NICOTINE AND NICOTINIC SIGNALING LUNG DEVELOPMENT

尼古丁和烟碱信号肺部发育

• 批准号: 6182752
• 负责人: CAROL W WUENSCHELL
• 金额: $ 6.91万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-05 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6182752
• 关键词: cell differentiation; embryo /fetus tissue /cell culture; embryo /fetus toxicology; gastrin releasing peptide; gene expression; growth factor receptors; histogenesis; in situ hybridization; laboratory mouse; lung; mammalian embryology; molecular cloning; neuropeptide receptor; nicotine; nicotinic receptors; polymerase chain reaction; pulmonary surfactants; receptor expression; respiratory epithelium

DESCRIPTION: (Adapted from applicant's abstract) The candidate's goal is to pursue an independent research career in the field of lung developmental biology. The candidate was trained as a developmental biologist at UCLA. Her graduate and postdoctoral training involved the use of a variety of molecular and genetic approaches to the study of gene expression in developing neurobiological systems. Her entry into the area of lung biology is relatively recent and represents a new direction for her career. The candidate holds a faculty appointment at the Center for Craniofacial Molecular Biology of the University of Southern California. This highly interactive, state-of-the-art research center has provided full support for the candidate's independent research efforts for the past two and a half years and is committed to her continued pursuit of a research career. The candidate plans to develop her career by acquiring new research skills and increasing her knowledge of lung biology and lung diseases through course work, and through formation of new collaborations and new contacts with clinicians and researchers at USC and elsewhere. The candidate is interested in understanding the mechanisms by which prenatal exposure to maternal smoking affects embryonic and fetal lung development, leading to the observed short and long term effects on the respiratory health of the offspring. Her Research Plan addresses the following hypothesis: Nicotine alters the developmental program of the embryonic lung (including expression of surfactant protein genes) through a mechanism involving nicotinic acetylcholine receptors located on cells of the distal epithelium and stimulation of production of GRP by these same distal epithelial cells. The Specific aims are: 1) to characterize the effect of added nicotine on the development of embryonic mouse lungs grown in serumless culture with respect to specific gene expression, growth, branching morphogenesis and differentiation of epithelial cell types, 2) to determine the nature and location of nicotinic acetylcholine receptors mediating the developmental effects of nicotine in the lung and 3) to test the role of the peptide growth factor GRP and its receptor in mediating the effects of nicotine in embryonic lung.

描述：（改编自申请人的摘要）候选人的目标是 在肺领域追求独立的研究生涯 发育生物学。 候选人接受过发展培训 加州大学洛杉矶分校的生物学家。 她的研究生和博士后培训涉及 使用各种分子和遗传学方法来研究基因 发育中的神经生物学系统中的表达。 她进入该地区 肺生物学的研究相对较新，代表了一个新的方向 她的职业生涯。 候选人在该中心担任教职 南加州大学颅面分子生物学。 这个高度互动、最先进的研究中心提供了 全力支持候选人过去的独立研究工作 两年半的时间里，她致力于继续追求 研究生涯。 该候选人计划通过收购来发展她的职业生涯 新的研究技能并增加了她对肺生物学和肺的了解 通过课程工作和建立新的合作来预防疾病 以及与南加州大学和其他地方的临床医生和研究人员的新联系。 候选人有兴趣了解其机制 产前接触母亲吸烟会影响胚胎和胎儿的肺部 的发展，导致观察到的短期和长期影响 后代的呼吸系统健康。 她的研究计划涉及 以下假设：尼古丁改变了大脑的发育程序 胚胎肺（包括表面活性蛋白基因的表达）通过 涉及细胞上烟碱乙酰胆碱受体的机制 远端上皮的形成和刺激 GRP 的产生 相同的远端上皮细胞。 具体目标是：1）表征 添加尼古丁对小鼠胚胎肺发育的影响 就特定基因表达而言，在无血清培养物中生长， 上皮细胞的生长、分支形态发生和分化 类型，2) 确定烟碱乙酰胆碱的性质和位置 受体介导尼古丁在肺中的发育作用 3）测试肽生长因子GRP及其受体在细胞中的作用 介导尼古丁对胚胎肺的影响。