Regulation of Alveolar Epithelial Cell Differentiation

描述(由申请人提供)： 该提案代表了计划项目的第二次竞争性续签 格兰特关注的是肺的发育生物学。前面的 批准期内共出版或印刷稿件24篇，提交稿件8篇 手稿。教职员工的互动性很强，许多论文都是合著的 由项目教员提供。赠款的主题仍然是定义 调控上皮细胞分化的分子机制。其中三个 续签的四个项目延续了上一批赠款期间的主题。 已经增加了一个新项目和几个新的教员。所有的项目 使用独特的试剂和我们开发的体外和体内模型 上一个授权期。该提案涵盖了以下方面的肺发育 肺芽起始部位上皮细胞的形态特征 早期1型细胞分化与肺泡形成 产后期。项目6探讨了监管机制， 未来的肺上皮细胞是特定的，初始的肺芽在 内胚层前肠。项目5检查了FGF10指导的过程 在胎肺中形成新的呼吸道分支。项目2 重点是肺上皮细胞对氧化应激的适应 出生与上皮细胞谷胱甘肽系统在 调节围产期的基因表达。项目1涉及 T1α，一种1型细胞特异性基因，它的调控及其在其中的作用 1型细胞分化和肺泡形成。它还检查了 T_1α定义骨髓干细胞群体的可能性 能够作为1型肺泡型细胞移植到发育中的肺中。那里 有三个核心：管理、结构和生物信息。后者是 与加州大学伯克利分校生物信息学项目相联系的新核心 工程学。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 建立上皮细胞基因调控通路的模型。虽然每个项目都有 其自身的侧重点、上皮细胞分化的主题不同 胎儿肺发育的各个阶段，研究人员的广泛互动， 共享试剂和体外和体内实验系统 凭借核心设施，打造一支独一无二的互动、高效的团队 肺细胞和分子生物学家以及生物信息学工程师。

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.