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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.
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
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.
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.
New modulators of voltage-gated sodium channel subtypes from Australian Tarantula venoms. The venoms of Australian tarantula spiders provide a unique and untapped source of bioactive molecules. From a large stock of venom, and in collaboration with Australian pharmaceutical company Xenome, we will develop a comprehensive library of venom components suitable for drug screening. Potential national benefits from this work include a huge reduction in the healthcare bill deriving from a new treatmen ....New modulators of voltage-gated sodium channel subtypes from Australian Tarantula venoms. The venoms of Australian tarantula spiders provide a unique and untapped source of bioactive molecules. From a large stock of venom, and in collaboration with Australian pharmaceutical company Xenome, we will develop a comprehensive library of venom components suitable for drug screening. Potential national benefits from this work include a huge reduction in the healthcare bill deriving from a new treatment for pain, as well as substantial royalty returns from drugs sales. Discoveries from the program are also likely to lead to an enhancement in Australia's reputation in the neurosciences and to the development of new diagnostic research tools. The major community benefit will be a reduction in the suffering of chronic pain patients.Read moreRead less
New insulins for the improved management of diabetes. The prevalence of diabetes has increased dramatically over the past few decades and now this condition is widely considered the world’s fastest growing disease. New insulins with improved pharmacological and storage properties are desperately needed, and this project will work on chemical synthesis enabling designer insulins to be prepared for improved management of diabetes.
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
Treating Equine Laminitis. This project aims to explore the causes of equine laminitis, and to work with a newly-established Australian biopharma company to develop the world's first anti-laminitis medication. Equine laminitis is a painful, crippling disease of the foot, often necessitating euthanasia, and is the second-most common cause of death in domestic horses. In 2007, a landmark study identified insulin toxicity as a primary cause of laminitis, and subsequent research has identified over- ....Treating Equine Laminitis. This project aims to explore the causes of equine laminitis, and to work with a newly-established Australian biopharma company to develop the world's first anti-laminitis medication. Equine laminitis is a painful, crippling disease of the foot, often necessitating euthanasia, and is the second-most common cause of death in domestic horses. In 2007, a landmark study identified insulin toxicity as a primary cause of laminitis, and subsequent research has identified over-stimulation of the IGF-1 receptor as the most likely mechanism. This project aims to prove that mechanism and to develop an effective treatment.Read moreRead less
Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hya ....Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hyaluronan) of the interstitum, can be used promote absorption into the draining blood and lymph capillaries. The project aims to also explore the downstream effects of hyaluronidase on lymph nodes and evaluate whether the enzyme is able to temporarily disrupt the lymph node structure and promote drug penetration into the lymph node mass. This has significant potential for improved drug targeting.Read moreRead less
Translation of evidence into pain management practices in acute care environments. This project addresses the urgent need to reduce the substantial pain experienced by patients following surgery by improving the clinical processes associated with the treatment of pain. Each year in Australia, six million people are admitted to hospital for surgery. A recent review of Australian research has shown that up to 40% of hospitalised surgical patients experience significant pain. Despite the availabili ....Translation of evidence into pain management practices in acute care environments. This project addresses the urgent need to reduce the substantial pain experienced by patients following surgery by improving the clinical processes associated with the treatment of pain. Each year in Australia, six million people are admitted to hospital for surgery. A recent review of Australian research has shown that up to 40% of hospitalised surgical patients experience significant pain. Despite the availability of effective treatment, pain after surgery is often under-treated and is one of the main postoperative adverse outcomes. A consequence of poor pain management is that patients experience unnecessary suffering, higher incidence of postoperative complications significant risk of developing chronic post-surgical pain.Read moreRead less