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
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
Molecular and immunological approaches to managing Australia's seafood allergy epidemic. Seafood is an increasingly important cause of food allergy. Novel insight into the functions of why and how proteins from seafood develop to potent allergens will lead to the development of better diagnostics and therapeutics. This will assist patients to better manage their serious food allergy.
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
Engineering peptides into superglues selective for target proteins. This project aims to discover how to create long-acting peptides for future research tools, drugs, biosensors and diagnostics. Peptides are currently viewed by the general community as injectable performance-enhancing drugs which are difficult to detect because they don't last very long. However, peptides have many potential benefits that are difficult to obtain because of their short durations of action. This project aims to de ....Engineering peptides into superglues selective for target proteins. This project aims to discover how to create long-acting peptides for future research tools, drugs, biosensors and diagnostics. Peptides are currently viewed by the general community as injectable performance-enhancing drugs which are difficult to detect because they don't last very long. However, peptides have many potential benefits that are difficult to obtain because of their short durations of action. This project aims to develop ways of engineering peptide shapes into nanoscale superglues that stick more tightly but selectively to their target proteins, thereby extending their durations of action. Technology for engineering superglues would produce proof of concept and prototypes for future research tools, drugs, diagnostics and biosensors.Read moreRead less