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解开细胞和疾病特性方面起到了重要作用。PI建议开发、优化和实现新的转录激活物样效应器(TALL)文库和相关技术。TALE是一种蛋白质，可以被改造成针对哺乳动物细胞中的特定核苷酸序列，并可以在转录水平上作为基因表达的激活或抑制因子。尽管TALL文库技术具有广泛的应用前景，但这一提议的重点在于开发和定制用于诱导多能干细胞(IPS)重新编程的TALL文库。从疾病模型到治疗遗传病，iPS的应用前景无限。考虑到故事的高度模块化性质以及构建这些图书馆的多功能性和简便性，这项技术具有变革性，将引发大量新的生物技术和医疗应用。这些成果将通过同行评议期刊上的出版物、会议记录以及在国内和国际会议上的发言来传播。PI将开发一个关于系统生物学的定制专题课程，并将探索学生网络和协作学习在教育中的作用和特性。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)支持德克萨斯大学达拉斯国际基因工程机械(IGEM)本科合成生物学团队，(B)通过实习机会与美国领先的研究和科学政策机构建立联系，(C)科林社区学院的年度研讨会日和我们实验室主办的暑期实习，以及(D)实验室社区服务。

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.