RNA Mediated Genetic Interference in C. elegans

RNA 介导的线虫遗传干扰

• 批准号: 7262042
• 负责人: CRAIG C MELLO
• 金额: $ 33.31万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7262042
• 关键词: Address; Alleles; Animals; Binding Proteins; Biochemical Genetics; Biological Models; Caenorhabditis elegans; Cell Nucleus; Chromatin; Chromosome Segregation; Coin; Collaborations; Cytoplasm; Defect; Development; Disease; Embryo; Embryonic Development; Essential Genes; Event; Exhibits; Fertility; Fire - disasters; Funding; Future; Gene Expression; Gene Expression Regulation; Gene Silencing; Generations; Genes; Genetic; Genetic Materials; Genetic Screening; Genome; Genomics; Goals; Human; Human Development; Investigation; Kinetochores; Knock-out; Laboratories; Lead; Maintenance; Maps; Mediating; Medical Research; Messenger RNA; Methodology; Methods; Molecular; Mutation; Nematoda; Organism; Outcome; Paper; Pathway interactions; Phenotype; Placement; Plants; Proteins; Proteomics; RNA; RNA Interference; RNA Interference Pathway; Regulator Genes; Research; Research Personnel; Screening procedure; Site-Directed Mutagenesis; Technology; Temperature; Tetrahymena; Time; Translations; Work; clinical application; cofactor; improved; insight; mutant; novel; positional cloning; programs; response; tool

DESCRIPTION (provided by applicant): RNA interference (RNAi) has become an important new tool for the targeted inhibition of gene expression. RNAi methodologies are accelerating basic medical research in numerous fields and have many potential clinical applications. However, there are still many gaps in our understanding of the basic mechanism of RNAi. The research proposed here is directed at understanding RNAi and improving related technologies for gene silencing. We now posses a basic outline of the core mechanism of RNAi, and an understanding of how related mechanisms are important in genome maintenance and developmental gene regulation in a variety of animals and plants. The proposed studies will address the following questions: (i) How are RNAi silencing mechanisms triggered? (ii) How do the RNAi and developmental pathways, which employ similar mechanisms, mediate distinct outcomes, mRNA destruction, translation inhibition and transcriptional silencing? and (iii) what additional gene products function in RNAi and related pathways? These questions will be addressed with an integrated set of molecular, biochemical and genetic methods using the nematode Caenorhabditis elegans as a model system. The findings from these studies will advance our understanding of RNAi and of related pathways in other organisms including humans and may lead to improved genetic interference technologies. Moreover, the genetic mechanisms of RNAi are related to ancient gene-regulatory mechanisms and are thus likely to be relevant to many aspects of human development and disease.

描述（由申请人提供）：RNA干扰（RNAi）已成为靶向抑制基因表达的重要新工具。RNAi方法正在加速许多领域的基础医学研究，并具有许多潜在的临床应用。然而，我们对RNAi的基本机制的理解仍然存在许多空白。本文的研究目的是为了更好地理解RNAi并改进基因沉默的相关技术。我们现在对RNAi的核心机制进行了基本概述，并了解了相关机制在各种动物和植物的基因组维持和发育基因调控中的重要性。拟议的研究将解决以下问题：（i）RNAi沉默机制是如何触发的？(ii)采用类似机制的RNA干扰和发育途径如何介导不同的结果、mRNA破坏、翻译抑制和转录沉默？以及（iii）在RNAi和相关途径中有哪些额外的基因产物起作用？这些问题将解决一套完整的分子，生物化学和遗传学的方法，线虫作为一个模型系统。这些研究的发现将促进我们对RNAi以及包括人类在内的其他生物体中相关途径的理解，并可能导致改进遗传干扰技术。此外，RNAi的遗传机制与古老的基因调控机制有关，因此可能与人类发育和疾病的许多方面有关。