XRCC4 AND V<D>J RECOMBINATION AND DNA REPAIR

说明： 候选人：凯伦·M·弗兰克博士获得医学博士学位和博士学位 1994年在宾夕法尼亚大学就读。她一直是个临床病理学家 布里格姆妇女医院和儿童医院住院医生兼研究员 自1994年起在医院就诊。曾任临床病理学总住院医师。 布里格姆妇产科医院1996年1月至1996年6月。弗兰克博士 列出了六篇已发表的论文，其中她是其中四篇的第一作者。这个 候选人的目标是在一个主要的医学中心进行免疫学研究 与学术教授的任命，以及与联合任命在一个 三级护理医院。 导师：弗雷德里克·阿尔特博士是查尔斯·简威的儿科学教授 和哈佛医学院遗传学和儿科学教授，以及 霍华德·休斯儿童医学研究所的研究员 医院。 C.职业发展计划：应聘者将85%-90%的时间用于 研究。她将学习分子生物学的新技术，增加她的 免疫学知识，培养实验设计和实验技能 介绍研究成果。我们将花费一定的时间 到教学，到学习管理实验室。 D.研究计划：Frank博士建议研究脑细胞的功能 新克隆的V(D)J重组基因XRCC4。XRCC4是 在导师的实验室里隔离基于它的潜力 V(D)J重组与双链DNA断裂 修理。 该项目的假设是XRCC4蛋白起着直接作用 在V(D)J复合过程中。将使用三种方法来 解决这个假设。在具体目标1中，弗兰克博士将尝试 通过突变分析确定XRCC4的功能结构域 研究氨基酸序列的进化保守性。弗兰克博士 还将尝试确定XRCC4是否被磷酸化以及是否 磷酸化对其功能有任何作用。在《特定目标2》中，弗兰克博士 建议调查XRCC4是否与已知的V(D)J有关 重组组分如RAG-1、RAG-2、Ku 80、Ku 70和DNA-PKCS以及 其他新发现的蛋白质。在《特定目标3》中，弗兰克博士将产生 XRCC4基因敲除(KO)小鼠及XRCC4在淋巴细胞中的作用 在发育和DNA修复方面。 E.环境和机构支助：培训将在#年进行 阿尔特博士在儿童医院恩德斯研究大楼的实验室 医院。

DESCRIPTION: a. Candidate: Dr. Karen M. Frank received her M.D. and Ph.D. degrees from the University of Pennsylvania in 1994. She has been a clinical pathology resident and research fellow at Brigham and Women's Hospital and Children's Hospital since 1994. She served as Chief Resident in clinical pathology at Brigham and Women's Hospital from January 1996 to June 1996. Dr. Frank listed six published papers, in which she was first author on four. The candidate's goal is to perform immunology research at a major medical center with an academic faculty appointment, and with a joint appointment in a tertiary care hospital. b. Mentor: Dr. Frederick Alt is the Charles Janeway Professor of Pediatrics and Professor of Genetics and Pediatrics at the Harvard Medical School, and an Investigator of the Howard Hughes Medical Institute at the Children's Hospital. c. Career Development Plan: The candidate will devote 85-90 percent time to research. She will learn new techniques in molecular biology, increase her knowledge of immunology, and develop skills in experimental design and presentation of research results. A modest amount of time will be devoted to teaching and to learning to manage a laboratory. d. Research Plan: Dr. Frank proposes to investigate the function of the newly cloned gene XRCC4 in the V(D)J recombination process. XRCC4 was isolated in the mentor's laboratory on the basis of its potential involvement in V(D)J recombination and double stranded (DS) DNA break repair. The hypothesis of the project is that the XRCC4 protein plays a direct role in the V(D)J recombination process. Three approaches will be used to address the hypothesis. In Specific Aim 1, Dr. Frank will attempt to determine functional domains of XRCC4 by mutational analysis and by examining the evolutionary conservation of amino acid sequence. Dr. Frank will also try to determine if XRCC4 is phosphorylated and whether phosphorylation has any role in its function. In Specific Aim 2, Dr. Frank proposes to investigate whether XRCC4 associates with known V(D)J recombination components such as RAG-1, RAG-2, Ku 80, Ku 70 and DNA-PKCS and other newly discovered proteins. In Specific Aim 3, Dr. Frank will generate XRCC4 knockout (KO) mice and study the role of XRCC4 in lymphocyte development and in DNA repair. e. Environment and Institutional Support: The training will take place in Dr. Alt's laboratory in the Enders Research Building of the Children's Hospital.