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Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhi ....Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhibit myopia, with the aim of determining an ocular measure that is related to myopia, which is altered by drugs that are known to slow myopia progression, and that could be used as an indication of an agent's likely effectiveness.Read moreRead less
Relaxin: molecular mechanisms of cardioprotection. Heart failure represents a major health and economic burden worldwide, for which there is currently no successful cure. This project will provide valuable information on the basic mechanisms associated with the vascular actions of the hormone relaxin that has shown great promise in clinical trials as a novel treatment for heart failure.
Systematic evaluation of whether in vitro methods can predict in vivo opioid analgesic efficacy, safety and tolerability. It is estimated that chronic pain affects one in five individuals in the general community in Australia and worldwide, with prevalence rates correlated directly with advancing age. Chronic pain not only adversely affects the quality of life of individuals but it also places a large economic burden on our healthcare system. Development and validation of an in vitro method to ....Systematic evaluation of whether in vitro methods can predict in vivo opioid analgesic efficacy, safety and tolerability. It is estimated that chronic pain affects one in five individuals in the general community in Australia and worldwide, with prevalence rates correlated directly with advancing age. Chronic pain not only adversely affects the quality of life of individuals but it also places a large economic burden on our healthcare system. Development and validation of an in vitro method to successfully identify novel morphine-like strong analgesics with a reduced propensity for producing respiratory depression or constipation, has the potential to not only improve pain management for individuals and to reduce the economic burden of chronic pain on the Australian healthcare system, but it is also likely to produce direct economic benefits to our nation. Read moreRead less
Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric ....Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric oxide regulates large artery stiffness and we believe that other endothelial mediators are also important regulators. Therefore, we aim to explore this in a series of studies. Regulation of stiffness of large arteries will improve treatment of age-related cardiovascular disease (eg isolated systolic hypertension)Read moreRead less
Oxytocin receptor PET ligands: imaging the love receptor’s engagement. This project aims to develop a positron emission tomography (PET) ligand for the oxytocin receptor. This novel platform is significant as it will allow the scientific community to answer questions about the role of the oxytocin receptor in the important process of social behaviour which underlies quality of life. This knowledge gap has remained unanswered for decades due to the lack of specific techniques to measure oxytocin ....Oxytocin receptor PET ligands: imaging the love receptor’s engagement. This project aims to develop a positron emission tomography (PET) ligand for the oxytocin receptor. This novel platform is significant as it will allow the scientific community to answer questions about the role of the oxytocin receptor in the important process of social behaviour which underlies quality of life. This knowledge gap has remained unanswered for decades due to the lack of specific techniques to measure oxytocin receptor engagement. It is also significant as it will equip Australian startup Kinoxis Therapeutics to progress their molecules to market, a process enabled by measuring oxytocin receptor engagement. Our dual expertise on the oxytocin receptor and PET ligand development uniquely situate us to generate this technology.Read moreRead less
Subtype selectivity and functional bias of receptor positive allosteric modulators for understanding models of pulmonary disease. G-protein-coupled receptors (GPCRs) are an important superfamily of proteins that are involved in a myriad of physiological processes and a wide range of serious illnesses. This project seeks to gain a more detailed understanding of new mechanisms of GPCR modulation and function that will be of direct relevance to drug discovery.
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.
Pharmacological probes to facilitate preclinical development of modulators of a6 subunit containing nicotinic acetylcholine receptors. Allosteric modulators of alpha7 nicotinic acetylcholine receptors have a promising future as drugs targeting attention deficits in Alzheimer’s disease and schizophrenia but the mechanisms underlying modulation are poorly understood. This project aims to determine its binding site and develop a radioactive labelled compound that competes with its binding. The radi ....Pharmacological probes to facilitate preclinical development of modulators of a6 subunit containing nicotinic acetylcholine receptors. Allosteric modulators of alpha7 nicotinic acetylcholine receptors have a promising future as drugs targeting attention deficits in Alzheimer’s disease and schizophrenia but the mechanisms underlying modulation are poorly understood. This project aims to determine its binding site and develop a radioactive labelled compound that competes with its binding. The radiolabelled compound and a deeper insight into the mode of action will enable development of ligands for positron emission tomography (PET) which will aid in the development of BNC375 as well as other alpha7 modulators.Read moreRead less
Structural modification of conus-derived venom peptides- A route to new therapeutics. Current product deficiencies in the area of pain management are forcing the pharmaceutical industry to develop new strategies for achieving analgesia and reduce their dependence on traditional, addictive opiate-based products. Structural modification of Conus derived peptides will provide exciting new leads for achieving effective analgesia.
NOVEL THERAPEUTICS FOR AUTOIMMUNE DISEASE USING MOUSE SCREENING MODELS. The project aims to use experimental models of human autoimmune disease in the mouse for the testing of developmental isoflavonoid compounds produced by the Industry Partner, for protective effects against autoimmunity. The murine models proposed will duplicate human autoimmune cardiomyopathy, systemic lupus erythematosus and multiple sclerosis, encompassing both organ-specific and systemic autoimmune diseases. Isoflavonoi ....NOVEL THERAPEUTICS FOR AUTOIMMUNE DISEASE USING MOUSE SCREENING MODELS. The project aims to use experimental models of human autoimmune disease in the mouse for the testing of developmental isoflavonoid compounds produced by the Industry Partner, for protective effects against autoimmunity. The murine models proposed will duplicate human autoimmune cardiomyopathy, systemic lupus erythematosus and multiple sclerosis, encompassing both organ-specific and systemic autoimmune diseases. Isoflavonoid protection is anticipated from the antioxidant, anti-inflammatory and oestrogenic characteristics of these compounds/Read moreRead less