Functional genomics resources for the Drosophila - TR&D1

项目概要- TR&D1 在这个项目中，我们专注于开发用于果蝇细胞和/或 in vivo.在细胞中的研究提供了一个平台，用于大规模的基因功能发现使用功能丧失（例如， CRIPSR敲除和CRISPR干扰）和功能获得（例如CRISPR激活）方法，以及 作为一个有效的平台，在体内应用之前测试技术。我们的计划平衡 相对低风险的果蝇合并筛选方法的改进，具有较高的风险，但潜在的高度 有效开发新的CRISPR/Cas文库和应用，例如使用变体Cas9形式， 替代的前间区序列邻近基序、CRISPR抑制（CRISPRi）和/或基于CRISPR的靶向 核糖核酸一组有兴趣使用屏幕和体内技术研究癌症的合作者，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，并为屏幕在 特别是，多个项目的数据积累将有助于改进试剂设计，数据分析，关闭， 总之，该项目将建立CRISPR池格式筛选作为一个强大的平台 用于分析保守基因功能，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.