This research investigates the factors regulating the transition of the lung from the fluid filled organ in fetal life to the air filled organ required at birth. Many preterm babies fail this transition and in order to survive, their lungs often require mechanical ventilation, which has been suggested to cause lung injury. Using synchrotron generated X-rays, we can determine how particular resuscitation techniques are able to reduce this injury and promote aeration at birth.
Control Of Alveolar Epithelial Cell Differentiation Before And After Birth
Funder
National Health and Medical Research Council
Funding Amount
$376,980.00
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, which are essential for the normal functioning of the lung. Although both cell types look completely different and have very different functions, they are derived from the same precursor cell. However, it is not known what determines whether these cells will become a type-I or a type-II cell. This application ....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, which are essential for the normal functioning of the lung. Although both cell types look completely different and have very different functions, they are derived from the same precursor cell. However, it is not known what determines whether these cells will become a type-I or a type-II cell. This application is directed towards understanding the mechanisms which determine the fate of these cells. This is critical information as the lung must have the correct proportions of both cell types to function properly as a gas exchange organ.Read moreRead less
Physical Determinants Of Lung Development Before And After Birth
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Survival at birth is critically dependent upon the ability of the lungs to take on the role of exchanging gases; a role previously performed by the placenta. The lungs must, therefore, have grown and matured sufficiently during fetal life, before they are required at the time of birth. Inadequate development of the lungs during fetal life is the most common cause of death and disease in newborn babies. This may be due to premature birth, when the lungs have had insufficient time to develop, or i ....Survival at birth is critically dependent upon the ability of the lungs to take on the role of exchanging gases; a role previously performed by the placenta. The lungs must, therefore, have grown and matured sufficiently during fetal life, before they are required at the time of birth. Inadequate development of the lungs during fetal life is the most common cause of death and disease in newborn babies. This may be due to premature birth, when the lungs have had insufficient time to develop, or it may be due to inappropriate lung development during fetal life. It is important therefore, to understand the mechanisms that control growth and development of the lung both before and after birth. During fetal life the lungs are filled with liquid which expands the lungs and provides a stretch stimulus causing them to grow. Previously we have shown that a reduction in the degree of fetal lung expansion causes lung growth to cease. Likewise, if we increase the degree of lung expansion in the fetus, we induce a rapid increase in fetal lung growth and maturation. This stimulus is so potent that it can reverse an existing lung growth deficit, thus enabling survival of the newborn. In this application we will investigate the mechanisms by which alterations in lung expansion induce growth and maturation of the lung. Specifically we will investigate the role of calmodulin in fetal lung growth, because the genes that encode it are activated when the lung cells are growing most rapidly. In addition, we will identify other genes that are turned on or off during rapid growth of the lung because those genes are likely to play important roles in the regulation of fetal lung growth and development. We will also investigate the underlying differences in the control of lung growth at different stages of gestation, as well as investigate factors that regulate lung growth after birth, particularly in prematurely born animals.Read moreRead less
The Fetal Response To Infection, With Particular Reference To Alterations Of Tryptophan Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$410,616.00
Summary
Infection in pregnancy has long been known to be associated with a high risk for brain damage in the baby. There is now good evidence that the brain can be damaged before birth, and in other babies where the brain is damaged after birth there is reason to say that these infants were factors associated with the pregnancy that rendered them vulnerable to risk factors postnatally. Very little is known about the effects of infection on the fetus. Some recent work has shown that substances released f ....Infection in pregnancy has long been known to be associated with a high risk for brain damage in the baby. There is now good evidence that the brain can be damaged before birth, and in other babies where the brain is damaged after birth there is reason to say that these infants were factors associated with the pregnancy that rendered them vulnerable to risk factors postnatally. Very little is known about the effects of infection on the fetus. Some recent work has shown that substances released from bacteria induce cells in the uterus and placenta to produce inflammatory chemicals that can damage the brain. In this project we propose the following model: 1), infection causes the release of substances from the uterus and placenta that disrupt the blood-brain barrier in the fetal brain; and, 2), infection alters the metabolism of the essential amino acid tryptophan in the fetus, causing greater production of metabolites that have toxic effects on the developing brain. We have preliminary evidence to support these two proposals. If the idea is proven correct, it should be possible to administer simple analogues of tryptophan to prevent the toxic metabolites of this amino acid from increasing in the fetus when either the mother or the uterus becomes infected. Because these substances can be given by mouth, this would allow a simple treatment to be developed for women at risk of infection, or who are already infected. This would be particularly useful wherever medical services and resources are limited, as for under-priviledged groups and in Third World countries.Read moreRead less