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
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
This work will analyse how cells, the building blocks of tissues, are organized together to form functioning organs. It focuses on the adhesion molecules that allow cells to recognize one another, which cooperate with the internal skeleton of cells to link them together. We aim to understand how these cellular systems work normally and how they are targeted to disrupt tissue integrity in diseases like cancer and inflammation.
Effect Of Prostaglandin E2 On The Periodontium And Alveolar Bone Formation
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Dental disease affecting the supporting structures of teeth (the periodontium), is prevalent in our society. Periodontal disease results in destruction of bone around teeth, loosening of teeth, compromised chewing function, and tooth loss. Over the last twenty years reports into the effects of prostaglandin E2 (PGE2) on the skeleton have been divided and controversial. While historically PGE2 has been reported to promote bone resorption, more recently it has been demonstrated that when PGE is pl ....Dental disease affecting the supporting structures of teeth (the periodontium), is prevalent in our society. Periodontal disease results in destruction of bone around teeth, loosening of teeth, compromised chewing function, and tooth loss. Over the last twenty years reports into the effects of prostaglandin E2 (PGE2) on the skeleton have been divided and controversial. While historically PGE2 has been reported to promote bone resorption, more recently it has been demonstrated that when PGE is placed in contact with mandibular bone, adjacent to erupted teeth, new bone and cementum formation occurs. The ability of PGE2 to induce new bone formation indicates a potential use for PGE2 in the management of bone loss associated with periodontal diseases, and the formation of new bone around dental implants, and around teeth following orthodontic movement. Growth factors are active in healing and have valuable applications in augmenting wound repair. Osseous and dental tissues are rich in growth factors, and these factors are involved with the regulation of bone metabolism as well as tissue repair, thus the action of PGE2 on the periodontium is most likely regulated via these factors. Since regeneration of the periodontium is a fundamental goal of dentistry, any treatment which leads to predictable formation of new connective tissues and their long term stability would be a major clinical advance.Read moreRead less
Cortactin: Molecular Regulation Of Cadherin Activity And Epithelial Morphogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Interactions between cells and their neighbouring cells control many important processes in the body. The adhesion molecule E-cadherin is a major protein that controls how cells interact with one another in many epithelial tissues (e.g. breast, lung, gut). These tissues are the source of many common diseases, particular cancer and inflammation. E-cadherin is essential for these tissues to form normally, and loss of E-cadherin function contributes to disease in these tissues (especially common ca ....Interactions between cells and their neighbouring cells control many important processes in the body. The adhesion molecule E-cadherin is a major protein that controls how cells interact with one another in many epithelial tissues (e.g. breast, lung, gut). These tissues are the source of many common diseases, particular cancer and inflammation. E-cadherin is essential for these tissues to form normally, and loss of E-cadherin function contributes to disease in these tissues (especially common cancers, such as breast and lung). Understanding how E-cadherin controls normal cell function in these tissues will therefore provide key insights into how disease arises. In this study we will investigate how a protein which binds to E-cadherin, cortactin, contributes to the biological effect of E-cadherin in supporting tissue architecture. Understanding the fundamental elements of how cortactin works with E-cadherin will provide invaluable information into how cells recognize one another in health, and fail to adequately recognize each other in common diseases.Read moreRead less
MicroRNAs are small molecules that modulate the expression of most genes and so affect nearly every biological process and pathology although, they were only discovered in humans less than 10 years ago. The bottleneck in discovering the functions of miRNAs is in identifying their molecular targets, the majority of which remain unknown. We aim to comprehensively identify direct target genes of epithelial-specific microRNAs and to confirm a number of them by gene target validation approaches.