Mechanistic Investigation of RNA-Mediated Gene Regulation and Immunity

RNA介导的基因调控和免疫的机制研究

基本信息

批准号：
10445317
负责人：
Ailong Ke
金额：
$ 66.83万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10445317
关键词：
Adopted Antibiotics Area Bacteria Bacterial Physiology Biochemical Biological Process Biology Biophysics Biotechnology Clustered Regularly Interspaced Short Palindromic Repeats Development Essential Genes Eukaryota Gene Expression Regulation Genetic Screening Immunity Integrase Investigation Ligands Mediating Medicine Molecular Conformation Molecular Genetics Operon Orphan Proteins RNA RNA Interference Research Resolution Structure System Virulence Work base genome editing genomic tools human pathogen insight novel pathogenic microbe programs

Adopted Antibiotics Area Bacteria Bacterial Physiology Biochemical Biological Process Biology Biophysics Biotechnology Clustered Regularly Interspaced Short Palindromic Repeats Development Essential Genes Eukaryota Gene Expression Regulation Genetic Screening Immunity Integrase Investigation Ligands Mediating Medicine Molecular Conformation Molecular Genetics Operon Orphan Proteins RNA RNA Interference Research Resolution Structure System Virulence Work base genome editing genomic tools human pathogen insight novel pathogenic microbe programs

展开

项目摘要

Project Summary The proposed research combines biophysics, molecular genetics, and genomics tools to provide high-resolution mechanisms for RNA-dominated biological processes. Our study focuses on two central themes in RNA biology. (1) RNA can serve as an information carrier to guide the action of proteins. Such systems are inherently precise and programmable, therefore carry great potential in biotechnology and medicine, as exemplified by RNAi and CRISPR-Cas. My lab spent more than ten years dissecting the mechanisms of CRISPR-Cas, and more recently has been developing genome editing applications based on our mechanistic insights. (2) RNA can adopt defined tertiary structures to exert important functions. My lab has elucidated the structure, function, and conformation dynamics of many riboswitches. The high-resolution information may enable new antibiotics development. We now aim to combine genetic screen with biochemical purification to systematically identify ligands for orphan riboswitches. Such studies often reveal novel aspects of bacterial physiology, which may even be conserved in eukaryotes. We propose to work on the following four areas of research: 1) Structure, mechanism, and genome editing applications of Type I CRISPR (CRISPR-Cas3); 2) Mechanism of CRISPR immunity establishment by Cas1-Cas2 integrase; 3) Mechanism and genome editing application of CRISPR-Tn7; 4) Dissecting riboswitch- controlled mechanism and bacterial physiology.

项目摘要拟议的研究结合了生物物理学，分子遗传学和基因组学工具，以提供高分辨率 RNA主导的生物过程的机制。我们的研究重点是RNA生物学中的两个中心主题。（1）RNA可以用作指导蛋白质作用的信息载体。这样的系统本质上是精确的因此，RNAi和 CRISPR-CAS。我的实验室花了十多年的时间来剖析CRISPR-CAS的机制，最近一直在基于我们的机械见解开发基因组编辑应用。（2）RNA可以采用定义的三级结构发挥重要功能。我的实验室阐明了结构，功能和构象许多核糖开关的动力学。高分辨率信息可能会引发新的抗生素开发。我们现在，旨在将遗传筛选与生化纯化结合起来，以系统地识别孤儿的配体核糖开关。这样的研究经常揭示细菌生理学的新方面，甚至可以在真核生物。我们建议研究以下四个研究领域：1）结构，机制和基因组 I型CRISPR（CRISPR-CAS3）的编辑应用； 2）CRISPR免疫机制建立 Cas1-Cas2集成酶； 3）CRISPR-TN7的机制和基因组编辑应用； 4）解剖核糖开关 - 受控机制和细菌生理学。