The Program Project, now in its fifteenth year, is a collaborative effort of colleagues interactions to apply modern methods of cellular, subcellular, and cell biology, and biochemistry to the study of respiratory function. The theme is the cellular and molecular biology of the alveolar epithelium with emphasis on the lung surfactant system. Primary topics include the synthesis and processing of surfactant associated proteins, the mechanisms for exocytosis of the lamellar bodies including the role of fusinogenic proteins and limited proteolysis, the mechanisms for reuptake of lung surfactant from the alveolar space including consideration of intracellular processing and reutilization of components, and mechanisms for transport of substrate (choline) into the cell for phospholipid synthesis. These projects are formulated around the central hypothesis that surfactant synthesis, secretion, and reuptake are linked in a regulated, granular pneumocyte-based lung surfactant cycle. Of the proposed projects, two are continuation efforts, another is a new project led by an investigator who has engaged in cooperative research during the previous period of grant support, and the fourth is the addition of a funded R0-1 currently in year 09. The four proposed projects are supported by a Cell Culture core which will provide cells for individual research projects, by an Imaging and Morphology core which will provide support for fluorescence imaging, immunocytochemistry and electron microscopy, and by an Administrative Unit for fiscal and secretarial management and support. In addition, the scientific core units will undertake methodology development in order to improve the delivery of core services - the Cell Culture core will standardize techniques for granular pneumocyte primary culture and the Imaging and Morphology core will develop reliable methods for localization and visualization of intracellular lipid. Information obtained in this program will contribute to basic understanding of the function of the lung surfactant system and provide important insights into the cellular and molecular basis of respiratory function.
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