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
Refinement And Delivery Of Synthetic Compounds That Specifically Alter Muscle Contraction. The project has broad benefits for the nation and the community. Cutting edge research at the molecular level, done within Australia, will benefit Australian scientists and research in general. The discovery of drugs that will be developed by the Australian Pharmaceutical Industry will benefit the Australian Industry sector and will have spin-offs for the racing industry, livestock industry (lean meat) an ....Refinement And Delivery Of Synthetic Compounds That Specifically Alter Muscle Contraction. The project has broad benefits for the nation and the community. Cutting edge research at the molecular level, done within Australia, will benefit Australian scientists and research in general. The discovery of drugs that will be developed by the Australian Pharmaceutical Industry will benefit the Australian Industry sector and will have spin-offs for the racing industry, livestock industry (lean meat) and for rural industry (insecticides). In addition, expansion of the outcomes of the project into preclinical development will strengthen the Australian bioscience sector. Thus the project will eventually benefit the Australian industry sector. The project will have further benefits for education and training. Read moreRead less
Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test th ....Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test the efficacy of three proteins as anti-bleeding agents and investigate several other novel components. The ultimate outcome will be the development of novel drugs that will have application in the treatment of human disorders. Read moreRead less
Transdermal penetration of corticosteroids in the dog. Topical application of corticosteroids enhances drug concentration and effectiveness in the treatment of skin diseases. Most topical corticosteroid preparations have been developed for human use and are poorly efficacious or promote a high incidence of adverse effects in dogs. This project will characterize corticosteroid penetration through canine skin to permit the development of suitable topical formulations to more effectively control ....Transdermal penetration of corticosteroids in the dog. Topical application of corticosteroids enhances drug concentration and effectiveness in the treatment of skin diseases. Most topical corticosteroid preparations have been developed for human use and are poorly efficacious or promote a high incidence of adverse effects in dogs. This project will characterize corticosteroid penetration through canine skin to permit the development of suitable topical formulations to more effectively control skin diseases in the dog. Skin diseases are a significant problem in veterinary science and this project will not only provide an effective therapeutic option, but also reduce animal (and client) distress when suffering skin disease and/or adverse effects from traditional therapy.Read moreRead less
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.
Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in ....Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in order to develop more potent drug analogues. Development of these molecules will involve a collaborative and multidisciplinary link with our industry partner and the use of frontier technologies that may lead to improved health and economic outcomes for Australia. Read moreRead less
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
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
Exploitation of a Novel Drug Target for Controlling Animal Trypanosomiasis. Trypanosomiasis greatly reduces livestock productivity in countries where it is endemic and is a threat to livestock and native wildlife in countries such as Australia where it is exotic but there is a risk of entry. New trypanocidal drugs with different modes of action are urgently needed to overcome growing resistance. This project aims to characterise trypanosome tubulin and, with this information, produce new tubulin ....Exploitation of a Novel Drug Target for Controlling Animal Trypanosomiasis. Trypanosomiasis greatly reduces livestock productivity in countries where it is endemic and is a threat to livestock and native wildlife in countries such as Australia where it is exotic but there is a risk of entry. New trypanocidal drugs with different modes of action are urgently needed to overcome growing resistance. This project aims to characterise trypanosome tubulin and, with this information, produce new tubulin-binding compounds for assessment in vitro and in vivo. Upon completion of the project it is expected that drug binding sites on trypanosome tubulin will be characterised and at least one candidate for clinical trials identified.Read moreRead less