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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
I am a developmental lung physiologist who specialises in understanding the factors regulating normal and abnormal lung development as well as the physiological transformation of the lung into an efficient gas-exchange organ at birth.
I am a developmental lung physiologist who specialises in understanding the factors regulating normal and abnormal lung development as well as the physiological transformation of the lung into an efficient gas-exchange organ at birth.
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
Improved Respiratory Support And Outcomes For Very Preterm Babies
Funder
National Health and Medical Research Council
Funding Amount
$9,185,907.00
Summary
Premature babies are born with lungs that are not developed enough to sustain their breathing needs after birth. As a result, they need intensive care which is the most costly and challenging problem in newborn medicine as these infants can suffer life-long diseases because of their early birth. This programs study will help to understand the causes of lung disease in premature babies and develop better ways of caring for them to improve their chances of survival without ongoing illness and disa ....Premature babies are born with lungs that are not developed enough to sustain their breathing needs after birth. As a result, they need intensive care which is the most costly and challenging problem in newborn medicine as these infants can suffer life-long diseases because of their early birth. This programs study will help to understand the causes of lung disease in premature babies and develop better ways of caring for them to improve their chances of survival without ongoing illness and disabilityRead moreRead less