Developmental Functions Of A Novel Zinc-finger Protein
Funder
National Health and Medical Research Council
Funding Amount
$666,812.00
Summary
Diseases of the respiratory track and the immune system represent major public health burdens, from the common cold and lung cancer, to increased risk of infections and auto-immune diseases. We have identified a new gene that is essential for lung development, and required for normal development of antibody-producing immune cells. Here we want to define the mechanism by which this gene functions, in order to better understand how lungs and immune cells develop.
The study of growth factors essential in normal kidney and lung development allows for the advancement of innovative therapies to promote postnatal growth and repair. A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of colony stimulating factor (CSF-1), a growth factor important for fetal growth during pregnancy. We have evidence that CSF-1 therapy can promote lungs to continue development and maturation aft ....The study of growth factors essential in normal kidney and lung development allows for the advancement of innovative therapies to promote postnatal growth and repair. A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of colony stimulating factor (CSF-1), a growth factor important for fetal growth during pregnancy. We have evidence that CSF-1 therapy can promote lungs to continue development and maturation after birth.Read moreRead less
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.
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
The Role Of Glucocorticoids, Retinol And CAMP Signaling In Lung Development And Neonatal Respiratory Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$447,000.00
Summary
Underdeveloped lungs at birth and adult lung diseases (ie emphysema, acute resipratory distress, and asthma) are a major cause of hopitalization and death. The World Health Organization ranks resipratory diseases at number 6 in the global burden of disease. Preterm birth with associated respiratory complications occurs in about 10% of all human births and accounts for 75% of neonatal deaths not associated with congenital abnormalities . Respiratory Distress Syndrome (RDS) is a major complication ....Underdeveloped lungs at birth and adult lung diseases (ie emphysema, acute resipratory distress, and asthma) are a major cause of hopitalization and death. The World Health Organization ranks resipratory diseases at number 6 in the global burden of disease. Preterm birth with associated respiratory complications occurs in about 10% of all human births and accounts for 75% of neonatal deaths not associated with congenital abnormalities . Respiratory Distress Syndrome (RDS) is a major complication in preterm births and the routine antenatal treatment of glucocorticoids has a major benefit in reducing incidence of RDS leading to decreased neonatal mortality. Glucocorticoids improve lung maturation yet their exact detailed role is not fully understood. Other systemic hormones and factors , such as vitamin A (precursor for retinoic acid) are also important in regulating, completing and maintaining proper lung development and function. Vitamin A deficiency alters lung structure and function, and is believed to be a causal factor in chronic lung diseases such as bronchopulmonary dysplasia, frequently problematic to infants. Detailed understanding of how these hormones work in the lung is critical to the future improvement of treatments for respiratory distress at birth and other respiratory conditions (emphysema, asthma) during adult life. We have developed a number of mouse models to study how these hormones work in the lung and allows us to perform investigations not possible in the human system. Using these mouse models of hormone resistance for glucocorticoids, retinoic acid (vitamin A) and cAMP signaling we will study in detail how these hormones work in the developing lung. Outcomes will be detailed knowledge and mechanisms of action that are critical for the design and testing of novel agents and therapies for immature lungs at birth and in adult lung dysfunction and diseaseRead moreRead less
Early Life Arsenic Exposure Alters Lung Development And Inflammatory Responses To Virus And Cigarette Smoke
Funder
National Health and Medical Research Council
Funding Amount
$455,380.00
Summary
The contamination of drinking water sources with arsenic is a global health issue affecting millions. While arsenic is a well known cancer causing agent, recent evidence suggests that early life arsenic exposure via drinking water increases the risk of obstructive lung disease in later life. This project aims to examine how the timing and dose of arsenic exposure influences lung development and the response to respiratory insults including viral infection and cigarette smoke.
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