Development and maintenance of the alveolar type 1 cell

描述（由申请人提供）： 这项新的研究者提案描述了一项为期5年的培训计划，旨在发展肺部医学领域的医生科学家职业生涯。主要研究者在波士顿大学完成了肺部和重症监护医学研究金，并在斯坦福大学生物化学系完成了为期一年的研究金，他现在继续担任医学系肺部和重症监护部门的讲师。在开展拟议的研究中，主要研究者将获得肺组织学、小鼠遗传学、分子生物学和基因组方法方面的专业知识。Mark A.博士克拉斯诺将指导首席研究员的科学发展。他是斯坦福大学生物化学教授和主席，也是霍华德休斯医学研究所的研究员，他培养了许多人，这些人后来建立了自己的实验室，并成功地获得了独立的资金。首席研究员还聘请了三位国际公认的权威，分别在肺上皮细胞生物学，肺泡发育和小鼠遗传学领域，作为顾问。他将与导师和顾问密切合作，以确保实现具体目标。一个由斯坦福大学高级研究人员组成的咨询委员会也已成立，将提供科学和职业建议。研究将集中在肺泡1型（AT1）细胞的发育和维持上.具体目标包括：1）使用分子标记物鉴定和表征小鼠肺中AT 1细胞的推定的双潜能祖细胞，并确定其何时何地产生，以及其在肺发育期间如何变化，2）使用小鼠转基因技术标记和追踪成熟AT 2细胞的命运，以确定AT 2细胞是否是AT 1细胞的专性祖细胞，3）通过RNA原位杂交技术筛选AT 1形态发生时在终末气腔上皮选择性表达的转录因子基因，以鉴定AT 1命运的潜在调控因子。通过汇集来自多个部门的独特资源，该计划整合了专业领域的专业知识，以确保实现特定目标。这项工作将是相关的理解和最终治疗肺气肿，肺癌和肺纤维化等肺部疾病。 (End摘要）

DESCRIPTION (provided by applicant): This new investigator proposal describes a 5 year training program for the development of a career as a Physician scientist in pulmonary medicine. The principal investigator has completed a fellowship in pulmonary and critical care medicine at Boston University and a one year research fellowship in the Department of Biochemistry at Stanford University, where he now continues as an Instructor in the Pulmonary and Critical Care division of the Department of Medicine. In carrying out the proposed research, the Principal Investigator will acquire expertise in lung histology, mouse genetics, molecular biology, and genomic approaches. Dr. Mark A. Krasnow will mentor the Principal Investigator's scientific development. He is Professor and Chairman of Biochemistry at Stanford and an Investigator in the Howard Hughes Medical Institute who has trained numerous individuals who have gone on to establish their own laboratories and successfully compete for independent funding. The Principal Investigator has also enlisted three internationally recognized authorities in the fields of lung epithelial cell biology, alveolar development and mouse genetics, respectively, as consultants. He will work closely with the mentor and consultants to ensure fulfillment of the specific aims. An advisory committee of senior investigators at Stanford has also been assembled and will provide scientific and career advice. Research will focus on development and maintenance of the alveolar type 1 (AT 1) cell. Specific aims include: 1) Identify and characterize using molecular markers the putative bi-potential progenitor of AT 1 cells in mouse lung and determine when and where it arises, and how it changes during lung development, 2) Use mouse transgenic techniques to label and trace the fate of mature AT 2 cells to determine whether the AT 2 cell is an obligate progenitor to the AT 1 cell, 3) To identify potential regulators of AT 1 fate by using RNA in situ hybridization to screen for transcription factor genes that are selectively expressed in terminal airspace epithelium at the time of AT 1 morphogenesis. By bringing together unique resources from multiple departments, this program integrates specialized areas of expertise that will ensure fulfillment of the specific aims. This work will be relevant for understanding and ultimately treating lung diseases like emphysema, lung cancer, and pulmonary fibrosis. (End of Abstract)