Interrogating the contributions of novel immune systems to anti-phage defense in their native bacterial hosts
探究新型免疫系统对其天然细菌宿主的抗噬菌体防御的贡献
基本信息
- 批准号:465069819
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Priority Programmes
- 财政年份:
- 资助国家:德国
- 起止时间:
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Bacteria and phages have been locked in an evolutionary arms race for billions of years, with phages devising new offensive strategies and bacteria mounting countering defenses. Bacteria were long thought to possess three principal systems that confer antiviral defense: restriction-modification systems, CRISPR-Cas systems, and abortive infection systems. However, recent work has begun to reveal a far larger and more diverse repertoire of defense systems present throughout the bacterial world. Interrogating these systems and their contributions to antiviral defense represents the next major challenge to better understand bacterial-phage interactions and their impact on the environment and our resident microbiomes. To date, the few characterized examples of these novel defense systems involved biochemical studies or heterologous expression in standard laboratory strains. In contrast, defense systems are often integrated within the physiology of their host and co-exist with other present defense systems. What remains unclear is how these defense systems function in their natural context and the level of protection conferred by these systems versus the other resident defenses. Here, we propose to elucidate the antiviral properties of recently discovered defense systems in strains harboring these systems naturally. We have selected Zorya II as a compelling case study, as this system is widely prevalent in bacteria and encodes multiple proteins with unknown functions. Critically, these systems are found in numerous culturable, sequenced, and commercially-available strains of Escherichia coli possessing other defense systems, simplifying the interrogation of Zorya II in its natural context. Our operating hypothesis is that Zorya II elicits cell suicide through chromosomal destruction and provides a non-redundant layer of defense that further protects the bacterial population from phage infection. To test this hypothesis, we will pursue the following two research objectives: Objective 1: Elucidate how Zorya II achieves immune defense. Objective 2: Determine the unique contributions of Zorya II to antiviral defense.These objectives are supported by extensive preliminary data and the PI’s unique expertise in bacterial defense systems, genome editing, and cell-free systems. If successful, the proposed work will provide a mechanistic description of how a novel defense system contributes to antiviral defense in its native host. Such insights would directly support the mission of SPP 2330 by establishing new concepts and mechanisms for antiviral defense in bacteria.
数十亿年来,细菌和细菌一直处于进化的军备竞赛中,细菌设计了新的进攻策略,细菌则建立了反击防御。长期以来,细菌被认为拥有三个赋予抗病毒防御的主要系统:限制修饰系统,CRISPR-Cas系统和流产感染系统。然而,最近的工作已经开始揭示整个细菌世界中存在的更大,更多样化的防御系统。询问这些系统及其对抗病毒防御的贡献代表了下一个重大挑战,以更好地了解细菌-噬菌体相互作用及其对环境和我们的居民微生物组的影响。到目前为止,这些新的防御系统的几个特征的例子涉及生化研究或异源表达在标准的实验室菌株。相反,防御系统通常整合在宿主的生理学中,并与其他现有的防御系统共存。目前尚不清楚的是,这些防御系统如何在其自然环境中发挥作用,以及这些系统与其他居民防御系统相比所提供的保护水平。在这里,我们建议阐明最近发现的防御系统的抗病毒特性的菌株自然窝藏这些系统。我们选择Zorya II作为一个令人信服的案例研究,因为该系统在细菌中广泛存在,并编码多种功能未知的蛋白质。重要的是,这些系统存在于许多可培养的、测序的和商业上可获得的大肠杆菌菌株中,这些菌株具有其他防御系统,简化了Zorya II在其自然环境中的询问。我们的操作假设是,Zorya II通过染色体破坏促进细胞自杀,并提供了一个非冗余的防御层,进一步保护细菌种群免受噬菌体感染。为了验证这一假设,我们将追求以下两个研究目标:目标1:阐明Zorya II如何实现免疫防御。 目标二:确定Zorya II对抗病毒防御的独特贡献。这些目标得到了广泛的初步数据和PI在细菌防御系统,基因组编辑和无细胞系统方面的独特专业知识的支持。如果成功的话,这项工作将提供一个新的防御系统如何在其天然宿主中有助于抗病毒防御的机制描述。这些见解将通过建立细菌抗病毒防御的新概念和机制,直接支持SPP 2330的使命。
项目成果
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Professor Dr. Chase Beisel其他文献
Professor Dr. Chase Beisel的其他文献
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{{ truncateString('Professor Dr. Chase Beisel', 18)}}的其他基金
Prevalence, formation, and function of “extraneous” CRISPR RNAs derived from the extra repeat in CRISPR arrays
源自 CRISPR 阵列中额外重复序列的“外来”CRISPR RNA 的普遍性、形成和功能
- 批准号:
468749960 - 财政年份:
- 资助金额:
-- - 项目类别:
Priority Programmes
Characterizing CRISPR-Cas systems with non-defensive functions
表征具有非防御功能的 CRISPR-Cas 系统
- 批准号:
405891106 - 财政年份:
- 资助金额:
-- - 项目类别:
Priority Programmes
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