Discovery Early Career Researcher Award - Grant ID: DE160101142
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Unravelling the structural evolution of centipede toxins. The project intends to improve understanding of venom evolution in centipedes, and uncover new families of peptides with potential application in the agrochemical and pharmaceutical sectors. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range studied, and many groups of venomous a ....Unravelling the structural evolution of centipede toxins. The project intends to improve understanding of venom evolution in centipedes, and uncover new families of peptides with potential application in the agrochemical and pharmaceutical sectors. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range studied, and many groups of venomous animals remain overlooked. One such group is centipedes, whose venoms contain diverse novel toxins. This project aims to provide an insight into centipede toxin evolution, and establish a structure-based approach to understanding their evolution and structural diversification. The outcomes may contribute to our understanding of protein evolution and support the development of new products.Read moreRead less
Nettles & toxic toupees: the molecular weaponry of venomous caterpillars. This project aims to investigate the structure, function and evolution of peptide toxins in venoms made by caterpillars in superfamily Zygaenoidea. Caterpillars in this group are covered in spines that inject pain-causing venoms, and this protects them from vertebrate and invertebrate predators. This project will test if peptides in this venom cause pain by pharmacological modulation of mammalian ion channels and signallin ....Nettles & toxic toupees: the molecular weaponry of venomous caterpillars. This project aims to investigate the structure, function and evolution of peptide toxins in venoms made by caterpillars in superfamily Zygaenoidea. Caterpillars in this group are covered in spines that inject pain-causing venoms, and this protects them from vertebrate and invertebrate predators. This project will test if peptides in this venom cause pain by pharmacological modulation of mammalian ion channels and signalling receptors, and if they have insecticidal properties. The first three-dimensional structures of caterpillar venom peptides will also be solved. Genomes of representatives of two different zygaenoid families will be produced, and genomic techniques will be used to elucidate how venom use evolved at the molecular level.Read moreRead less
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
Unravelling the molecular diversity and evolution of centipede venoms. The project intends to improve understanding of venom evolution in centipedes. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range of animals studied, with many groups of venomous animals overlooked. One such group is centipedes, whose venoms contain diverse toxins th ....Unravelling the molecular diversity and evolution of centipede venoms. The project intends to improve understanding of venom evolution in centipedes. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range of animals studied, with many groups of venomous animals overlooked. One such group is centipedes, whose venoms contain diverse toxins that differ between taxa. This project aims to provide an insight into centipede venom evolution, and how it might be constrained by venom-gland morphology. This study seeks to contribute to our understanding of protein evolution and direct biodiscovery efforts around centipede venom.Read moreRead less
ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the d ....ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the design of peptides and proteins for targeted scientific, agricultural, biotechnology, animal health and pharmaceutical applications. CIPPS will assemble leading researchers from diverse disciplines to create a sustainable national entity that will drive new Australian industries and train next generation researchers.Read moreRead less
A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for t ....A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for their production. The project will use advanced nuclear magnetic resonance spectroscopy to characterise members of this new class, providing new insights into the design of bivalent and multivalent peptides and establishing a new source of molecules with applications in the rapidly growing biotechnology sector.Read moreRead less
Novel conotoxins that target ion channels and receptors. This project will discover peptides from cone snail venom that are potential drug candidates. The project will expand our knowledge of these biological active peptides and their mode of action. It will also protect key molecules through patent applications, providing a competitive edge for Australian biotechnology.
Development of potent and specific modulators of the human sodium channel Nav1.7. There are few effective drugs available for the treatment of chronic pain. This team recently discovered that spider venoms are a rich source of inhibitors of Nav1.7, a new target for anti-pain drugs. The goal of this project is to develop potent blockers of Nav1.7 that can be used to critically assess the role of this ion channel in mediating pain.
Aquatic chemo-modulators: a novel source for potent molecular probes. This project aims to investigate peptides that modulate prey behaviour. Chemical signalling constitutes much of the language of life underwater. Certain cone snails evolved a hunting strategy, where they release potent peptides to modulate fish behaviour through yet unknown mechanisms. The snail then expands its mouth and eats the fish without resistance. This project will investigate the mechanisms at play using transcriptomi ....Aquatic chemo-modulators: a novel source for potent molecular probes. This project aims to investigate peptides that modulate prey behaviour. Chemical signalling constitutes much of the language of life underwater. Certain cone snails evolved a hunting strategy, where they release potent peptides to modulate fish behaviour through yet unknown mechanisms. The snail then expands its mouth and eats the fish without resistance. This project will investigate the mechanisms at play using transcriptomics, proteomics, peptide synthesis, behavioural pharmacology and nuclear magnetic resonance. This will advance the knowledge of aquatic chemo-modulators on a functional, structural and evolutionary level, and provide a source of molecular probes with unique pharmacology and applications in human physiology, developmental biology and aquacultures.Read moreRead less
Novel cysteine-rich conotoxin frameworks from Australian cone snails. This project aims to discover conotoxins that are potential drug leads or useful pharmacological tools. It aims to increase both the discovery of novel conotoxin cysteine-rich frameworks through integrated transcriptomics and proteomics (venomics), conotoxin synthesis and 3-D structure determination, and to generate conotoxin disulfide bond mimetics and conotoxin dendrimers to increase stability, potency and selectivity. The w ....Novel cysteine-rich conotoxin frameworks from Australian cone snails. This project aims to discover conotoxins that are potential drug leads or useful pharmacological tools. It aims to increase both the discovery of novel conotoxin cysteine-rich frameworks through integrated transcriptomics and proteomics (venomics), conotoxin synthesis and 3-D structure determination, and to generate conotoxin disulfide bond mimetics and conotoxin dendrimers to increase stability, potency and selectivity. The work is designed to be based on a venomics platforms to accelerate conotoxin framework discovery while using novel mimetics and dendrimeric constructs to improve their biophysical properties. The expected outcomes include an expansion of novel conotoxin sequences and novel frameworks to generate lead molecules for potential development.Read moreRead less