Delineation of CRISPR-Cas invader defense pathways in Streptococcus thermophilus

嗜热链球菌 CRISPR-Cas 入侵防御途径的描述

• 批准号: 8840970
• 负责人: MICHAEL P TERNS
• 金额: $ 28.22万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8840970
• 关键词: Address; Antibiotic Resistance; Bacteria; Biogenesis; Biological; Cell-Free System; Cleaved cell; Clustered Regularly Interspaced Short Palindromic Repeats; Complex; DNA; DNA Sequence; Data; Enzymes; Food; Genome; Goals; Guide RNA; Human; Immune response; Immune system; Infection; Invaded; Laboratories; Lead; Molecular; Nucleic Acids; Pathway interactions; Pharmacologic Substance; Phase; Plasmids; Process; Prokaryotic Cells; Proteins; RNA; RNA Sequences; Reaction; Scientist; Seminal; Site; Small RNA; Streptococcus thermophilus; System; Testing; Transcript; Variant; Viral; Virus; Work; base; combat; endoribonuclease; human BCAR1 protein; human disease; in vivo; insight; interest; pathogen; plasmid DNA; prospective; protein function; reconstitution; research study; response; transcriptome sequencing; viral DNA

DESCRIPTION (provided by applicant): CRISPR-Cas systems are recently discovered, RNA-based immune systems that control invasions of viruses and plasmids in prokaryotes. Prokaryotes with CRISPR-Cas systems capture short invader sequences within the CRISPR loci in their genomes, and small RNAs produced from the CRISPR loci (CRISPR (cr)RNAs) are thought to guide Cas proteins to recognize and silence the invading nucleic acids; however, we know very little about how the key steps in the remarkable CRISPR-Cas immune response pathways occur. In this project, we address the molecular basis for the three steps required for CRISPR-Cas defense through the following specific aims: ¿ Determine how CRISPR loci acquire foreign DNA sequences ¿ Determine the mechanisms by which functional CRISPR RNAs are produced ¿ Delineate the mechanisms of invader silencing Specifically, we aim to obtain a molecular understanding of the CRISPR-Cas defense pathways that function in Streptococcus thermophilus. We will identify the essential cellular machinery (proteins and RNAs) and molecular mechanisms involved in each of the three key phases of CRISPR-Cas defense. We hypothesize that Cas proteins function in each of the major steps in the defense pathway, and we will test this and a number of specific related hypotheses in the proposed studies. The experiments will define the CRISPR-Cas pathways used by multitudes of prokaryotes to survive viral attack. The information gained in this study will contribute directly o ongoing efforts aimed at exploiting CRISPR-Cas systems to both strengthen domesticated bacteria (used to produce safe food, pharmaceuticals and biofuels) and weaken human pathogens and limit the spread of antibiotic resistance.

描述（由申请人提供）：CRISPR-Cas系统是最近发现的基于RNA的免疫系统，其控制原核生物中的病毒和质粒的入侵，具有CRISPR-Cas系统的原核生物捕获其基因组中的CRISPR位点内的短入侵者序列和小入侵者序列。人们认为，由 CRISPR 位点 (CRISPR (cr)RNA) 产生的 RNA 可以引导 Cas 蛋白识别并沉默入侵的核酸，但我们对此知之甚少。关于非凡的 CRISPR-Cas 免疫反应途径中的关键步骤是如何发生的 在这个项目中，我们通过以下具体目标来解决 CRISPR-Cas 防御所需的三个步骤的分子基础： ¿确定 CRISPR 基因座如何获取外源 DNA 序列 ¿确定功能性 CRISPR RNA 的产生机制 ¿具体描述入侵者沉默的机制，我们的目标是获得对嗜热链球菌中发挥作用的 CRISPR-Cas 防御途径的分子理解，我们将确定涉及三个关键的基本细胞机制（蛋白质和 RNA）和分子机制。我们探究了 Cas 蛋白在防御途径的每个主要步骤中的功能，我们将在拟议的研究中测试这一点以及一些具体的相关假设。多种原核生物利用 CRISPR-Cas 途径抵御病毒攻击。本研究中获得的信息将直接有助于旨在利用 CRISPR-Cas 系统增强驯化细菌（用于生产安全食品、药品和生物燃料）和增强驯化细菌的努力。削弱人类病原体并限制抗生素耐药性的传播。

项目成果

Cas9 function and host genome sampling in Type II-A CRISPR-Cas adaptation.

• DOI: 10.1101/gad.257550.114
• 发表时间: 2015-02-15
• 期刊: Genes & development
• 影响因子: 10.5
• 作者: Wei Y;Terns RM;Terns MP
• 通讯作者: Terns MP

Immunological profiles associated with distinct parasitemic states in volunteers undergoing malaria challenge in Gabon.

• DOI: 10.1038/s41598-022-17725-8
• 发表时间: 2022-08-03
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Manurung, Mikhael D.;de Jong, Sanne E.;Kruize, Yvonne;Mouwenda, Yoanne D.;Ongwe, Madeleine Eunice Betouke;Honkpehedji, Yabo Josiane;Zinsou, Jeannot Frezus;Dejon-Agobe, Jean Claude;Hoffman, Stephen L.;Kremsner, Peter G.;Adegnika, Ayola Akim;Fendel, Rolf;Mordmuller, Benjamin;Roestenberg, Meta;Lell, Bertrand;Yazdanbakhsh, Maria
• 通讯作者: Yazdanbakhsh, Maria

Sequences spanning the leader-repeat junction mediate CRISPR adaptation to phage in Streptococcus thermophilus.

• DOI: 10.1093/nar/gku1407
• 发表时间: 2015-02-18
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Wei Y;Chesne MT;Terns RM;Terns MP
• 通讯作者: Terns MP