VERTEBRATE NON-LTR RETROTRANSPOSON

提交了一份修订后的提案， 生物学的候选人，谁是一个董事会合格的临床肿瘤学家。 该候选人最初在临床期间接触基础研究 在福克斯大通癌症中心的肿瘤学培训，并在过去的一年里， 其中一半从事全日制实验室教学， 转录调控她在临床血液学方面的表现， 肿瘤学，以及她对基础研究的持续承诺， 记录在提案中。赞助商约翰B。E.伯奇博士，是一 福克斯大通癌症中心的终身会员，是研究生院的成员 医学生物学小组和人类学兼职副教授 宾夕法尼亚大学的遗传学。他训练了两个医生。和 博士博士后研究员和他的研究计划是通过支持 1997年由NIH RO 1资助，最初于1984年授予。申办者 在两个相关领域做出了重大贡献， 肿瘤;即，逆转录转座因子和转录因子 调控 福克斯蔡斯癌症中心（Fox Chase Cancer Center）是一家综合性癌症中心。 以其临床和基础研究而享誉国际。培训 计划包括教学的教学计划和一个独立的 研究项目。教学培训将包括对以下内容的教科书审查： 分子生物学，每周期刊俱乐部，每周博士后培训 课程和每年参加关于转录的主要会议 监管和癌症研究。新的全面技术培训将 通过执行一组完整的实验来获得， 旨在揭示鸡CR 1非LTR的完整结构 反转录转座子，并确定控制 这些元素的反转录。CR 1元件仅构成 第三个例子是脊椎动物非LTR反转录转座子家族， 像（逆转录酶）开放阅读框架。此外，CR 1元件 在所有非LTR反转录转座子中， 存在于逆转录转座拷贝的3 ′末端的序列， 这表明它们可能会使用一种新的策略来启动它们的逆转 转录。5'截短的异常高频率 将利用反转录的CR 1元件来分离所有的 CR 1非LTR反转录转座子。之问题 无论是外部启动子还是内部启动子用于转录 潜在的功能性CR 1非LTR反转录转座子和关于 这些元素是否可以逆转将被测试。这些研究 应该提供证据，要么CR 1元素是自传播的， 对于新集成的元素是从少量的主元素导出的 CR 1元素。事实上，CR 1样元素也存在于物种中， 两个非鸟类脊椎动物类强调了巨大的影响， 这些元件的逆转录转座导致了突变和进化 多样的基因组。拟议的培训方案将提供 候选人在分子生物学方面有坚实的基础，应该能够 她在实验肿瘤学方面追求独立的学术生涯。

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.