RNA Mediated Genetic Interference in C. elegans

RNA 介导的线虫遗传干扰

基本信息

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
项目类别：
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

项目摘要

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（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的基本机制的理解还存在很多差距。这里提出的研究旨在了解 RNAi 并改进基因沉默的相关技术。我们现在对 RNAi 的核心机制有了基本的了解，并了解了相关机制在各种动植物基因组维护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) RNAi 和发育途径采用相似的机制，如何介导不同的结果、mRNA 破坏、翻译抑制和转录沉默？ (iii) 还有哪些基因产物在 RNAi 和相关途径中发挥作用？这些问题将通过使用线虫秀丽隐杆线虫作为模型系统的一套综合的分子、生化和遗传学方法来解决。这些研究的结果将增进我们对 RNAi 以及包括人类在内的其他生物体相关途径的理解，并可能导致遗传干扰技术的改进。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。