The theme of this SCOR proposal is Normal and Disordered Growth and Development of Respiratory Systems. It represents a continuation of a Pediatric Pulmonary SCOR (now in year 14) which in the past has focused on lung infections and their consequences on airways growth and development. The proposal includes two projects which continue previous SCOR studies and 5 new projects which address in greater depth the molecular mechanisms of airways development, injury and repair, and regulation of airway tone. Four core services (Administrative, Molecular Biology, Morphology/Ultrastructure and Microbiology/Immunology) will support these projects. The first four projects constitute a subgroup which explores molecular aspects of ciliated (Project II) and secretory (Project III) cell differentiation in large airways, response of these cells to injury, and mechanisms which may play a role in development and repair of this epithelium, i.e., growth factors (Project I) and cell-cell communication through gap junctions (Project IV). These studies will rely heavily on the postnatal ferret trachea as a developmental and injury model, but will examine human tissue and use a range of experimental models from primary cultures of epithelial cells to transgenic animals that overexpress and underexpress IGF-I in order to probe the molecular events attending normal development and repair. Previous SCOR studies have identified the attachment protein (PI) of Mycoplasma pneumoniae and F glycoprotein of respiratory syncytial virus (RSV) as important immunogens. Project IV proposes to clone these genes into an adenovirus to produce a live oral vaccine for the prevention of mycoplasma infection. We anticipate that these coordinated and interactive studies will provide essential basic and applied information that will be used to 1) better understand the origins and course of childhood obstructive airways disease and apnea and 2) develop improved therapeutic and preventive approaches to these problems.
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