Bronchopulmonary Dysplasia – A Regenerative Medicine Approach
Funder
National Health and Medical Research Council
Funding Amount
$480,406.00
Summary
Bronchopulmonary dysplasia is a major leading cause of morbidity and mortality in premature babies. There is no cure. We have previously shown that amnion epithelial cells can reduce the extent of lung damage during early stages of lung development. We aim to understand how amnion cells can promote repair by interacting with existing cell types in order to restore normal lung structure and function. The outcomes from this study will help design clinical trials and develop new therapies.
Second Trimester Intra-amniotic Treatment For Early Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$392,420.00
Summary
Preterm birth is the leading cause of neonatal death and disability in Australia today, with those born before 32 weeks' completed gestation at the highest risk. Preventing these early preterm births requires treatment of the causative uterine infection. This proposal is to conduct the first study of direct intraamniotic antibiotic treatment of uterine Ureaplasma infection in a clinically relevant, large animal model of second trimester pregnancy.
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.
Regulation Of Progesterone Action In Human Parturition.
Funder
National Health and Medical Research Council
Funding Amount
$314,983.00
Summary
Premature birth is the leading cause of neonatal death and sickness, and numbers are increasing due to our ignorance of the biology of labour. Progesterone maintains pregnancy and its withdrawal results in birth, but how this is achieved in humans is unknown. This project will determine the molecular mechanisms by which progesterone action is regulated during the transition from pregnancy to birth. This data will guide new strategies to prevent premature birth.
Novel Methods For Early Bedside Detection And Prognosis Of Preterm Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$630,880.00
Summary
Quick and robust assessments of preterm brain activity are critical for identifying early markers of brain injuries. We need to predict poor outcomes before they develop in order to give clinicians the best chance of helping sick infants. This project will develop and validate new non-invasive methods for assessing early brain activity in preterm infants at risk of developing poor neurodevelopmental outcomes.
Regulation Of Prostaglandin Endoperoxide Synthase-2 In The Human Fetal Membranes At Birth
Funder
National Health and Medical Research Council
Funding Amount
$249,750.00
Summary
Preterm birth with the resulting immaturity of babies is the leading cause of death and disease among newborns. Early birth occurs in 6 to 11% of pregnancies, and its rate is slowly increasing in industrialized countries. We need a much better knowledge of the regulation of the parturition process to find ways to reverse this trend. Prostaglandins are hormonal substances that stimulate uterine contractions, cervical dilatation and membrane rupture. Intrauterine tissues produce prostaglandins, an ....Preterm birth with the resulting immaturity of babies is the leading cause of death and disease among newborns. Early birth occurs in 6 to 11% of pregnancies, and its rate is slowly increasing in industrialized countries. We need a much better knowledge of the regulation of the parturition process to find ways to reverse this trend. Prostaglandins are hormonal substances that stimulate uterine contractions, cervical dilatation and membrane rupture. Intrauterine tissues produce prostaglandins, and an increase of prostaglandin levels in the uterus is likely responsible for inducing labour both normally and preterm. We have previously identified an enzyme protein in the fetal membranes, called prostaglandin synthase-2, that has a key role in the synthesis of intrauterine prostaglandins during pregnancy. This enzyme is increasingly expressed before labour onset. In the present application, we propose studies to determine what causes the increased expression. We hypothesize that the gene encoding this enzyme is specifically activated in the fetal membranes in preparation for labour. We will define the mechanism of regulation by determining the activity of the gene in tissues from women who deliver either spontaneously or without labour at term and preterm. Further, we will determine the interaction of regulatory proteins with the prostaglandin synthase-2 gene in these pregnancies in order to understand the mechanisms of regulation at the molecular level. Finally, we will conduct cell culture studies to experimentally manipulate prostaglandin synthase-2 gene activity in fetal membrane cells. As an overall outcome of this work, new targets may be identified for drugs to disrupt prostaglandin synthase-2 gene activation specifically in the fetal membranes. The long term perspective is to block prostaglandin synthesis in the uterus in order to suppress preterm labour and prevent preterm birth.Read moreRead less
We aim to predict neurodevelopmental disability in babies born very preterm, earlier and more accurately than currently possible, by identifying structural and functional connectivity features that correlate with clinical measures of motor and neurodevelopmental functions. To do this we will use brain magnetic resonance imaging (MRI), dense array electroencephalography (EEG) and structured clinical neurodevelopmental assessments to provide a cutting edge view of the state of brain development.
Imaging Lung Aeration And Lung Motion Following Very Premature Birth
Funder
National Health and Medical Research Council
Funding Amount
$517,631.00
Summary
Using a synchrotron as an X-ray source, we will image the lungs as they aerate at birth and optimise ventilation strategies that improve lung aeration while minimising the risk of ventilation-induced lung injury.
The Cellular And Molecular Mechanisms In The Initaition Of Human Labour
Funder
National Health and Medical Research Council
Funding Amount
$460,904.00
Summary
Being born too early is the major cause of perinatal morbidity and mortality and accounts for the majority of neonatal deaths. The aim of this project is to gain a better understanding of the mechanisms involved in premature birth with a view to future development of clinically useful interventions to reduce the high rates of mortality and long-term disability.
Understanding The Physiological Advantage Behind Delayed Cord Clamping.
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
Surviving the transition to newborn life at birth is critically dependent upon a major re-organization of the infant’s circulation which is triggered by umbilical cord occlusion and the onset of air-breathing. This application is focused on investigating procedures that assist in stabilising the circulation during the newborn period and protect it from large swings in cardiac output and blood flow that have the potential to cause vascular-related injury in newborn infants.