CRISPR Capture, Destroy, and Counter-Attack Mechanisms

CRISPR 捕获、破坏和反击机制

• 批准号: 10627779
• 负责人: MICHAEL P TERNS
• 金额: $ 56.8万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10627779
• 关键词: Adaptive Immune System; Antibiotic Resistance; Back; Bacteria; Basic Science; Biochemical; Biotechnology; CRISPR/Cas technology; Clustered Regularly Interspaced Short Palindromic Repeats; Diagnosis; Gene Expression; Genetic; Genetic Diseases; Genome; Human; Human Genetics; Immune; Immune mediated destruction; Immune system; Immunity; Knowledge; Mediating; Medical Research; Molecular; Organism; Pathway interactions; Proteins; RNA; Research; System; Technology; Viral; Viral Physiology; Virus; Virus Diseases; Work; antiviral immunity; fighting; genome editing; human disease; improved; innovation; insight; nuclease; pathogenic bacteria; pathogenic virus; programs; tool

Project Summary CRISPR-Cas adaptive immune systems are deployed by prokaryotic organisms to protect them from potential lethal infection by viruses. As a counter-defense strategy, certain viruses produce anti-CRISPR (ACR) proteins capable of inactivating CRISPR-mediated, anti-viral immunity. Diverse CRISPR-Cas systems function by capturing short viral sequences within the CRISPR locus of the host genome and using expressed crRNAs and associated Cas nucleases for viral recognition and destruction. The identities and functions of viral ACRs in subverting distinct CRISPR-Cas systems are only just now being revealed. The primary objectives of our research program are: 1) to understand the molecular basis of mechanisms underlying both host CRISPR-Cas immune pathways and anti-CRISPR activities of viruses and 2) to exploit knowledge gained to contribute and improve CRISPR-based applications. Using an established and powerful combination of molecular, genetic, structural and biochemical approaches, with invaluable contributions from a team of superb collaborators, we will continue to work to dissect pathways and delineate molecular mechanisms governing diverse CRISPR-Cas systems. Furthermore, we will gain key insight on ACR-mediated mechanisms used by viruses to thwart CRISPR immunity. Innovative CRISPR-based tools and technologies are providing transformative advances in basic and medical research. The knowledge gained by our research will contribute directly to ongoing efforts aimed at exploiting diverse CRISPR-Cas systems as powerful research tools (e.g. for genome editing and controlled gene expression, to selectively detect and target human viral and bacterial pathogens, and for limiting the spread of antibiotic resistance). Moreover, understanding the detailed modes of action of diverse ACRs is necessary for establishing ACRs as important new research tools for selective and safe utilization of different CRISPR-based technologies.

项目摘要 CRISPR-CAS适应性免疫系统由原核生物部署，以保护它们免受潜在 病毒致死感染。作为一种反防卫策略，某些病毒产生抗危机（ACR）蛋白 能够失活CRISPR介导的抗病毒免疫。不同的CRISPR-CAS系统功能 在宿主基因组的CRISPR基因座中捕获短病毒序列，并使用表达的CRRNA和 相关的CAS核酸酶，用于病毒识别和破坏。病毒ACR的身份和功能 颠覆了不同的CRISPR-CAS系统，直到现在才被揭示。我们的主要目标 研究计划是：1）了解两个宿主CRISPR-CAS基础机制的分子基础 病毒的免疫途径和抗Crispr活性以及2）利用获得的知识来贡献和 改善基于CRISPR的应用程序。使用分子，遗传，既定强大的组合 结构和生化方法，以及一支精湛的合作者团队的宝贵贡献，我们 将继续努力剖析途径，并描述有关多种CRISPR-CAS的分子机制 系统。此外，我们将获得对病毒阻碍ACR介导的机制的关键见解 CRISPR免疫。创新的基于CRISPR的工具和技术正在提供变革性的进步 基础和医学研究。我们的研究获得的知识将直接为持续的努力做出贡献 旨在利用各种CRISPR-CAS系统作为强大的研究工具（例如，用于基因组编辑和 受控的基因表达，有选择地检测和靶向人类病毒和细菌病原体，以及 限制抗生素耐药性的扩散）。此外，了解各种各样的详细行动方式 ACRS对于建立ACR作为重要的新研究工具是必要的，以选择性和安全利用 不同的基于CRISPR的技术。