A new class of sodium channel toxin from ant venoms . Ants are diverse and ubiquitous and the ability of certain species to sting is familiar to many of us. Yet we know remarkably little about the chemistry underlying these stings. We recently discovered that the venoms of ants, including common Australian species, harbour a novel and unique class of sodium channel toxins. Building on this discovery, the aim of this project will be to perform an in-depth characterisation of the effects of these ....A new class of sodium channel toxin from ant venoms . Ants are diverse and ubiquitous and the ability of certain species to sting is familiar to many of us. Yet we know remarkably little about the chemistry underlying these stings. We recently discovered that the venoms of ants, including common Australian species, harbour a novel and unique class of sodium channel toxins. Building on this discovery, the aim of this project will be to perform an in-depth characterisation of the effects of these toxins on sodium channels and to uncover the diversity and breadth of this toxin class in ant venoms. The outcome of this project will be novel insights into the chemistry of ant venoms and new insights into sodium channel function.Read moreRead less
Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to ....Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to uncover toxins that employ new mechanisms of pain signalling, leading to new insights into pain physiology.Read moreRead less
Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much ac ....Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much acclaimed and novel pathway that allows efficient, combined cytokine secretion and phagocytosis in macrophages. Our studies proposed here will now expand on this discovery by comparing the phagocytic process, in terms of SNARE-mediated membrane and cytokine trafficking, for a wide range of microbes, highlighting differences that could provide new avenues for drug development. Moreover, since our strategy of using SNAREs to investigate and map trafficking pathways has proven so successful, we will now launch a major large-scale initiative to study ALL SNARE-mediated trafficking pathways in macrophages using a discovery pipeline of assays, including live cell imaging, we have developed. This will provide valuable information on many SNAREs including those associated with disease, and will elucidate trafficking pathways governing all macrophage actions in immunity, including cytokine secretion and antigen presentation. All of these pathways are highly relevant to current drug targets being used clinically or studied in inflammatory disease and for the development of vaccines.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
Toxins from Down Under: Novel tools to understand and modulate ion channels. Venoms are complex secretions containing biologically active components that have evolved over millions of years to specifically target the nervous systems of predators and prey. Two novel classes of toxins from snake and plant venoms that act on voltage-gated sodium channels, key proteins that regulate neuronal excitability, were recently identified by the research team. The project aims to develop and apply state-of-t ....Toxins from Down Under: Novel tools to understand and modulate ion channels. Venoms are complex secretions containing biologically active components that have evolved over millions of years to specifically target the nervous systems of predators and prey. Two novel classes of toxins from snake and plant venoms that act on voltage-gated sodium channels, key proteins that regulate neuronal excitability, were recently identified by the research team. The project aims to develop and apply state-of-the-art chemical, structural and biological techniques to unravel the molecular mechanisms through which these novel toxin classes act at their targets. Insights gained from this project will help identify and develop novel channel-modulating molecules that may have applications as neuroscience tools, diagnostics or drugs.Read moreRead less
The potential of membranes – peptide engineering to modulate ion channels. This project aims to develop a platform technology to identify new and selective sodium channel inhibitors based on ultra-stable venom peptides that can interact with and cross membranes. Sodium channels are involved in almost all aspects of human physiology. The ability to selectively inhibit individual sodium channel subtypes and to understand what drives peptides' ability to cross membranes would be a major achievement ....The potential of membranes – peptide engineering to modulate ion channels. This project aims to develop a platform technology to identify new and selective sodium channel inhibitors based on ultra-stable venom peptides that can interact with and cross membranes. Sodium channels are involved in almost all aspects of human physiology. The ability to selectively inhibit individual sodium channel subtypes and to understand what drives peptides' ability to cross membranes would be a major achievement and lead to new neuroscience research tools and technologies. This project’s proposed technology could be translated into new knowledge relevant to the biotechnology industry.Read moreRead less
Defining a new family of sodium channel accessory proteins. Voltage-gated sodium channels are key proteins that function as multi-subunit complexes to regulate neuronal excitability. The project aims to investigate the structure and function of a novel family of accessory subunits by utilizing a class of toxins, derived from the giant Australian stinging tree, that directly binds to these proteins to modulate sodium channel function. The project aims to generate significant new knowledge on the ....Defining a new family of sodium channel accessory proteins. Voltage-gated sodium channels are key proteins that function as multi-subunit complexes to regulate neuronal excitability. The project aims to investigate the structure and function of a novel family of accessory subunits by utilizing a class of toxins, derived from the giant Australian stinging tree, that directly binds to these proteins to modulate sodium channel function. The project aims to generate significant new knowledge on the function of sodium channels as multi-protein complexes. Expected outcomes of this project include development of novel channel-modulating molecules that may have applications as neuroscience tools to address fundamental questions about ion channel function and biology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150100784
Funder
Australian Research Council
Funding Amount
$373,254.00
Summary
Molecular probe development for the oxytocin and vasopressin receptors. The oxytocin and vasopressin receptors are part of a 600 million year old signalling system that is widely distributed in the kingdom of life. It is involved in many fundamental physiological functions, however we still lack a complete toolbox of selective probes to delineate the individual receptor subtypes. This project aims to introduce a novel and innovative strategy that uses state-of-the art discovery techniques to ide ....Molecular probe development for the oxytocin and vasopressin receptors. The oxytocin and vasopressin receptors are part of a 600 million year old signalling system that is widely distributed in the kingdom of life. It is involved in many fundamental physiological functions, however we still lack a complete toolbox of selective probes to delineate the individual receptor subtypes. This project aims to introduce a novel and innovative strategy that uses state-of-the art discovery techniques to identify selective ligands in nature. Leads will be developed into molecular probes to facilitate in-depth studies of this system. This strategy is applicable to other systems and the outcomes will contribute to a significant advancement of knowledge in chemical biology.Read moreRead less