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.
Understanding the Chemical Processes Involved in the Metabolism of Peptide Hormones. Peptide hormones regulate normal physiological activity in humans, and their over-production causes diseases such as cancer. The aims of this project are: to delineate the chemical processes through which these hormones are produced; to develop inhibitors of enzymes involved in hormone production, and agonists and antagonists of receptors through which the hormones act; and to study the ability of the inhibitors ....Understanding the Chemical Processes Involved in the Metabolism of Peptide Hormones. Peptide hormones regulate normal physiological activity in humans, and their over-production causes diseases such as cancer. The aims of this project are: to delineate the chemical processes through which these hormones are produced; to develop inhibitors of enzymes involved in hormone production, and agonists and antagonists of receptors through which the hormones act; and to study the ability of the inhibitors, agonists and antagonists to override and bypass the chemical control mechanisms through which hormone levels are usually maintained at homeostasis. The research is expected to lead to a better fundamental understanding of hormone metabolism, and to underpin the basis for the development of new disease therapies.Read moreRead less
A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough ....A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough and responsive hydrogel platform from this disordered protein family through greater understanding of structure and mechanical function and incorporating adequate stiffness, strength and biocompatibility. Such tough hydrogels would be applicable to a range of biotechnological applications (eg intervertebral disc repair or artificial skin tissue engineering).Read moreRead less
Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for ....Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for the construction and modification of peptides and proteins by harnessing the energy in a unique class of strained molecules. A focus on peptide-based inhibitors of the proteasome, a critical target for modern cancer treatments, should provide future health and economic benefits for the Australian community.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100092
Funder
Australian Research Council
Funding Amount
$418,107.00
Summary
A radical approach to unnatural amino acids and peptide-based antibiotics. This project aims to develop a new synthetic approach to valuable amino acid derivatives and their rapid incorporation into peptide analogues, including promising new antibiotic candidates. This project expects to generate knowledge in the chemical and biological sciences and build scientific capacity to address the global rise of antimicrobial resistance. It is anticipated that this will provide direct health and economi ....A radical approach to unnatural amino acids and peptide-based antibiotics. This project aims to develop a new synthetic approach to valuable amino acid derivatives and their rapid incorporation into peptide analogues, including promising new antibiotic candidates. This project expects to generate knowledge in the chemical and biological sciences and build scientific capacity to address the global rise of antimicrobial resistance. It is anticipated that this will provide direct health and economic benefits by establishing a powerful platform for peptide drug design.Read moreRead less
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.
A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societa ....A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societal benefit as a fundamental scientific platform, improving Australia's capacity and impact in the agriculture and the healthcare sectors. The platform technology has the potential to increase the quality of life for patients and their carers, while also produce fitter, healthier livestock.Read moreRead less
Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to mem ....Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to membrane potential changes. Recently reported crystal structures of bacterial Nav channels have greatly advanced the field, but these channels contain four identical VSDs and have different inactivation properties. Thus, much remains to be learnt about the conformational plasticity of eukaryotic Nav channel VSDs. The project plans to use animal toxins to capture eukaryotic VSDs in defined states of the gating cycle for detailed structural analysis using nuclear magnetic resonance and X-ray crystallography.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100190
Funder
Australian Research Council
Funding Amount
$620,000.00
Summary
Electrophysiology Platform for Ion-channel Characterisation. Ion channels are ubiquitous pore-forming membrane proteins, with the human genome encoding >300 ion channels. The diverse roles of ion channels include action potential generation, control of ion flow across secretory and epithelial cells, and regulation of cell volume, motility and proliferation. Pharmacological modulators are powerful tools for probing ion channel function, but for most channels these tools are lacking. Thus, this p .... Electrophysiology Platform for Ion-channel Characterisation. Ion channels are ubiquitous pore-forming membrane proteins, with the human genome encoding >300 ion channels. The diverse roles of ion channels include action potential generation, control of ion flow across secretory and epithelial cells, and regulation of cell volume, motility and proliferation. Pharmacological modulators are powerful tools for probing ion channel function, but for most channels these tools are lacking. Thus, this project aims to develop the first comprehensive toolbox of ion channel modulators using an integrated in vitro/in vivo electrophysiology platform. These pharmacological tools will be made freely available to the Australian research community for probing the mechanism and physiological function of ion channels.Read moreRead less