CAREER: Versatile transcription activator-like effector libraries for genome-wide screens

在全基因组筛选实验中干扰单个基因的能力在揭示细胞和疾病特性方面发挥了重要作用。PI建议开发、优化和实现新的转录激活因子样效应器（TALE）库和相关技术。tale是一种蛋白质，可以被设计成针对哺乳动物细胞中的特定核苷酸序列，并且可以在转录水平上作为基因表达的激活剂或抑制剂。虽然TALE文库技术具有广泛的应用前景，但本提案的重点在于开发和定制用于诱导多能干细胞重编程的TALE文库。从疾病建模到基因疾病的治疗，iPS的应用前景是无限的。考虑到TALEs的高度模块化性质以及构建这些库的多功能性和易用性，该技术具有变革性，并将激发大量新颖的生物技术和医学应用。研究结果将通过同行评议期刊的出版物、会议记录以及在国家和国际会议上的演讲来传播。PI将开发一门关于系统生物学的定制专题课程，并将探讨学生网络和协作学习在教育中的作用和性质。此外，教育计划包括几个与研究紧密结合的行动项目，包括(a)支持德州大学达拉斯国际基因工程机器（IGEM）本科合成生物学团队，(b)通过与美国领先的研究和科学政策机构的实习机会进行对接，(c)在科林社区学院举行年度研讨会日和在我们实验室举办的暑期实习，以及(d)实验室社区服务。由于该项目的跨学科性质，CBET部门的生物技术、生化和生物质工程项目的CAREER奖由分子和细胞生物学部门的系统和合成生物学项目共同资助。

1351354Bleris, Leonidas The ability to perturb individual genes in genome-wide screening experiments has been instrumental in unraveling cellular and disease properties. The PI proposes to develop, optimize, and implement novel transcription-activator like effector (TALE) libraries and associated technologies. TALEs are proteins that can be engineered to target specific nucleotide sequences in mammalian cells and can act as activators or repressors of gene expression at the transcriptional level. While the TALE library technology holds promise for a wide range of applications, the emphasis of this proposal lies in the development and customization of TALE libraries for induced pluripotent stem (iPS) cell reprogramming. From disease modeling to curing genetic diseases, the prospective iPS applications are endless. Considering the highly modular nature of TALEs and the versatility and ease of constructing these libraries, the technology is transformative and will spark a large number of novel biotechnology and medical applications. The results will be disseminated through publications in peer-reviewed journals, conference proceedings, and presentations at national and international conferences. The PI will develop a customized special topics class on systems biology and the role and properties of student networks and collaborative learning in education will be explored. In addition, the educational plan consists of several action items tightly integrated with research, including (a) support for the UT Dallas International Genetically Engineered Machine (IGEM) undergraduate synthetic biology team, (b) interfacing via internship opportunities with leading US research and science policy institutions, (c) annual seminar day at Collin Community College and a summer internship hosted in our lab, and (d) lab community service.Due to the interdisciplinary nature of the project, this CAREER award by the Biotechnology, Biochemical, and Biomass Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology.