VERTEBRATE NON-LTR RETROTRANSPOSON

脊椎动物非 LTR 反转录转座子

• 批准号: 2104764
• 负责人: Naomi B Haas
• 金额: $ 8.1万
• 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/2104764
• 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，以提供分子学徒培训 候选人是符合委员会资格的临床肿瘤学家。 候选人在临床期间最初接触了基础研究 福克斯蔡斯癌症中心的肿瘤学培训以及过去的一年和 一半从事该领域的全职实验室教学 转录调控。她在临床血液学和 肿瘤学以及她对基础研究的持续承诺 记录在提案中。发起人 John B. E. Burch 博士是 福克斯蔡斯癌症中心终身会员，也是研究生会员 医学生物学组和人类学兼职副教授 宾夕法尼亚大学遗传学。他曾培训过医学博士和 博士博士后研究员及其研究计划通过以下方式获得支持 1997 年获得 NIH RO1 资助，该资助最初于 1984 年授予。 在两个相关领域做出了重大贡献 肿瘤；即逆转录转座元件和转录元件 规定。 地点是福克斯蔡斯癌症中心 (Fox Chase Cancer Center)，这是一家综合性癌症中心 因其临床和基础研究而享誉国际。培训内容 计划包括教学计划和独立的 研究项目。教学培训将包括教科书审查 分子生物学、每周期刊俱乐部、每周博士后培训 转录相关主要会议的课程和年度参与 监管和癌症研究。新的综合技术培训将 通过执行一组集成的实验来获得 旨在揭示鸡 CR1 非 LTR 的完整结构 逆转录转座子并确定控制逆转录转座子的参数 这些元件的逆转录转座。 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 像（逆转录酶）开放阅读框。此外，CR1元素 在所有非 LTR 反转录转座子中是独一无二的 存在于逆转录转座拷贝 3' 端的序列， 这表明他们可能会使用一种新颖的策略来启动他们的逆转 转录。 5' 截断的频率异常高 逆转录转座 CR1 元件将被用来分离所有 具有潜在功能的 CR1 非 LTR 反转录转座子。问题是关于 无论使用外部还是内部启动子来转录 潜在功能性 CR1 非 LTR 反转录转座子以及有关的问题 这些元件是否可以逆转座将被测试。这些研究 应提供 CR1 元素自我传播的证据或 对于来自少数大师的新整合元素 CR1 元素。事实上，CR1 样元素也存在于以下物种中： 两个非鸟类脊椎动物纲强调了 这些元件的逆转录转座导致了突变和进化 不同的基因组。拟议的培训计划将提供 具有扎实的分子生物学基础的候选人，应该能够 她在实验肿瘤学领域追求独立的学术生涯。