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Potent Small Molecule Modulators Of A Complement Protein In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$689,428.00
Summary
We have invented powerful new compounds that act on the cell surface and regulate inflammation. We plan to (1) fine-tune our small molecules for optimal activity on different kinds of immune cells; (2) understand mechanisms by which the compounds affect cellular inflammatory responses; (3) evaluate the compounds as potential treatments in rodent models of inflammatory diseases implicated from cell studies. This study is anticipated to lead to clinical studies for a new kind of drug treatment.
Unraveling Fibrosis By Pharmacological Targeting Of The G Protein-coupled Receptor, RXFP1
Funder
National Health and Medical Research Council
Funding Amount
$798,618.00
Summary
Peptides, with their high specificity and low toxicity profiles, are highly attractive alternatives to small molecule drugs. H2 relaxin, a peptide hormone, has a strong potential for treating fibrosis. However, the large size of H2 relaxin makes it difficult and expensive to manufacture. Once administered to patients, it is also quickly degraded. We have developed a small anti-fibrotic relaxin peptide, and propose to understand its mechanism of action and improve its therapeutic indices.
Modulation Of Feeding Through Pharmacological Targeting Of The Relaxin-3 Receptor RXFP3
Funder
National Health and Medical Research Council
Funding Amount
$584,955.00
Summary
Relaxin-3 is a neuropeptide that regulates a number of physiological processes, including food intake, suggesting that the relaxin-3 receptor RXFP3 may be a new target for treatment of eating disorders such as obesity. This project will develop new selective and high-affinity ligands for RXFP3, which will be critical pharmacological tools for the preclinical studies and evaluation of this system.
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
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.
Molecular probe development for high specificity and spatiotemporal control. This project aims at developing next-generation molecular probes with enhanced specificity and spatiotemporal control for the study of proteins and neuropeptide signalling. It addresses recognised knowledge gaps and technical bottlenecks in neuropeptide and memory research. Expected outcomes include a deeper molecular understanding of long-term memory formation and the role of neuropeptides in this process, as well as i ....Molecular probe development for high specificity and spatiotemporal control. This project aims at developing next-generation molecular probes with enhanced specificity and spatiotemporal control for the study of proteins and neuropeptide signalling. It addresses recognised knowledge gaps and technical bottlenecks in neuropeptide and memory research. Expected outcomes include a deeper molecular understanding of long-term memory formation and the role of neuropeptides in this process, as well as innovative chemistry strategies and novel molecular probes to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations of relevance to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.Read moreRead less
Plant peptides as modulators of invertebrate neurohormone receptors. Naturally-occurring peptides are widely distributed in many plants, but their biological role is often unclear. Circular plant peptides (called cyclotides) that share similarities with the neuropeptide oxytocin, and acts on its receptor, have been previously isolated. This signalling system is important for reproduction, development, and behaviour as well as water homeostasis. To elucidate the natural function of cyclotides. Th ....Plant peptides as modulators of invertebrate neurohormone receptors. Naturally-occurring peptides are widely distributed in many plants, but their biological role is often unclear. Circular plant peptides (called cyclotides) that share similarities with the neuropeptide oxytocin, and acts on its receptor, have been previously isolated. This signalling system is important for reproduction, development, and behaviour as well as water homeostasis. To elucidate the natural function of cyclotides. This project aims to characterise the pharmacological properties and biological effects of invertebrate receptors and their modulation by cyclotides. The notion that plants produce molecules to target invertebrate receptors is extremely appealing and will enhance knowledge about fundamental biological processes of plant-animal ecology.Read moreRead less
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