Bias and allostery at the calcium sensing receptor. This project aims to provide a mechanistic and dynamic picture of the structure, function and physiology of the human calcium sensing receptor (CaSR), which is critical for vertebrate life. By responding to chemicals in the body, it acts as a universal nutrient sensor to maintain extracellular calcium homeostasis and mediate biological functions, including neurotransmission, inflammation, digestion, blood pressure and development. However, it i ....Bias and allostery at the calcium sensing receptor. This project aims to provide a mechanistic and dynamic picture of the structure, function and physiology of the human calcium sensing receptor (CaSR), which is critical for vertebrate life. By responding to chemicals in the body, it acts as a universal nutrient sensor to maintain extracellular calcium homeostasis and mediate biological functions, including neurotransmission, inflammation, digestion, blood pressure and development. However, it is not known how this single receptor controls the actions of multiple ligands to mediate numerous functions. By elucidating the roles of the CaSR and its ligands, this project aims to better understand fundamental physiological processes.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
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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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883078
Funder
Australian Research Council
Funding Amount
$356,000.00
Summary
Liquid Chromatography Tandem Mass Spectrometry Steroid Analysis Facility. This first of a new generation of ultra-sensitive analytical mass spectrometers for small molecules will be established as a national assay facility allowing all Australian researchers open access to a new dimension of highly accurate and simultaneous measurements of multiple bodily chemicals such as steroids, vitamins and hormones. It is crucial to developing new knowledge in basic, developmental and pathological cell bio ....Liquid Chromatography Tandem Mass Spectrometry Steroid Analysis Facility. This first of a new generation of ultra-sensitive analytical mass spectrometers for small molecules will be established as a national assay facility allowing all Australian researchers open access to a new dimension of highly accurate and simultaneous measurements of multiple bodily chemicals such as steroids, vitamins and hormones. It is crucial to developing new knowledge in basic, developmental and pathological cell biology and for underpinning commercial developments of new molecular targets for therapeutic drugs for many diseases including cancer, cardiovascular disease and reproductive disorders. This facility is pivotal to maintaining international competitiveness in many areas of biological research in national priority areas.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC180100021
Funder
Australian Research Council
Funding Amount
$4,163,359.00
Summary
ARC Training Centre for the Development of Tools for Fragment Based Design. The ARC Training Centre for the Development of Tools for Fragment Based Design aims to inspire the next generation of drug discovery research leaders. It plans to provide direct experience with industry partners, training and master classes in early stage drug-discovery from industry experts. The Centre is expected to accelerate research translation and industry engagement by providing an efficient strategy for the scree ....ARC Training Centre for the Development of Tools for Fragment Based Design. The ARC Training Centre for the Development of Tools for Fragment Based Design aims to inspire the next generation of drug discovery research leaders. It plans to provide direct experience with industry partners, training and master classes in early stage drug-discovery from industry experts. The Centre is expected to accelerate research translation and industry engagement by providing an efficient strategy for the screening of a biological target and early medicinal chemistry for optimisation. The expected outcome of the Centre is to equip the trainees with the skills to make key contributions to the sustainability and growth of the sector and to provide significant capacity to address global challenges for 21st century pharmaceutical innovation.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668246
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Advanced Cell Labelling and Imaging Facility. Understanding the genetic regulation of cellular processes such as migration, differentiation and growth is an important frontier technology with significant biomedical potential. The Australian community is facing an increasing need to provide solutions for a variety of human diseases and disorders, including birth defects, nervous system injury and stroke, and ageing-related conditions. The proposed facility will allow researchers to test in vivo g ....Advanced Cell Labelling and Imaging Facility. Understanding the genetic regulation of cellular processes such as migration, differentiation and growth is an important frontier technology with significant biomedical potential. The Australian community is facing an increasing need to provide solutions for a variety of human diseases and disorders, including birth defects, nervous system injury and stroke, and ageing-related conditions. The proposed facility will allow researchers to test in vivo gene/pharmaceutical therapies as well as to better understand the genetic regulation of normal cellular processes. Read moreRead less
Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a gr ....Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668493
Funder
Australian Research Council
Funding Amount
$230,000.00
Summary
Characterising particulate laden flow in the lung airways: from drug delivery to primary anthropogenic sources. Facilities will provide infrastructure at Monash University and University of Sydney to continue the collaboration enhancing excellence in an exciting application of fluidics research, supporting the highest level of graduate training, providing innovative tools for industry and promoting industrial collaborations. The infrastructure is unique and will create international funding and ....Characterising particulate laden flow in the lung airways: from drug delivery to primary anthropogenic sources. Facilities will provide infrastructure at Monash University and University of Sydney to continue the collaboration enhancing excellence in an exciting application of fluidics research, supporting the highest level of graduate training, providing innovative tools for industry and promoting industrial collaborations. The infrastructure is unique and will create international funding and collaborative opportunities to support research and postgraduate training. The equipment will add value to existing infrastructure to enhance understanding of particulate flow with the paradoxical outcomes of improving drug deposition in respiratory delivery and of minimising anthropogenic particular deposition for better therapeutic and health outcomes.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560661
Funder
Australian Research Council
Funding Amount
$245,300.00
Summary
Particulate Characterisation for Pharmaceutical and Engineering Applications. The aim of this proposal is to establish joint facilities between the University of Sydney, Monash University and UNSW for the characterization of surface properties and particle sizes of pharmaceutical aerosols and industrial powders. Such knowledge is important for controlling aerosol production and delivery of drug particles to the lungs. This will have a significant benefit to the pharmaceutical industry and patien ....Particulate Characterisation for Pharmaceutical and Engineering Applications. The aim of this proposal is to establish joint facilities between the University of Sydney, Monash University and UNSW for the characterization of surface properties and particle sizes of pharmaceutical aerosols and industrial powders. Such knowledge is important for controlling aerosol production and delivery of drug particles to the lungs. This will have a significant benefit to the pharmaceutical industry and patients requiring aerosol treatment. Further, the proposed facilities will enhance research in complex particulate processes and modelling, functional nanomaterials, and soft sensor development, thus keeping Australia at the forefront of powder research into various high value adding particulate areas.Read moreRead less