The Genetics of Gene Targeting in Vertebrate Cells

描述（由申请人提供）： 本提案描述了一个为期5年的培训计划， 基于基础研究的儿科血液学/肿瘤学学术生涯 研究基因靶向的项目 主要研究者（PI） 完成了儿科住院医师（委员会认证）， 儿科血液学/肿瘤学（委员会认证），并正在完成霍华德 休斯医学研究所医师博士后奖学金。 的 指导临床科学家发展奖是唯一适合促进 PI的职业发展，因为他从博士后研究员 大学医学中心的初级教员 该计划有三个关键组成部分：赞助商，顾问 委员会和研究计划。 赞助商，大卫博士巴尔的摩有一个 在发展青年职业和启动基本 具有重要临床意义的研究项目。 咨询 由大卫、巴尔的摩、萨姆·勒克斯、斯图尔特·奥金和唐·科恩博士组成的委员会 由一批生物医学研究领域的学术领袖组成， 儿科血液学/肿瘤学和基因治疗。 他们是独一无二的 并致力于为PI的职业发展和研究提供建议 程序. 最后，本研究计划聚焦于基因这一重要领域 靶向脊椎动物细胞。 其总体目标是了解遗传学 使用绿色荧光蛋白（GFP）基因靶向的基因靶向（GT） PI开发的系统。 研究计划的具体目标 包括了解：1）GT的细胞周期调控; 2）GT的速率 在DT 40细胞中; 3）Rad 52在抑制GT中的作用; 4）GT在DT 40细胞中的比率。 与DNA双链断裂修复有关的突变细胞。 是 希望这些研究将导致基因治疗领域的进步， 在治疗儿童单基因疾病，如镰状细胞， 疾病

DESCRIPTION (provided by applicant): This proposal describes a 5-year training program for the development of an academic career in pediatric hematology/oncology based on a basic research program studying gene targeting. The principal investigator (PI) has completed a residency in pediatrics (board certified), a fellowship in pediatric hematology/oncology (board certified), and is completing a Howard Hughes Medical Institute Post-Doctoral Fellowship for Physicians. The Mentored Clinical Scientist Development Award is uniquely suited to promote the career development of the PI as he transitions from post-doctoral fellow to junior faculty at a university medical center. The program has three critical components: the sponsor, the advisory committee, and the research program. The sponsor, Dr. David Baltimore has an exceptional record in developing young careers and in initiating basic research programs with important clinical implications. The advisory committee of Drs. David Baltimore, Sam Lux, Stuart Orkin, and Don Kohn consists of a set of academic leaders in the fields of biomedical research, pediatric hematology/oncology and gene therapy. They are uniquely qualified and committed to advise the PI in both his career development and research program. Finally, the research program is focused on the important field of gene targeting in vertebrate cells. Its overall aim is to understand the genetics of gene targeting (GT) using a green fluorescent protein (GFP) gene targeting system that the PI developed. The specific aims of the research proposal include understanding: 1) the cell cycle regulation of GT; 2) the rate of GT in DT40 cells; 3) the role of Rad52 in inhibiting GT and; 4) the rate of GT in cells with mutations involved in DNA double-stranded break repair. It is hoped that such studies will lead to advances in the field of gene therapy and in the treatment of children with monogenic diseases, such as sickle cell disease.