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 Labour commenced ONLY AFTER the drug was withdrawn from the mother.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
Understanding The Regulation Of HERG Potassium Channel In The Myometrium At The Time Of Labour
Funder
National Health and Medical Research Council
Funding Amount
$597,661.00
Summary
We have shown that a potassium channel known as hERG falls precipitously at the time of term labour and that blocking this channel causes powerful uterine contractions. This grant will determine how the expression of this channel is regulated in the myometrium and whether changes in hERG channels also occur in premature labour.
Understanding The Myometrial Transition At Term And Preterm Labour To Guide Tocolysis
Funder
National Health and Medical Research Council
Funding Amount
$808,447.00
Summary
This grant seeks to understand how the muscle cells of the uterus transform at the time of labour. We propose that this transformation is organised by enzymes that modify the histones around key genes. We will test if a similar pathway operates in cases of preterm labour. The results will guide the development of new ways of treating premature labour that will use targeted nanoparticles to deliver siRNA directly to the muscle cells of the uterus.
Optimising Future Human Health By Optimising Birth Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$876,005.00
Summary
Laureate Professor Smith received an AM for his research on human pregnancy and contributions to Indigenous maternal health. His research has dramatically expanded in the last 5 years to include stillbirth, viral infections during pregnancy, early detection of renal disease, the development of targeted nanoparticles for delivery of therapeutics to the uterus, and data-linkage to test the impact of antenatal care. His research seeks to optimise the health of pregnant women and their children.
This project will test if the ratio of the two different estrogens found in the blood of pregnant women is the critical factor in determining the onset of contractions in the uterus at labour. The studies will also determine the role of a newly discovered receptor for estrogens in allowing powerful contractions at labour. Results will allow development of new treatments to prevent premature birth that block the actions of estrogen at this new receptor or change the ratio of the two estrogens.
Achieving Targeted Delivery Of Drugs To Uterine Muscle In Women For The Prevention Of Preterm Labour
Funder
National Health and Medical Research Council
Funding Amount
$469,008.00
Summary
We have patented liposomes targeted to the uterus, which enable us to deliver drugs specifically to the muscle cells of the uterus, increasing safety. The liposomes can be loaded with drugs that either block or promote contractions, creating a versatile drug delivery system that could treat premature labour or postpartum haemorrhage which are major clinical problems. We seek support to demonstrate their effectiveness in mouse and primate models of preterm labour prior to human studies.
Managing an ageing population for income adequacy and fiscal sustainability. This project aims to improve understanding of the impacts of existing key reforms intended to ease fiscal pressures associated with population ageing. The right mix of retirement income policies is vital to Australia's fiscal sustainability, however the effectiveness of existing policies is unknown. The project expects to identify impacts of key reforms on employment, re-training, income, savings and future retirement i ....Managing an ageing population for income adequacy and fiscal sustainability. This project aims to improve understanding of the impacts of existing key reforms intended to ease fiscal pressures associated with population ageing. The right mix of retirement income policies is vital to Australia's fiscal sustainability, however the effectiveness of existing policies is unknown. The project expects to identify impacts of key reforms on employment, re-training, income, savings and future retirement income and public pension receipt. The project will develop a new tax records-based dataset to facilitate future research on tax and welfare systems.Read moreRead less
Regional Australia' skills shortages and high-skill refugees' employment . Regional Australia loses to cities thousands of professional and trade-related people whose skills cannot be replaced. Focusing on small and medium-size enterprises producing food and beverages, this project aims to determine whether refugee employment (i) is a strategic resource (ii) can alleviate these chronic regional skill shortages, and (iii) can be integrated in immigration policy. In doing so, it will for the firs ....Regional Australia' skills shortages and high-skill refugees' employment . Regional Australia loses to cities thousands of professional and trade-related people whose skills cannot be replaced. Focusing on small and medium-size enterprises producing food and beverages, this project aims to determine whether refugee employment (i) is a strategic resource (ii) can alleviate these chronic regional skill shortages, and (iii) can be integrated in immigration policy. In doing so, it will for the first time provide critical empirical evidence on the possible need to separate policy measures aimed at rural vs. urban employers. The outcomes will contribute to reducing the problem of critical skill shortages and wastage at once and do so with an eye to the needs to rural Australia – a key driver of the country’s exports. Read moreRead less
Insecure Work and the Mental Health of Workers and their Families. This project aims to explore the relationship between insecure work and mental health by applying advanced econometric methods to large survey and administrative datasets, and newly collected survey data. This project expects to provide causal policy-relevant estimates of how insecure work is affecting the wellbeing of workers and their families, and for whom the effects are most harmful. It also expects to inform on how poor men ....Insecure Work and the Mental Health of Workers and their Families. This project aims to explore the relationship between insecure work and mental health by applying advanced econometric methods to large survey and administrative datasets, and newly collected survey data. This project expects to provide causal policy-relevant estimates of how insecure work is affecting the wellbeing of workers and their families, and for whom the effects are most harmful. It also expects to inform on how poor mental health influences the types of jobs that people enter into. This should provide significant benefits, including evidence needed to improve existing workplace and employment programs, and evidence ensuring that assistance is efficiently targeted to those workers and industries with the greatest need.Read moreRead less
Living on the Margin: The Relationship between Mental Health and Work in Australia. This project will assess the relationship between Australians' mental health and their work, for example, employment status, work conditions and hours. The study is the first to exploit the detailed timing of mental health and employment transitions to identify whether poor labour market outcomes lead to poor mental health or whether the reverse is true. New Australian data will be used to understand whether the ....Living on the Margin: The Relationship between Mental Health and Work in Australia. This project will assess the relationship between Australians' mental health and their work, for example, employment status, work conditions and hours. The study is the first to exploit the detailed timing of mental health and employment transitions to identify whether poor labour market outcomes lead to poor mental health or whether the reverse is true. New Australian data will be used to understand whether the link between mental health and work adds to the economic vulnerability of families and those at risk of homelessness. The results will advance our understanding of the way that mental health affects overall economic well-being and will inform current policy initiatives to promote economic participation and good mental health.Read moreRead less