The Genetics of Gene Targeting in Vertebrate Cells

描述(由申请人提供)： 这份提案描述了一项为期5年的培训计划，以发展 以基础研究为基础的儿科血液学/肿瘤学学术生涯 研究基因打靶的项目。首席调查员(PI)有 完成儿科住院医师资格(委员会认证)，在 儿科血液学/肿瘤学(委员会认证)，正在完成霍华德考试 休斯医学院内科医生博士后奖学金。这个 导师临床科学家发展奖是唯一适合推广的 从博士后到博士后的职业发展 给大学医学中心的初级教员。 该计划有三个关键组成部分：发起人、顾问 委员会，以及研究计划。赞助商大卫·巴尔的摩博士有一个 在发展年轻职业和启动基础设施方面有出色的记录 具有重要临床意义的研究计划。忠告 大卫·巴尔的摩、萨姆·莱克斯、斯图尔特·奥尔金和唐·科恩博士委员会 由一批生物医学研究领域的学术领袖组成， 儿童血液学/肿瘤学和基因治疗。他们是唯一有资格的人 并致力于为私家侦探提供职业发展和研究方面的建议 程序。 最后，将研究重点放在重要的基因领域。 以脊椎动物细胞为靶点。它的总体目标是理解遗传学 使用绿色荧光蛋白(GFP)基因打靶的基因打靶 PI开发的系统。研究提案的具体目标 包括了解：1)GT的细胞周期调节；2)GT的比率 在DT40细胞中；3)Rad52在抑制GT中的作用；4)GT在 突变的细胞参与了DNA双链断裂修复。它是 希望这些研究将导致基因治疗领域的进展和 在治疗患有单基因疾病的儿童中，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.