreRead less
Conantokin selectivity for heteromeric N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are ligand gated ion channels formed by heterogeneous population of subunits with distinct pharmacological and biophysical properties. The heterogeneic receptors are differentially expressed during development and play an important role in many physiological and pathological processes. Conantokins are toxins isolated from Conus venoms, which target NMDA receptor subunits with high affinity. The primary g ....Conantokin selectivity for heteromeric N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are ligand gated ion channels formed by heterogeneous population of subunits with distinct pharmacological and biophysical properties. The heterogeneic receptors are differentially expressed during development and play an important role in many physiological and pathological processes. Conantokins are toxins isolated from Conus venoms, which target NMDA receptor subunits with high affinity. The primary goal of this study is to examine the effects of conantokins on the molecular properties of different NMDA receptor subtypes in vivo and in vitro.Read moreRead less