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Discovery and characterisation of novel spider-venom peptides targeting the human sodium ion channel Nav1.7. Drugs that selectively block the human sodium ion channel Nav1.7 are likely to be powerful analgesics for treating a wide variety of pain conditions. However, it has proved difficult to obtain selective blockers of this channel. The aim of this project is to determine whether spider-venoms might provide a source of highly selective Nav1.7 blockers.
Characterisation of monoaminergic transmission in Central Amygdala. This project will identify the distribution and function of dopamine, serotonin and noradrenalin receptors on the various cell types and their inputs, in the medial, lateral and capsular divisions of Central Amygdala (CeA). We will test for tonic endogenous activation of monoaminergic receptors and synaptic release from electrically stimulated fibers terminating in CeA. Using paired recordings and calcium imaging, we will invest ....Characterisation of monoaminergic transmission in Central Amygdala. This project will identify the distribution and function of dopamine, serotonin and noradrenalin receptors on the various cell types and their inputs, in the medial, lateral and capsular divisions of Central Amygdala (CeA). We will test for tonic endogenous activation of monoaminergic receptors and synaptic release from electrically stimulated fibers terminating in CeA. Using paired recordings and calcium imaging, we will investigate intracellular mechanisms underlying monoamine receptor mediated effects. These findings when correlated with published behavioural studies will provide greater understanding of the role of the divisions of CeA and the inputs they receive, in the function of the amygdala.Read moreRead less
Activation mechanisms of Cys-loop ion channel receptors. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that proteins work. The information and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Cys-loop ligand-gated receptors have an essential role in brain function and are targets for many therapies and drug ....Activation mechanisms of Cys-loop ion channel receptors. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that proteins work. The information and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Cys-loop ligand-gated receptors have an essential role in brain function and are targets for many therapies and drugs of abuse. New insights into how biological ligands and drugs affect ion channel structure and function may lead to novel therapeutic opportunities and improved drug structure predictions.Read moreRead less
Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhi ....Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhibit myopia, with the aim of determining an ocular measure that is related to myopia, which is altered by drugs that are known to slow myopia progression, and that could be used as an indication of an agent's likely effectiveness.Read moreRead less
Probing norepinephrine transporter (NET) structure-function. More selective drugs are needed to improve the treatment of a range of diseases including pain, depression and anxiety. This project will apply advanced molecular pharmacology approaches to better understand how the norepinephrine transporter functions and where small molecules and conotoxins bind to inhibit its activity.
Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a ....Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Conotoxins: Novel probes for ion channel structure and function. Voltage-dependent and ligand-gated ion channels are intrinsic membrane proteins that play a central role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are (i) to define at a molecular level, the structural and functional determinants of ion channel/conotoxin interactions and (ii) develop new probes that advance neurophysiological research. The diversity and distribution o ....Conotoxins: Novel probes for ion channel structure and function. Voltage-dependent and ligand-gated ion channels are intrinsic membrane proteins that play a central role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are (i) to define at a molecular level, the structural and functional determinants of ion channel/conotoxin interactions and (ii) develop new probes that advance neurophysiological research. The diversity and distribution of ion channel types and subtypes being uncovered through the use of molecular biology and conotoxin probes presents an exciting opportunity for the future development of novel ion channel therapeutics.Read moreRead less
New modulators of voltage-gated sodium channel subtypes from Australian Tarantula venoms. The venoms of Australian tarantula spiders provide a unique and untapped source of bioactive molecules. From a large stock of venom, and in collaboration with Australian pharmaceutical company Xenome, we will develop a comprehensive library of venom components suitable for drug screening. Potential national benefits from this work include a huge reduction in the healthcare bill deriving from a new treatmen ....New modulators of voltage-gated sodium channel subtypes from Australian Tarantula venoms. The venoms of Australian tarantula spiders provide a unique and untapped source of bioactive molecules. From a large stock of venom, and in collaboration with Australian pharmaceutical company Xenome, we will develop a comprehensive library of venom components suitable for drug screening. Potential national benefits from this work include a huge reduction in the healthcare bill deriving from a new treatment for pain, as well as substantial royalty returns from drugs sales. Discoveries from the program are also likely to lead to an enhancement in Australia's reputation in the neurosciences and to the development of new diagnostic research tools. The major community benefit will be a reduction in the suffering of chronic pain patients.Read moreRead less
Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a gr ....Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100422
Funder
Australian Research Council
Funding Amount
$447,346.00
Summary
Using toxins to manipulate the gating of voltage-gated sodium channels. The project aims to investigate how sodium channel subtypes contribute to the excitability of sensory neurons by utilising venom-derived peptides that specifically target and alter the function of these channels. This project expects to generate new knowledge in the area of neuroscience using an interdisciplinary approach including synthetic peptide chemistry, pharmacology and electrophysiology. Expected outcomes of this pro ....Using toxins to manipulate the gating of voltage-gated sodium channels. The project aims to investigate how sodium channel subtypes contribute to the excitability of sensory neurons by utilising venom-derived peptides that specifically target and alter the function of these channels. This project expects to generate new knowledge in the area of neuroscience using an interdisciplinary approach including synthetic peptide chemistry, pharmacology and electrophysiology. Expected outcomes of this project include the development of new venom-based research tools and improved techniques for studying sodium channel function. This will provide significant benefits, including advancement of fundamental knowledge in physiology and the development of novel analgesics. Read moreRead less