Enhancing the C. elegans animal resource through genome editing
通过基因组编辑增强线虫动物资源
基本信息
- 批准号:10271616
- 负责人:
- 金额:$ 60.52万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:ATP phosphohydrolaseAddressAllelesAnimal ModelAnimalsAreaAttentionBehaviorBiologyBiomedical ResearchCRISPR/Cas technologyCaenorhabditisCaenorhabditis elegansCandidate Disease GeneCategoriesClustered Regularly Interspaced Short Palindromic RepeatsCodeCollectionCommunitiesDatabasesDepositionDevelopmentDiseaseDissectionEquilibriumEventFundingG-Protein-Coupled ReceptorsGenerationsGenesGeneticGenomeGoalsGoldGuide RNAHandHealthHumanHuman BiologyHuman GeneticsInformation DistributionInstitutesInvertebratesIon ChannelKnock-inKnock-outLaboratoriesLeadLightMethodsMicroinjectionsModelingMolecularMolecular BiologyMolecular GeneticsMonitorMutationNeuronsOligonucleotidesOrthologous GenePathway interactionsPeptide HydrolasesPhasePhenotypePhosphotransferasesPhysiologyProductionProteinsProteomicsQuality ControlReagentReproducibilityResearchResearch PersonnelResearch Project GrantsResearch SupportResourcesScientistSiteUnited States National Institutes of HealthVariantWormBaseanimal resourcebasecommunity centerdesigngene discoverygene functiongene interactiongenetic analysisgenome editinggenome resourcehuman diseaseinterestknockout geneloss of functionloss of function mutationmetabolomicsmutantprogramsscreeningtranscriptome sequencingtrendvariant of unknown significanceweb site
项目摘要
Project Summary/Abstract
The objective of this project is to extend the C. elegans genetic toolkit available to researchers by providing
publicly available gene knockout (KO) mutations in genes of high value to those interested in human biology
and disease. C. elegans is a proven model for discovery of gene function and for embedding genes into
functional pathways, many of which were discovered in this transparent animal and are conserved in humans.
Loss-of-function mutations are the gold-standard for genetic analysis and allow inferences of gene function and
interaction. A relatively recent trend is that large-scale screens (e.g., RNA-seq, proteomics, natural variation
studies) generate long candidate gene lists for researchers to sort through and functionally validate, requiring
loss of function mutants in many genes to be examined. Having a community-driven resource generate KOs in
such genes provides reproducibility and an economy of scale that benefits all. We have developed an efficient
and high throughput CRISPR-Cas9 based gene knockout (KO) project to provide a set of precisely edited gene
knockout strains to the communities of C. elegans researchers and human geneticists. We seek to continue
the production phase of this project, thereby transformatively increasing the efficiency and impact of C. elegans
molecular genetics. We employ a highly coordinated three-site production strategy to generate KOs. Each
gene edit is carefully confirmed, and validated strains are grossly phenotyped and deposited into the
Caenorhabditis Genetics Center (CGC) strain collection along with detailed strain information for distribution to
the community. Strains are advertised through both the CGC and WormBase websites. We have generated
over 1,000 KOs to date; these KOs have supported a variety of research projects – spanning from mechanistic
studies of human variants to metabolomics – funded by at least 14 NIH Institutes and Centers, demonstrating
the high impact of our resource. We propose to continue to use our established pipelines to target an additional
2500 C. elegans orthologs of human genes. We will prioritize known or suspected human disease genes,
druggable gene classes, as well as understudied genes that are conserved to humans but that have no
actionable information. This is a multi-PI project which includes the lead-PIs of the CGC and of WormBase and
a subcontractor who maintains multiple community-centered databases, including a CRISPR guide RNA
selection site.
项目总结/摘要
该项目的目标是扩展C。elegans遗传工具包提供给研究人员,
对人类生物学感兴趣的人具有高价值的基因中的公开可用的基因敲除(KO)突变
和疾病C.线虫是发现基因功能和将基因嵌入
功能途径,其中许多是在这种透明的动物中发现的,在人类中是保守的。
功能丧失突变是遗传分析的金标准,可以推断基因功能,
互动相对最近的趋势是大规模屏幕(例如,RNA-seq,蛋白质组学,自然变异
研究)生成长的候选基因列表,供研究人员进行排序和功能验证,需要
许多基因的功能缺失突变体有待研究。拥有社区驱动的资源,
这些基因提供了可重复性和规模经济,使所有人受益。我们开发了一种高效的
和基于CRISPR-Cas9的高通量基因敲除(KO)项目,以提供一组精确编辑的基因,
敲除菌株对C.线虫研究者和人类遗传学家。我们寻求继续
该项目的生产阶段,从而转型提高C. elegans
分子遗传学我们采用高度协调的三地生产策略来产生科斯。每个
基因编辑被仔细确认,并且验证的菌株被粗略地表型化并被存放到
小杆线虫遗传学中心(CGC)菌株采集沿着详细菌株信息,以分发至
社会各界通过CGC和WormBase网站公布菌株。我们已经生成
迄今为止,有超过1,000个科斯;这些科斯支持了各种研究项目--从机械
代谢组学的人类变异研究-由至少14个NIH研究所和中心资助,证明
我们资源的巨大影响。我们建议继续利用现有的管道,
2500摄氏度人类基因的直向同源物。我们将优先考虑已知或疑似的人类疾病基因,
可药物化的基因类别,以及未充分研究的基因,这些基因在人类中是保守的,但没有
可采取行动的信息。这是一个多PI项目,包括CGC和WormBase的主要PI,
一个维护多个以社区为中心的数据库的分包商,包括CRISPR指导RNA
选择网站
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Ann E. Rougvie其他文献
Protein-DNA cross-linking as a means to determine the distribution of proteins on DNA in vivo.
蛋白质-DNA 交联是确定体内蛋白质在 DNA 上分布的一种手段。
- DOI:
10.1016/s0091-679x(08)60580-4 - 发表时间:
1991 - 期刊:
- 影响因子:0
- 作者:
David S. Gilmour;Ann E. Rougvie;Lis Jt - 通讯作者:
Lis Jt
Control of developmental timing in animals
动物发育时间的控制
- DOI:
10.1038/35088566 - 发表时间:
2001-09-01 - 期刊:
- 影响因子:52.000
- 作者:
Ann E. Rougvie - 通讯作者:
Ann E. Rougvie
Ann E. Rougvie的其他文献
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{{ truncateString('Ann E. Rougvie', 18)}}的其他基金
Enhancing the C. elegans animal resource through genome editing
通过基因组编辑增强线虫动物资源
- 批准号:
10610879 - 财政年份:2017
- 资助金额:
$ 60.52万 - 项目类别:
Enhancing the C. elegans animal resource through genome editing
通过基因组编辑增强线虫动物资源
- 批准号:
10453663 - 财政年份:2017
- 资助金额:
$ 60.52万 - 项目类别:
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