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
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.
Discovery And Development Of Better Pain Treatments
Funder
National Health and Medical Research Council
Funding Amount
$9,613,850.00
Summary
Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clini ....Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clinical potential.Read moreRead less
Development of chaperonin 10-based second generation biopharmaceuticals for treatment of inflammatory diseases. Diseases caused by malfunctioning of the body's immune system (inflammatory diseases) such as rheumatoid arthritis, psoriasis and Crohn's disease cause illness in all cultures and societies, and impose financial strain on health care providers. Current treatment relies on biopharmaceuticals that block inflammatory mediators in the body or with pharmaceuticals such as anti-inflammatory ....Development of chaperonin 10-based second generation biopharmaceuticals for treatment of inflammatory diseases. Diseases caused by malfunctioning of the body's immune system (inflammatory diseases) such as rheumatoid arthritis, psoriasis and Crohn's disease cause illness in all cultures and societies, and impose financial strain on health care providers. Current treatment relies on biopharmaceuticals that block inflammatory mediators in the body or with pharmaceuticals such as anti-inflammatory drugs; both these treatments may have serious side effects. Cpn10 suppresses the body's inflammatory response while maintaining immune function to combat infections. The project seeks to develop new, safe and effective biopharmaceuticals based on Cpn10 for the treatment of a variety of chronic inflammatory diseases and autoimmune disorders.Read moreRead less
Characterisation of the anti-inflammatory pathway targeted by chaperonin 10 (Cpn10). Diseases associated with excessive or inappropriate inflammation represent an enormous socioeconomic burden, and there is currently an urgent need to identify new targets for the development of more efficacious and safe treatments. This research seeks to provide such targets. The research may also lead to improvements in chaperonin 10 (Cpn10) treatment, which has already showing marked success in chronic inflamm ....Characterisation of the anti-inflammatory pathway targeted by chaperonin 10 (Cpn10). Diseases associated with excessive or inappropriate inflammation represent an enormous socioeconomic burden, and there is currently an urgent need to identify new targets for the development of more efficacious and safe treatments. This research seeks to provide such targets. The research may also lead to improvements in chaperonin 10 (Cpn10) treatment, which has already showing marked success in chronic inflammatory disease trials. Importantly, Cpn10 appears to be anti-inflammatory rather than immunosuppressive; a critical advantage over many current anti-inflammatory interventions. Immunosuppression can lead to increased infections, which can have serious consequences, especially in elderly patients.Read moreRead less
Innovations in peptide-based drug design. This project will aim to develop new types of drugs that fill a gap between existing small molecule drugs, which are relatively inexpensive and stable, but often have side-effects, and biologics which are very expensive and require injection. Our new generation of peptide-based drugs promise to be applicable to diseases that are not treatable by current drugs.
Structure and function of predatory and defensive venoms in cone snails. This project aims to investigate newly-discovered cone snail venoms to accelerate the search for novel bioactive peptides. It was recently discovered that cone snails can rapidly and reversibly switch between distinct venoms in response to predatory or defensive stimuli, implying that defensive and predatory venoms have evolved under separate selection pressures. The project plans to obtain separate predatory and defensive ....Structure and function of predatory and defensive venoms in cone snails. This project aims to investigate newly-discovered cone snail venoms to accelerate the search for novel bioactive peptides. It was recently discovered that cone snails can rapidly and reversibly switch between distinct venoms in response to predatory or defensive stimuli, implying that defensive and predatory venoms have evolved under separate selection pressures. The project plans to obtain separate predatory and defensive venoms and venom duct tissue from individual cone snails to compare and contrast the structure and function of conotoxins evolved for predation versus those evolved for defence, to elucidate the structure and function of these important classes of bioactive peptides.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