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
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
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
Improving diagnostic accuracy and treatment options for equine PPID. Equine Pituitary Pars Intermedia Dysfunction (PPID) is a common, chronic and potentially life-threatening disease of older horses and ponies. Although a treatment is available, the disease is poorly understood and there are some concerns that the current diagnostic technology is not delivering accurate results. Thus, this project aims to develop a more accurate diagnostic test for PPID, while exploring the relationship between ....Improving diagnostic accuracy and treatment options for equine PPID. Equine Pituitary Pars Intermedia Dysfunction (PPID) is a common, chronic and potentially life-threatening disease of older horses and ponies. Although a treatment is available, the disease is poorly understood and there are some concerns that the current diagnostic technology is not delivering accurate results. Thus, this project aims to develop a more accurate diagnostic test for PPID, while exploring the relationship between PPID and metabolic syndrome, to generate new insights into the cause and consequences of both diseases. As an added benefit, the project will assist horseracing laboratories to improve their detection methods for peptide doping in younger competition horses.
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Development of a topical treatment to replace surgical mulesing in sheep. 10,800 farms in Australia are sheep farms and a further 30,000 have sheep. Exports of wool earn over $2 billion annually. The animal rights campaign to ban mulesing has forced the industry to outlaw mulesing by 2010. Mulesing is largely confined to Australian Merino sheep and requires Australian research. If practical alternatives are not found costs will rise compromising the economic viability of many sheep farms. C ....Development of a topical treatment to replace surgical mulesing in sheep. 10,800 farms in Australia are sheep farms and a further 30,000 have sheep. Exports of wool earn over $2 billion annually. The animal rights campaign to ban mulesing has forced the industry to outlaw mulesing by 2010. Mulesing is largely confined to Australian Merino sheep and requires Australian research. If practical alternatives are not found costs will rise compromising the economic viability of many sheep farms. Chemical use on the breech will increase causing environmental contamination. A simple topical alternative to mulesing will allow farmers to economically manage flies and satisfy welfare imperatives. This will support rural communities and sustain Australia's export income from wool.Read moreRead less
Prevention and treatment of chlamydiosis and cryptococcosis in koalas. This project aims to generate increased understanding of the aetiology and pathogenesis of the two most prevalent and debilitating infectious diseases of koalas to make improved decisions regarding therapeutic intervention, prevention and management. Chlamydiosis, caused by two chlamydial bacteria, affects koala fertility, urinary tract function and eyesight. Cryptococcosis, caused by the fungus Cryptococcus gattii, may resul ....Prevention and treatment of chlamydiosis and cryptococcosis in koalas. This project aims to generate increased understanding of the aetiology and pathogenesis of the two most prevalent and debilitating infectious diseases of koalas to make improved decisions regarding therapeutic intervention, prevention and management. Chlamydiosis, caused by two chlamydial bacteria, affects koala fertility, urinary tract function and eyesight. Cryptococcosis, caused by the fungus Cryptococcus gattii, may result in koala morbidity and death. Planned therapeutic trials, prevention strategies and the development of optimal husbandry strategies will provide knowledge that will lead to reduced koala morbidity through improved understanding of the interactions amongst infectious pathogens, the animal host and the environment.Read moreRead less
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
Establishment of Therapeutically Relevant Animal Models and Markers for Crohn's Disease. Crohn's disease is a devastating life long disease, affecting 0.5% of the world population. There is urgent economic and social need to develop new and better drugs to treat the symptoms and underlying cause of this debilitating disease. Social benefits include the improved quality of life of sufferers that positively impacts society. Economic benefit includes income derived from commercialisation of rese ....Establishment of Therapeutically Relevant Animal Models and Markers for Crohn's Disease. Crohn's disease is a devastating life long disease, affecting 0.5% of the world population. There is urgent economic and social need to develop new and better drugs to treat the symptoms and underlying cause of this debilitating disease. Social benefits include the improved quality of life of sufferers that positively impacts society. Economic benefit includes income derived from commercialisation of research outcomes and the contribution this project makes to high value employment in the biotechnology sector.Read moreRead less
Metal-Based Anti-inflammatory Drugs with High Efficacy and Low Side-Effects. Non-steroidal anti-inflammatory drugs (NSAIDs) have widespread human and veterinary applications for the treatment of arthritis and other inflammatory diseases, but their utility is limited by often severe gastrointestinal, renal and cardiac side-effects. The recently heralded COX-2 inhibitors have not lived up to their expectations in terms of efficacy and side-effects, therefore, there is a need to develop new potent ....Metal-Based Anti-inflammatory Drugs with High Efficacy and Low Side-Effects. Non-steroidal anti-inflammatory drugs (NSAIDs) have widespread human and veterinary applications for the treatment of arthritis and other inflammatory diseases, but their utility is limited by often severe gastrointestinal, renal and cardiac side-effects. The recently heralded COX-2 inhibitors have not lived up to their expectations in terms of efficacy and side-effects, therefore, there is a need to develop new potent, but safer, NSAIDs. This project is aimed at using the results from new lead compounds to design NSAIDs with much greater efficacy and much less side effects than those currently available.Read moreRead less