REGULATION OF THE RAT VIP RECEPTOR GENE

大鼠 VIP 受体基因的调控

• 批准号: 2518162
• 负责人: LIN PEI
• 金额: $ 8.81万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518162
• 关键词: DNA binding protein; RNase protection assay; animal genetic material tag; biological signal transduction; developmental genetics; embryo /fetus; embryonic stem cell; gene targeting; genetic regulation; genetically modified animals; histogenesis; hormone receptor; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; lung; lung neoplasms; mammalian embryology; neuropeptide receptor; point mutation; receptor expression; site directed mutagenesis; transcription factor; vasoactive intestinal peptide

Research: The broad spectrum of VIP biological functions are mediated by its receptor. In the lung, VIP acts as a potent smooth muscle relaxant and it may also regulate lung cancer proliferation. The long-term goal of this proposal is to determine molecular mechanisms that regulate VIP receptor expression during development and in disease. The specific aims are to isolate and characterized the rat VIP receptor gene (2). Identity regulatory elements and factors that control VIP receptor transcription in both normal and cancerous lung cells transfection and DNA-protein binding assays (3). Study the regulation of VIP receptor expression during development by in situ hybridization and by homologous recombination to generate mice that lack functional VIP receptors. These studies will provide important insight into the physiology of VIP receptor regulation and function to this ubiquitous hormone. This will lead to enhanced understanding mechanisms for VIP-responsive malignancies. Candidate: Dr. Lin Pei, M.D., Ph.D., has a strong background training in molecular biology. During early postdoctoral training at UCLA, she also acquired skills in protein chemistry. This will enable her to effectively perform and interpret the experiments in this proposal. Dr. Pei is committed to applying molecular biological techniques to answer questions of disease pathophysiology and is embarked on a career in academic medicine. She is assured of Departmental support as an independent faculty member both during and by the end of the award. Environment: The applicant will perform the research in the well-equipped laboratory of the sponsor which is funded as a NIDDK Program Project in endocrine aspects of neoplasia. As such, Dr. Pei's proposal will meet with the overall goals of the group. She will have full access to all core facilities available in the Davis Research Building including molecular oligonucleotide synthesis, transgenic mouse and vivarium. There are weekly research-in-progress laboratory meeting, departmental research seminars and visiting scientists (growth factors, transcription, gene regulator) providing continued exposure to basic and clinical research advances. In addition, Dr. Pei will enjoy the continued exposure to the expert endocrine faculty at Cedars-Sinai, as well as associated productive groups in molecular genetics, membrane biology, transplantation biology, virology and protein chemistry.

研究：VIP的广谱生物学功能是由 它的受体。在肺中，VIP充当有效的平滑肌松弛剂， 它还可以调节肺癌增殖。长期目标是 一项旨在确定调节VIP受体的分子机制的提案 在发育和疾病中表达。具体目标是 分离并鉴定大鼠VIP受体基因（2）。身份 VIP受体转录的调控元件和因子 正常和癌性肺细胞转染和DNA-蛋白质结合 分析（3）。研究血管活性肠肽受体表达的调控 通过原位杂交和同源重组， 产生缺乏功能性VIP受体的小鼠。这些研究将 为VIP受体调节的生理学提供了重要的见解 并对这种无处不在的激素起作用。这将导致增强 了解VIP反应性恶性肿瘤的机制。 候选人：林培博士，医学博士，哲学博士、有很强的背景训练， 分子生物学在加州大学洛杉矶分校的早期博士后培训期间，她还 获得蛋白质化学方面的技能。这将使她能够有效地 执行并解释本提案中的实验。裴博士是 致力于应用分子生物学技术来回答 疾病病理生理学，并开始了学术生涯， 药她作为一个独立的教师， 在颁奖期间和颁奖结束时。 环境：申请人将在设备齐全的 作为NIDDK计划项目资助的赞助商实验室， 肿瘤的内分泌方面。因此，裴博士的建议将符合 集团的总体目标。她将可以完全访问 戴维斯研究大楼的设施，包括分子 寡核苷酸合成，转基因小鼠和动物饲养场。每周有 进行中的研究实验室会议，部门研究研讨会 和访问科学家（生长因子，转录，基因调节） 持续接触基础和临床研究进展。在 此外，裴博士将继续享受与专家的接触， Cedars-Sinai的内分泌系以及相关的生产小组 分子遗传学、膜生物学、移植生物学、病毒学 和蛋白质化学