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.

项目摘要 - TR＆D1 在这个项目中，我们着重于开发用于果蝇细胞和/或的功能基因组技术技术体内。细胞中的研究为使用功能丧失的大规模基因功能发现提供了一个平台（例如 CRIPSR敲除和CRISPR干扰）和功能获得（例如CRISPR激活）方法，以及在其在体内应用之前，它是测试技术的有效平台。我们的计划平衡果蝇合并屏幕方法相关的低风险优化，具有更高风险但可能高度的高风险有影响力的新CRISPR/CAS库和应用程序，例如使用变体cas9表格与替代的原始探针添加主题，CRISPR抑制（CRISPRI）和/或基于CRISPR的靶向 RNA。一系列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，并在特别是，来自多个项目的数据积累将有助于改善试剂设计，数据分析，外目标预测等。总的来说，该项目将建立CRISPR合并格式屏幕作为强大的平台为了分析配置的基因功能，并导致新的和改进的细胞和体内方法，有助于有效地利用果蝇研究健康和疾病。