Functional genomics resources for the Drosophila - TR&D1

项目总结-tr&d1 在这个项目中，我们专注于开发用于果蝇细胞和/或 在活体内。在细胞中的研究为利用功能丧失(例如： CRIPSR基因敲除和CRISPR干扰)和功能增益(例如CRISPR激活)方法，以及 作为在体内应用技术之前测试技术的有效平台。我们的计划权衡 风险相对较低的果蝇联合筛查方法风险较高，但潜在风险较高 有效开发新的CRISPR/CAS库和应用程序，例如使用不同的CAS9表格和 替代的Protspacer相邻基序、CRISPR抑制(CRISPRi)和/或基于CRISPR的靶向 核糖核酸。一组对使用筛查和活体技术研究癌症感兴趣的合作者，罕见 疾病、细胞生物学和其他主题将有助于测试和改进技术，并用于 特别是，来自多个项目的数据的积累将有助于改进试剂设计、数据分析、 目标预测等。总而言之，该项目将建立CRISPR集合格式屏幕作为一个强大的平台 为了分析保守的基因功能，以及产生新的和改进的细胞和体内方法， 有助于有效和高效地利用果蝇来研究健康和疾病。

PROJECT SUMMARY – TR&D1 In this project, we focus on development of functional genomics technologies for use in Drosophila cells and/or in vivo. Studies in cells provide a platform for large-scale gene function discovery using loss-of-function (e.g. CRIPSR knockout and CRISPR interference) and gain-of-function (e.g. CRISPR activation) approaches, and serves as an efficient platform to test technologies prior to their applications in vivo. Our plans balance relatively low-risk refinement of Drosophila pooled screen approaches with higher-risk but potentially highly impactful development of new CRISPR/Cas libraries and applications, e.g. using variant Cas9 forms with alternative protospacer-adjacent motifs, CRISPR inhibition (CRISPRi), and/or CRISPR-based targeting of RNA. A set of collaborators with interest in using screens and in vivo technologies to study cancer, rare diseases, cell biology, and other topics will help test and improve the technologies, and for screens in particular, the accumulation of data from multiple projects will help improve reagent design, data analysis, off- target prediction, etc. Altogether, this project will establish CRISPR pooled-format screens as a robust platform for analysis of conserved gene function, as well as result in new and improved cell and in vivo approaches, contributing to effective and efficient use of Drosophila to study health and disease.