Regulation of Alveolar Epithelial Cell Differentiation

描述（由申请人提供）： 本建议书是计划项目的第二次竞争性更新 格兰特关注的是肺的发育生物学。前述 赠款期内出版或付印了24份手稿，提交了8份 手稿教师是高度互动的，许多论文已合著 项目教师。赠款的主题仍然是定义 调节上皮细胞分化的分子机制。三 更新的四个项目延续了上一个赠款期的主题。 增加了一个新项目和几个新的教师。的所有项目 使用独特的试剂以及我们在研究期间开发的体外和体内模型， 上一个补助期。该提案涵盖了肺的发展， 原始肺芽上皮细胞的特化 早期1型细胞分化和肺泡形成 产后时期项目6探讨监管机制， 未来的肺上皮细胞被指定，最初的肺芽形成于 内胚层前肠项目5研究了FGF 10指导的过程， 上皮细胞在胎儿肺中形成新的气道分支。计划2 着重于肺上皮细胞对氧化应激的适应， 以及上皮细胞谷胱甘肽系统在 在围产期调节基因表达。项目1涉及 T1 α，一种1型细胞特异性基因，其调控及其在细胞凋亡中的作用 1型细胞分化和肺泡形成。它还审查了 T1 α定义骨髓干细胞群体的可能性 能够作为肺泡1型细胞移植到发育中的肺中。那里 有三个核心：行政，结构和生物信息。后者是 一个新的核心链接到BU生物信息学计划在学院 工程.它提供基因表达阵列，生物信息学专业知识， 解释基因表达的复杂模式，QRT-PCR和新方法 上皮细胞基因调控途径的建模。虽然每个项目 其本身的重点，主题上皮细胞分化在不同的 胎儿肺发育的阶段，研究者的广泛互动， 共享的试剂以及体外和体内实验系统， 与核心设施，创造一个独特的互动和生产力的团队， 肺细胞和分子生物学家和生物信息学工程师。

DESCRIPTION (provided by applicant): This proposal represents the second competitive renewal of a Program Project Grant concerned with the developmental biology of the lung. The preceding grant period resulted in 24 manuscripts published or in press and 8 submitted manuscripts. The faculty is highly interactive, and many papers have been coauthored by project faculty. The theme of the grant remains the definition of molecular mechanisms regulating epithelial cell differentiation. Three of the four projects of the renewal continue themes from the previous grant period. One new project and several new faculty have been added. All of the projects use unique reagents and in vitro and in vivo models we have developed during the previous grant period. The proposal covers lung development from specification of epithelial cells of the initial lung bud through differentiation of type 1 cells and formation of lung alveoli in the early postnatal period. Project 6 explores the regulatory mechanisms by which the future lung epithelial cells are specified and the initial lung bud forms in the endodermal foregut. Project 5 examines the process by which FGF10 directs epithelial cells to form new airway branches in the fetal lung. Project 2 focuses on the adaptation of the lung epithelium to the oxidant stress at birth and the role that the epithelial cell glutathione system plays in regulating gene expression in the perinatal period. Project 1 deals with T1alpha, a type 1 cell-specific gene, its regulation and the role it plays in type 1 cell differentiation and alveolar formation. It also examines the possibility that T1alpha defines a population of bone marrow stem cells capable of engrafting as alveolar type 1 cells in the developing lung. There are three cores: administrative, structural and bioinformatic. The latter is a new core linked to the BU Bioinformatics Program in the College of Engineering. It provides gene expression arrays, bioinformatic expertise for interpreting complex patterns of gene expression, QRT-PCR, and new approaches to modeling epithelial cell gene regulatory pathways. While each project has its own focus, the theme of epithelial cell differentiation at different stages of fetal lung development, the extensive interactions of investigators, the shared reagents and in vitro and in vivo experimental systems, together with the core facilities, create a uniquely interactive and productive team of lung cell and molecular biologists and bioinformatics engineers.