Understanding And Preventing Adverse Developmental Effects Of Perinatal Infection/inflammation
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
Exposure of babies to infection or inflammation within the womb is common and is associated with preterm delivery and illness in newborns. The biggest problem for these babies is lung disease due to inflammation of the lungs before birth and/or in response to lung injury after birth. We are investigating how inflammation alters lung development, and working on developing a novel cell therapy to prevent life-threatening newborn lung disease.
Novel Therapy For Enhancing Organ Maturation In Pre-term Babies
Funder
National Health and Medical Research Council
Funding Amount
$694,323.00
Summary
This project is developing a factor to enhance organ maturation and repair that may provide a new therapy for premature babies and fetuses with birth defects. This exciting new finding allows for the development of treatments of underdeveloped organs, in particular the lungs of premature and growth restricted babies. We are also trialing this factor in unborn babies with defects to the kidneys and lungs of which there is currently no cure.
The survival of a baby at birth is crtically dependent upon the ability of the lungs to successfully take over the role of exchanging oxygen and carbon dioxide between the air and blood. To perform this task, during fetal life the lung must have grown properly and near the end of gestation it must mature both structurally and biochemically. Thus, babies that are born early, before the expected time of birth, are born before the lungs have had the opportunity to mature. It is not surprising, ther ....The survival of a baby at birth is crtically dependent upon the ability of the lungs to successfully take over the role of exchanging oxygen and carbon dioxide between the air and blood. To perform this task, during fetal life the lung must have grown properly and near the end of gestation it must mature both structurally and biochemically. Thus, babies that are born early, before the expected time of birth, are born before the lungs have had the opportunity to mature. It is not surprising, therefore, that an inability to breathe is one of the primary problems faced by a prematurely born infant. During late gestation the lung changes dramatically in order to increase its ability to exchange gases. There is an increase in surface area and a reduction in the barrier thickness between the airspace and the blood stream. The molecular mechanisms involved in this remodelling are unknown, but it is known that the administration of corticosteroids to women at risk of preterm labour causes a large decrease in this barrier thickness and increases the distensibility of the lung. This project seeks to understand how the structure of the lung matures in late gestation and to determine whether corticosteroids regulate these changes by altering the structure of a specialised molecule, called versican. Versican resides in the tissue space outside of cells and has special properties that allow it to retain water and help organise the surrounding matrix. We propose that alterations in the structure of versican will reduce its ability to retain water, thereby reducing the tissue volume and contributing to a reduction in the air-blood tissue barrier within the lung.Read moreRead less
Improving The Fetal To Neonatal Transition In Compromised Newborns; Towards Better Outcomes For Babies Born Too Soon Or With Under-developed Lungs
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
The birth of a compromised infant affects 13 million pregnancies worldwide annually and is the greatest cause of neonatal death, disability and chronic disease. I will identify mechanisms to greatly improve the fetal to neonatal transition in premature babies and babies with under-developed lungs. This research is urgently required to provide the necessary evidence to target interventions in the delivery room to reduce the short- and long-term burden of disease in compromised newborns.
Alveolar Epithelial Cell Differentiation And Apoptosis: Effects Of Preterm Birth, Corticosteroids And Stretch.
Funder
National Health and Medical Research Council
Funding Amount
$484,500.00
Summary
In the lung, gas exchange takes place in small terminal airsacs called alveoli. The internal surface of the alveoli are lined with 2 types of specialist cells, the type-I and type-II cells. Both cells are essential for the normal functioning of the lung; type-I cells provide a thin barrier for the gas exchange, whereas type-II cells produce the surface-active material, surfactant. In order to survive after birth, the lungs of the newborn must have appropriate numbers of each of these cell types. ....In the lung, gas exchange takes place in small terminal airsacs called alveoli. The internal surface of the alveoli are lined with 2 types of specialist cells, the type-I and type-II cells. Both cells are essential for the normal functioning of the lung; type-I cells provide a thin barrier for the gas exchange, whereas type-II cells produce the surface-active material, surfactant. In order to survive after birth, the lungs of the newborn must have appropriate numbers of each of these cell types. However, babies that are born very prematurely have few, if any, mature cells as most are non-specialised cells that possess none of the characteristics of mature type-I and type-II cells. Therefore, the lungs of very preterm babies have low levels of surfactant, are prone to injury and infection and are not efficient in the exchange of oxygen and carbon dioxide. As such, these infants are at high risk of developing chronic lung disease which is a serious debilitating disease that has long term health implications. We believe that the non-specialised cells are more prone to injury and cell death than mature cells which makes the very premature infant more susceptible to the development of chronic lung disease. As the survival and respiratory health of these infants depends upon most type-I and type-II cells maturing after birth, it is critical to understand the factors that regulate their maturation. This information will allow the development of treatments that can enhance the maturation of these cell types. This application is focused towards understanding the factors that control maturation of type-I and type-II cells, as well as the role of the non-specialised cells in the development of chronic lung disease in babies that are born very prematurely.Read moreRead less
Fetal Responses To Intra-uterine Inflammation And The Postnatal Pulmonary Consequences
Funder
National Health and Medical Research Council
Funding Amount
$347,036.00
Summary
There is increasing evidence that exposure of the unborn baby to infection and inflammation may be the cause of several important and disabling illnesses in later life, including long-term lung injury and brain damage. Hospital-based studies have shown that infants who go on to develop these diseases have signs of inflammation before, and soon after, birth. These studies in humans, however, have only shown associations between inflammation and later disease. Carefully controlled scientific exper ....There is increasing evidence that exposure of the unborn baby to infection and inflammation may be the cause of several important and disabling illnesses in later life, including long-term lung injury and brain damage. Hospital-based studies have shown that infants who go on to develop these diseases have signs of inflammation before, and soon after, birth. These studies in humans, however, have only shown associations between inflammation and later disease. Carefully controlled scientific experiments are required to show that inflammation actually causes damage and to allow us to find ways to prevent or cure the diseases that result from such injury. In 1998, using sheep, our research group discovered a way to produce inflammation in the fetus without endangering its wellbeing or causing early labour. The inflammation is caused by injecting a sterile bacterial cell wall preparation (endotoxin) into the amniotic fluid surrounding the fetus. Using this model, we have found that an episode of inflammation before birth profoundly increases lung maturity, thus increasing the chances of survival if premature birth occurs. Based on our information from humans, we expect that if these lambs are allowed to survive past the first few days after birth, they will go on to develop chronic lung disease, and perhaps brain damage. This study will answer vital questions about the events that occur in the uterus and the fetus during periods of inflammation, and will then determine the long-term consequences in the weeks following birth. We expect that these lambs will have changes which at first will increase their chances of survival after birth, to be followed by chronic disability due to lung and brain damage. If confirmed, this finding will allow us to find treatments which can be applied before birth to ensure that children are less likely to be born with these disabling illnesses.Read moreRead less