VERTEBRATE NON-LTR RETROTRANSPOSON

脊椎动物非 LTR 反转录转座子

• 批准号: 2517591
• 负责人: Naomi B Haas
• 金额: $ 8.23万
• 依托单位: RESEARCH INST OF FOX CHASE CAN CTR
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-15 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517591
• 关键词: genetic promoter element; genetic transcription; laboratory rabbit; molecular cloning; nucleic acid sequence; open reading frames; sperm; transposon /insertion element

A revised proposal is submitted to provide an apprenticeship in molecular biology for the candidate, who is a board-eligible Clinical Oncologist. The candidate was initially exposed to basic research during her clinical oncology training at Fox Chase Cancer Center and for the past year and a half has been engaged in full-time laboratory instruction in the field of transcriptional regulation. Her performance in clinical hematology and oncology, as well as her continued commitment to basic research, are documented in the proposal. The sponsor, John B. E. Burch, Ph.D., is a tenured member of Fox Chase Cancer Center and is a Member of the Graduate Group in Medical Biology and an Adjunct Associate Professor of Human Genetics at the University of Pennsylvania. He has trained both M.D. and Ph.D. Postdoctoral Fellows and his research program is supported through 1997 by an NIH RO1 grant, that was initially awarded in 1984. The sponsor has made significant contributions in two-fields of relevance to neoplasia; namely, retrotransposable elements and transcriptional regulation. The setting is Fox Chase Cancer Center, a comprehensive Cancer Center internationally known for its clinical and basic research. The training plan includes both a didactic program of instruction and an independent research project. The didactic training will include a textbook review of molecular biology, a weekly Journal club, a weekly Postdoctoral Training Course and yearly participation at major conferences on transcriptional regulation and cancer research. New comprehensive technical training will be acquired by executing an integrated set of experiments that have been designed to reveal the complete structure of chicken CR1 non-LTR retrotransposons and to determine the parameters that govern the retrotransposition of these elements. CR1 elements constitute only the third example of a vertebrate non-LTR retrotransposon family with a pol- like (reverse transcriptase) open reading frame. Moreover, CR1 elements are unique among all non-LTR retrotransposons with respect to the sequences that are present at the 3' ends of the retrotransposed copies, which suggests that they may use a novel strategy to prime their reverse transcription. The unusually high frequency of 5' truncations for retrotransposed CR1 elements will be exploited to isolate all of the potentially functional CR1 non-LTR retrotransposons. The issue as to whether external or internal promoters are used to transcribe the potentially functional CR1 non-LTR retrotransposons and the issue as to whether these elements can retrotranspose will be tested. These studies should provide evidence either for CR1 elements being self-propagating or for newly integrated elements being derived from a small number of master CR1 elements. The fact that CR1-like elements also exist in species from two non-avian vertebrate classes underscores the enormous impact that the retrotransposition of these elements has had to the mutation and evolution of diverse genomes. The proposed training program will provide the candidate with a solid foundation in molecular biology that should enable her to pursue an independent academic career in experimental oncology.

提交了一份修订后的提案，以提供分子学徒制度 生物学候选人，他是一名符合董事会资格的临床肿瘤学家。 这位候选人最初是在临床期间接触到基础研究的 福克斯·蔡斯癌症中心的肿瘤学培训，在过去的一年里 一半从事全职实验室教学工作，从事 转录调控。她在血液学和血液学方面的表现 肿瘤学以及她对基础研究的持续承诺，是 在建议书中有记录。赞助商John B.E.Burch博士是一位 福克斯·蔡斯癌症中心终身会员，研究生 医学生物学小组和人类兼职副教授 宾夕法尼亚大学的遗传学。他训练过医学博士和 博士后研究员和他的研究项目通过 1997年由NIH RO1拨款，最初是在1984年授予的。赞助商 在与以下两个领域相关的领域做出了重大贡献 肿瘤；即逆转录转座子和转录 监管。 背景是福克斯·蔡斯癌症中心，一家综合性的癌症中心 以其临床和基础研究而闻名国际。培训 该计划既包括教学计划，也包括独立的 研究项目。授课培训将包括教科书复习 分子生物学，周刊俱乐部，每周博士后培训 参加关于转录的主要会议的课程和年度 监管和癌症研究。新的综合技术培训将 通过执行一套集成的实验获得，这些实验 旨在揭示鸡CR1非LTR的完整结构 并确定控制逆转录转座子的参数 这些元素的逆转位。CR1元素仅构成 脊椎动物非LTR反转录转座子家族的第三个例子 如(逆转录酶)开放阅读框架。此外，CR1元素 在所有非LTR反转录转座子中都是独一无二的 存在于反转录转座拷贝的3‘端的序列， 这表明他们可能会使用一种新的策略来准备他们的反向投资 抄写。5‘截断的异常高频率 逆转座的CR1元件将被利用来分离所有 潜在功能的CR1非LTR反转录转座子。关于…的问题 无论是使用外部还是内部启动子来转录 潜在功能的CR1非LTR逆转录转座子及其相关问题 这些片段是否可以逆转座子将会受到测试。这些研究 应提供CR1元素是自传播的或 对于从少量主控件派生的新集成元素 CR1元素。类似CR1的元素也存在于来自 两类非鸟类脊椎动物强调了 这些元素的逆转位已经导致了突变和进化 多种多样的基因组。拟议的培训计划将提供 具有扎实的分子生物学基础的应聘者 她希望在实验肿瘤学方面追求独立的学术生涯。