Antagonist Of Corticotrophin Releasing Hormone As Therapeutic Agents For The Prevention Of Premature Birth In Humans
Funder
National Health and Medical Research Council
Funding Amount
$376,650.00
Summary
In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow ....In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow the extension of pregnancy term The development of protocols that will in turn reduce neonatal mortality. Additionally we believe that these new agents will be useful in preventing the onset of labour after fetal surgery. Currently there are no effective treatments capable of substantially changing delivery dates. Available therapeutics delay the onset of labour, at best, 24 hours. However, recent exciting results from our laboratories show that rising concentrations of the placental peptide Corticotrophin Releasing Hormone (CRH) are associated with the onset of labour. Further, we have also delayed the onset of labour in pregnant sheep by infusing a relatively insoluble CRH antagonist into the sheep fetus. Labour commenced ONLY AFTER the drug was withdrawn from the mother. This project builds upon an interdisciplinary team: medicinal chemists, molecular modellers, pharmacologists and endocrinologists, to further develop an exciting Australian discovery. Successful completeion of this research will, for the first time, allow the control of pregnancy duration MAXIMISING the benefits to mother and child, reducing mortality and later life morbidities typically associated with premature birth.Read moreRead less
In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-ski ....In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-skilled techniques, including cryo-electron microscopy and single-molecule imaging and holds ancillary benefits to postgraduate students. Anticipated outcomes include influential publications, building a critical mass of expertise in Australia and fostering international collaborations with Australia at the epicentre.Read moreRead less
Biofocussed Prostate Cancer RadioTherapy (BiRT): A Personalised Approach To Delivering The Right Dose To The Right Place
Funder
National Health and Medical Research Council
Funding Amount
$753,565.00
Summary
We propose a new approach to treating prostate cancer with radiotherapy to move from the standard whole prostate treatment to a personalised treatment that varies radiation intensity throughout the prostate. We will mathematically combine features that influence radiotherapy effect from advanced imaging, clinical and biopsy information. This model will map out the radiotherapy dose required at each part of the prostate, to maximise killing of the cancer whilst minimising harm to normal tissue
Optimal management of corrosion and odour problems in sewer systems. Pollutants in wastewater undergo complex changes in sewers, leading to the production and release of odorous and corrosive compounds. Despite major efforts and expenditure by water utilities to mitigate these problems, odorous emissions from sewers are still commonly occurring in urban areas. Furthermore, the value of public assets is significantly diminished due to sewer corrosion, costing hundreds of millions of dollars a yea ....Optimal management of corrosion and odour problems in sewer systems. Pollutants in wastewater undergo complex changes in sewers, leading to the production and release of odorous and corrosive compounds. Despite major efforts and expenditure by water utilities to mitigate these problems, odorous emissions from sewers are still commonly occurring in urban areas. Furthermore, the value of public assets is significantly diminished due to sewer corrosion, costing hundreds of millions of dollars a year in Australia alone. This project is a major joint effort by the Australian water industry and world-leading scientists to generate advanced knowledge and develop effective technologies for optimal odour and corrosion management in sewers, delivering large social, environmental and economic benefits.Read moreRead less
Sewer corrosion reduction through model-supported ventilation control. Ventilation is one of the key technologies for sewer corrosion control. However, its design and operation are currently based on experience and empirical equations, often leading to unsatisfactory results. By integrating in-depth laboratory and pilot-sewer studies under defined conditions with extensive field investigations, this multidisciplinary project aims to develop critical models to predict the corrosion process in res ....Sewer corrosion reduction through model-supported ventilation control. Ventilation is one of the key technologies for sewer corrosion control. However, its design and operation are currently based on experience and empirical equations, often leading to unsatisfactory results. By integrating in-depth laboratory and pilot-sewer studies under defined conditions with extensive field investigations, this multidisciplinary project aims to develop critical models to predict the corrosion process in response to ventilation and dynamic wastewater and atmospheric conditions, enabling model-based sewer ventilation design and operation. The project also aims to deliver novel, field-demonstrated ventilation strategies. The project findings will be incorporated in the Australian ventilation design and operation guidelines.Read moreRead less
Experiment-numerical-virtual Generative Design for Nondeterministic Impacts. This project will establish an advanced nondeterministic design methodology to uncover the optimised material properties and 3D printed metastructural capacity in real-time against impact loading. It will develop a rigorous framework that integrates numerical simulation, experiment, and machine learning-based virtual modelling to tackle practical challenges in design and manufacture of impact-proof materials and structu ....Experiment-numerical-virtual Generative Design for Nondeterministic Impacts. This project will establish an advanced nondeterministic design methodology to uncover the optimised material properties and 3D printed metastructural capacity in real-time against impact loading. It will develop a rigorous framework that integrates numerical simulation, experiment, and machine learning-based virtual modelling to tackle practical challenges in design and manufacture of impact-proof materials and structures with intrinsic uncertainties. The generative design-calibration system unifying experimental-numerical-virtual processes will largely reduce the need for repetitive large-scale experimental tests. This project benefits civil, aerospace, automotive, and defence with competitive advantage through technological innovation.Read moreRead less
Microstructural-Functional Effect of Silver Diammine Fluoride on Apatites. This project aims to develop a fundamental understanding at the nanostructural level of the factors that contribute to the enhanced mineralisation and mechanical properties of dentine and enamel following the treatment with silver diammine fluoride (SDF). A variety of advanced nanomechanical, tomographic and microscopic techniques will be used to characterise sound, carious and SDF treated tissue. The new biomechanical ev ....Microstructural-Functional Effect of Silver Diammine Fluoride on Apatites. This project aims to develop a fundamental understanding at the nanostructural level of the factors that contribute to the enhanced mineralisation and mechanical properties of dentine and enamel following the treatment with silver diammine fluoride (SDF). A variety of advanced nanomechanical, tomographic and microscopic techniques will be used to characterise sound, carious and SDF treated tissue. The new biomechanical evidence on the underlying mechanisms, alternative protocols, delivery systems enable to optimise the treatment. The scientific insights into arresting/repairing damage processes will provide critical data for developing minimal intervention protocols for pediatric and geriatric populations.Read moreRead less
Defining Epigenetic Predictors Of Long-term Outcomes Of Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$409,408.00
Summary
On average, those born premature do worse health-wise than those born at term. However, some do worse than others. Our aim is to identify these people at birth to better help doctors and parents to closely monitor their health. For this, we will be “reading the diary of pregnancy” in the molecules added to chromosomes in blood during pregnancy in young adults with will characterised states of health. We will analyse DNA from blood that we will extract from stored heel prick spots.