MOLECULAR BIOLOGY OF UTERINE FUNCTION DURING PREGNANCY

怀孕期间子宫功能的分子生物学

• 批准号: 2731334
• 负责人: EDWARD K CHIEN
• 金额: $ 12.61万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2731334
• 关键词: binding sites; birth; female; fusion gene; gel mobility shift assay; gene expression; genetic mapping; genetic promoter element; genetic regulation; genetically modified animals; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; luciferin monooxygenase; messenger RNA; muscle function; myometrium; northern blottings; polymerase chain reaction; pregnancy; regulatory gene; transcription factor; western blottings

Edward K.S. Chien, M.D., received a baccalaureate degree in chemical engineering in 1984 and a medical degree in 1988 from the University of Illinois. Following his residency in Obstetrics and Gynecology at the University of Michigan Medical Center he completed a clinical fellowship in Maternal Fetal Medicine under the direction of Mark Phillippe, M.D., at the University of Chicago. During his clinical fellowship he worked in the laboratory of Dr. Mark Phillippe and investigated signal transduction mechanisms of myometrial cells. Two years ago Dr. Chien applied and received a Reproductive Scientist Development Program award. During that period of time he identified gestational regulated genes in the myometrium using differential messenger RNA display under the guidance of Dr. Graeme I. Bell, PhD. From these preliminary studies Dr. Chien has developed an extensive list of candidate genes which appear to be gestationally-regulated. The sponsor in the present application, Dr. Graeme Bell, is an international authority on monogenic and polygenic forms of diabetes mellitus and identified a number of transcription factors associated with maturity onset diabetes of the young. He has worked closely with Dr. Chien on all aspects of the present project. The broad, long-term objectives of this proposal is to identify and confirm, myometrial specific, gestationally-regulated genes and to understand the mechanisms surrounding their regulation. More specifically, the myometrium undergoes marked changes during pregnancy with significant changes in gene expression. The molecular mechanism behind these changes are to be identified. The regulatory elements of myometrial specific genes undergoing differential expression during pregnancy will be identified. These elements will be evaluated to determine their role in the changes related to pregnancy. Understanding the mechanism regulating changes in myometrial function will permit the development of novel therapies to treat preterm labor and post term pregnancies. The methods used to identify gestationally-regulated genes include differential mRNA display, cDNA array hybridization, and proteome analysis. Genomic sequences will be obtained by bacteriophage library screening after confirming tissue specific regulation with Northern blots and semi-quantitative reverse transcription-polymerase chain reaction. Regulatory regions are identified by cell transfection experiments with reporter gene constructs.

Edward K.S. Chien，医学博士，获得化学学士学位 1984年获得工程学学位，1988年获得哥伦比亚大学医学学位。 伊利诺 继他在妇产科住院医师在 密歇根大学医学中心，他完成了临床奖学金 在Mark Phillippe医学博士的指导下， 在芝加哥大学。 在临床研究期间， 在Mark Phillippe博士的实验室里， 子宫肌层细胞的转导机制。 两年前，钱博士申请并获得了生殖科学家的职位。 发展计划奖。 在这段时间里，他发现 子宫肌层中的妊娠调节基因， 信使RNA展示在格雷姆博士的指导下。Bell博士 从这些初步的研究中，钱博士列出了一个广泛的清单， 似乎受妊娠调控的候选基因。 的 本申请的发起人Graeme Bell博士是一位国际 糖尿病的单基因和多基因形式的权威， 确定了一些与成熟相关的转录因子， 年轻人的糖尿病。 他与钱博士密切合作， 本项目的所有方面。 这项建议的广泛和长期目标是确定和 确认，子宫肌层特异性，妊娠调节基因， 了解其调节机制。更 特别是子宫肌层在怀孕期间发生显著变化 基因表达发生了显著变化。 的分子机制 这些变化背后的原因有待查明。的调控元件 子宫肌层特异性基因在子宫发育过程中的差异表达 怀孕将被确认。这些元素将被评估， 确定它们在与怀孕有关的变化中的作用。 理解 调节子宫肌层功能变化的机制将允许 开发治疗早产和过期妊娠的新疗法 怀孕。 用于鉴定妊娠调控基因的方法包括 差异mRNA显示、cDNA阵列杂交和蛋白质组 分析. 基因组序列将通过噬菌体文库获得 在用北方RNA确认组织特异性调节后进行筛选 印迹和半定量逆转录聚合酶链 反应 通过细胞转染鉴定调控区 用报告基因构建体进行实验。