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

职业：用于全基因组筛选的多功能转录激活子样效应子库

• 批准号: 1351354
• 负责人: Leonidas Bleris
• 金额: $ 40万
• 依托单位: University of Texas at Dallas
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1351354&HistoricalAwards=false
• 关键词: CAREER; Versatile; transcription; activator; like

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.

1351354Bleris，Leonidas 在全基因组筛选实验中扰乱单个基因的能力对于揭示细胞和疾病特性发挥了重要作用。 PI 建议开发、优化和实施新型转录激活因子样效应器 (TALE) 库及相关技术。 TALE 是一种蛋白质，可以被设计为靶向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充当基因表达的激活剂或阻遏剂。虽然 TALE 文库技术具有广泛的应用前景，但该提案的重点在于开发和定制用于诱导多能干 (iPS) 细胞重编程的 TALE 文库。从疾病建模到治疗遗传疾病，iPS 的应用前景是无穷无尽的。考虑到 TALE 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，将引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审期刊上的出版物、会议记录以及在国内和国际会议上的演讲来传播。 PI 将开发一个关于系统生物学的定制专题课程，并将探讨学生网络和协作学习在教育中的作用和特性。此外，该教育计划还包括与研究紧密结合的几个行动项目，包括（a）支持德克萨斯大学达拉斯分校国际基因工程机器（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建立联系政策机构，(c) 科林社区学院的年度研讨会日以及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，该职业奖由生物技术、生物化学和生物质颁发工程计划CBET 部门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。