Structural and functional understanding of bacterial defense and viral counter defense

对细菌防御和病毒反防御的结构和功能的理解

• 批准号: 10552596
• 负责人: Blake A Wiedenheft
• 金额: $ 53.74万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10552596
• 关键词: Adaptive Immune System; Antibiotic Resistance; Archaea; Bacteria; Bacteriophages; Clustered Regularly Interspaced Short Palindromic Repeats; Complex; Creativeness; DNA; Development; Disease; Ecology; Equilibrium; Evolution; Genes; Genetic; Genetic Variation; Genome engineering; Goals; Guide RNA; Immune system; Infection; Invaded; Mediating; Molecular Biology; Molecular Medicine; Nucleic Acids; Organism; Pathogenesis; Phylogenetic Analysis; Planets; Play; Process; Proteins; Research; Role; Sampling; Small RNA; Source; System; Viral; Virulence; Virus; Virus Diseases; Work; cell community; cell type; genetic element; human microbiota; innovation; insight; interest; mortality; nuclease; preservation; public health relevance; tool; trait

PROJECT SUMMARY Viruses are generally considered to be agents of destruction that must be efficiently eliminated by the host for self-preservation. However, viruses are also the largest reservoir of genetic diversity on the planet, and viral infections (estimated 1023 infections per second) are a primary mechanism for delivering new genes to naïve hosts. Thus, viruses have a complex role in the process of evolution, being both a major source of disease and mortality, while simultaneously presenting the cellular community with new opportunities for genetic innovation. In bacteria, viruses (i.e., phages) are major purveyors of genes that confer virulence and antibiotic resistance, and thus play a major role in the evolution of bacterial pathogenesis. The long-term goal of our research is to understand the impact of phage defense systems on the evolution and ecology of human-associated microbial communities. We are interested in understanding the dynamic processes that balance host preservation (defense from lethal infection) with the advantages of sampling foreign DNA for selectively advantageous traits. Specifically, the work outlined in this proposal is aimed at determining the mechanisms of two evolutionarily distinct immune systems that both rely on small RNA or small DNA guides for sequence-specific recognition of invading genetic elements. The proposal is divided into two projects, with an eye toward developing new tools for applications in molecular biology and medicine. Project 1 focuses on understanding the phylogenetic and functional diversity of phage encoded anti-CRISPRs that suppress CRISPR-mediated adaptive immune systems. Project 2 aims to understand the functional diversity of Argonaute proteins in bacteria and archaea. Results from this research will provide mechanistic insights that contribute to our long-term goal and have significance implications in the near-term application of these emerging tools for precise genome engineering.

项目概要 病毒通常被认为是破坏剂，必须被宿主有效地消除才能发挥作用。 然而，病毒也是地球上最大的遗传多样性储存库。 感染（估计每秒 1023 次感染）是向幼稚者传递新基因的主要机制 因此，病毒在进化过程中发挥着复杂的作用，既是疾病的主要来源，又是宿主的主要来源。 死亡率，同时为细胞界提供遗传创新的新机会。 在细菌中，病毒（即噬菌体）是赋予毒力和抗生素抗性的基因的主要提供者， 从而在细菌发病机制的进化中发挥重要作用。我们研究的长期目标是 了解噬菌体防御系统对人类相关微生物的进化和生态的影响 我们有兴趣了解平衡宿主保护的动态过程。 （防御致命感染）具有通过外源 DNA 进行选择性优势特征采样的优点。 具体来说，该提案中概述的工作旨在确定两种进化的机制 不同的免疫系统都依赖小RNA或小DNA指导来进行序列特异性识别 该提案分为两个项目，着眼于开发新工具。 用于分子生物学和医学的应用项目 1 侧重于了解系统发育和 噬菌体编码的抗 CRISPR 抑制 CRISPR 介导的适应性免疫的功能多样性 项目 2 旨在了解细菌和古细菌中 Argonaute 蛋白的功能多样性。 这项研究的结果将提供有助于我们长期目标的机制见解，并具有 这些新兴工具对精确基因组工程的近期应用具有重要意义。