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Functional genomics resources for the Drosophila - TR&D1

果蝇功能基因组学资源 - TR

基本信息

批准号：
10436792
负责人：
STEPHANIE E MOHR
金额：
$ 32.67万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10436792
关键词：
Address Alleles Automobile Driving Biological Biological Assay CRISPR interference CRISPR screen CRISPR-mediated transcriptional activation CRISPR/Cas technology Cell Line Cells Cellular biology Chimeric Proteins Clustered Regularly Interspaced Short Palindromic Repeats Collaborations Communities Congenital disorders of glycosylation Data Data Analyses Data Pooling Development Disease Disease model Drosophila genus Ensure Equilibrium Genes Genome engineering Goals Guide RNA Health Image Infrastructure Knock-in Knock-out Learning Libraries Lipids Maintenance Malignant Neoplasms Methods Modification Molecular Genetics Morphology Organelles Other Genetics Performance Protein Secretion RNA RNA Interference RNA interference screen RNA library Rare Diseases Reagent Research Resistance Resources Risk System Techniques Technology Testing Variant Viral Work base cancer cell design functional genomics gain of function gene function genetic analysis genome wide screen genome-wide high risk improved in vivo in vivo evaluation innovation interest knockout gene large scale data loss of function screening success technology research and development tissue/cell culture tool

项目摘要

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.

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。