CAREER: PHIRED UP: Phage-Host Interactions integrated into Research on Epiphytic Ecology and Disease using Undergraduate Participation

职业：PHIRED UP：利用本科生参与将噬菌体-宿主相互作用纳入附生生态学和疾病研究

• 批准号: 1942881
• 负责人: Britt Koskella
• 金额: $ 57.5万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1942881&HistoricalAwards=false
• 关键词: CAREER; PHIRED; UP; Phage; Host

Bacteriophages, the viruses that infect bacteria, are the most ubiquitous and diverse entities on Earth, infecting the vast majority of bacteria. Lytic phages that infect and kill their bacterial host cells can alter bacterial community profiles (who is there and at what density) as well as competitive dynamics among strains, with clear potential to shape host-associated microbiomes. Phages can also impact the outcome of eukaryotic disease, either directly by infecting and killing bacterial pathogens within hosts or indirectly by changing the microbiome, which is known to play a role in many plant and animal diseases. This project uses monthly sampling of pear trees from an urban environment (Berkeley city) across multiple years and large-scale genomic sequencing efforts to determine the role phages play in Fire Blight disease, an agriculturally relevant disease of many orchard species. By fully integrating undergraduate research using a peer mentoring ladder, this exploration of phage infection and community dynamics in leaf-associated bacterial microbiomes will help identify both which bacteria are naturally targeted by phages, and how these phages shape change in pathogen densities and microbiome community composition. Bacterial and phage culturing approaches will be combined with a multi-omics analysis of the pear tree microbiome to fully elucidate how phages adapt to bacteria in nature and how such adaptation impacts the microbiome in health and disease. The long-term aim is to use these data on natural phage-mediated selection to determine if and how phages can be used to reshape microbial communities and prevent disease. The evolutionary interactions of phages and their bacterial hosts has been studied extensively in the lab, but few studies have examined these dynamics in nature. The project integrates a four module undergraduate research program with high-throughput, culture independent sequencing of both bacterial and viral communities to examine the role of phages in bacterial community turnover and disease using a novel Pear Tree disease system (Callery ‘Bradford’ pear trees infected with the agriculturally relevant pathogen Erwinia amylovora). Through the tight integration of teaching and research, the combination of culture-dependent screening and culture-independent ‘omics’ approaches will allow for tracking of bacteria-phage dynamics over both short (monthly) and long (yearly) time scales. Overall, the project aims to build an unparalleled temporal and spatial dataset on phage host range with which to examine the role of phages (both lytic and temperate) in bacterial community assembly, stability, and pathogen invasion. The project uses both classic empirical approaches to study the strength and scale of phage adaptation and new computational approaches to predict how phages shape microbial networks. The data generated will offer unprecedented insight into bacteria-phage dynamics in nature and viral host range evolution in a complex community setting. The research further develops basic understanding of plant microbiomes and viromes, and will also support the development of a new disease ecology model system that is both amenable to undergraduate training in the emerging microbiome field and unique in its potential to gain insight into virome-microbiome interactions in both health and disease.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

噬菌体，感染细菌的病毒，是地球上最普遍和最多样化的实体，感染绝大多数细菌。感染并杀死其细菌宿主细胞的溶解噬菌体可以改变细菌群落概况（谁在那里，密度是多少）以及菌株之间的竞争动态，具有明显的塑造宿主相关微生物组的潜力。噬菌体还可以影响真核疾病的结果，要么直接通过感染和杀死宿主内的细菌病原体，要么间接通过改变微生物组，这在许多植物和动物疾病中发挥作用。该项目使用多年来每月对城市环境（伯克利市）的梨树进行采样，并进行大规模基因组测序，以确定噬菌体在火疫病中的作用，这是许多果园物种的农业相关疾病。通过充分整合本科生研究，利用同侪指导阶梯，对叶片相关细菌微生物组中噬菌体感染和群落动态的探索将有助于确定哪些细菌是噬菌体的天然目标，以及这些噬菌体如何改变病原体密度和微生物群落组成。细菌和噬菌体培养方法将与梨树微生物组的多组学分析相结合，以充分阐明噬菌体如何适应自然界中的细菌以及这种适应如何影响健康和疾病中的微生物组。长期目标是利用这些自然噬菌体介导选择的数据来确定噬菌体是否以及如何用于重塑微生物群落和预防疾病。噬菌体及其细菌宿主的进化相互作用已经在实验室中进行了广泛的研究，但很少有研究在自然界中检测这些动力学。该项目将四个模块的本科研究项目与高通量、培养独立的细菌和病毒群落测序结合起来，利用一种新的梨树疾病系统（Callery ‘ Bradford ’梨树感染了与农业相关的淀粉Erwinia amylovora），研究噬菌体在细菌群落更替和疾病中的作用。通过教学和研究的紧密结合，培养依赖筛选和培养独立“组学”方法的结合将允许在短期（每月）和长期（每年）的时间尺度上跟踪细菌噬菌体动态。总体而言，该项目旨在建立一个无与伦比的噬菌体宿主范围的时空数据集，以研究噬菌体（裂解和温带）在细菌群落组装，稳定性和病原体入侵中的作用。该项目使用经典的经验方法来研究噬菌体适应的强度和规模，并使用新的计算方法来预测噬菌体如何形成微生物网络。所产生的数据将为自然界中的噬菌体动力学和复杂社区环境中的病毒宿主范围进化提供前所未有的见解。该研究进一步发展了对植物微生物组和病毒组的基本认识，也将支持一种新的疾病生态学模型系统的发展，该模型系统既适合新兴微生物组领域的本科培训，又具有独特的潜力，可以深入了解病毒组-微生物组在健康和疾病中的相互作用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Understanding the Impacts of Bacteriophage Viruses: From Laboratory Evolution to Natural Ecosystems

了解噬菌体病毒的影响：从实验室进化到自然生态系统

• DOI: 10.1146/annurev-virology-091919-075914
• 发表时间: 2022
• 期刊: Annual Review of Virology
• 影响因子: 11.3
• 作者: Koskella, Britt;Hernandez, Catherine A.;Wheatley, Rachel M.
• 通讯作者: Wheatley, Rachel M.