BBSRC-NSF/BIO:Collaborative Research: Phage host range evolution in spatially structured microbiomes

BBSRC-NSF/BIO：合作研究：空间结构微生物组中的噬菌体宿主范围进化

• 批准号: 2017879
• 负责人: Carey Nadell
• 金额: $ 30万
• 依托单位: Dartmouth College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2017879&HistoricalAwards=false
• 关键词: BBSRC; NSF; BIO; Collaborative; Research

Bacteriophages, the viral parasites of bacteria, are major agents of bacterial death in microbial communities or microbiomes. Previous work has shown that phage host range, the type of bacteria a given phage can successfully infect, can evolve rapidly. This evolution alters the impact that phage have on the composition and function of microbial communities. However, this previous work has focused on bacteria growing in well-mixed conditions while many bacteria in microbiomes exist in aggregations known as biofilms. In biofilms not only is the spatial arrangement of bacteria different, but also their physiology or lifestyle. In this project, which is a collaboration between researchers at the University of Minnesota (US), Dartmouth College (US) and the University of Exeter (UK), research will pair state of the art computer simulations with cutting edge experimental approaches to develop and test theory for predicting the impact that bacteriophage have on bacterial communities. This work will improve our ability to manage microbial communities that are vital for human health, agricultural production, and industrial applications. The project will help train the next generation of scientific leaders by working with postdoctoral researchers and graduate students to carry out the research. Additionally, it will develop teaching modules to engage high school students with the power of computational biology, preparing them to drive the bio-economy of the future.Despite the abundance of phage and the prevalence of biofilm growth, little is known about the interaction between phage and biofilms. Specifically, there has been a paucity of investigation on how biofilms influence the evolution of phage host range. In addition to developing knowledge on a process that is critical to understanding microbiome behavior, the proposed work will also improve understanding of the evolution of generalist and specialist strategies more broadly. It will connect individual parasite movement to the dynamics of infection waves in heterogeneous environments. Additionally, it will quantify how host heterogeneity that arises from biotic and abiotic factors alters the evolution of parasite host range. The work will integrate a variety of models that span different length scales, with a powerful model system involving Escherichia coli and the bacteriophage T7. The research will develop and test theory to understand the impact of spatial organization, including the abundance of different hosts in a structured environment, the size of patches of hosts and the connectivity of these patches. The research will also develop and test theory to understand the consequences of bacterial matrix production, metabolic heterogeneity of hosts, and host mixing in biofilms. This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.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.

噬菌体是细菌的病毒寄生物，是微生物群落或微生物组中细菌死亡的主要媒介。先前的工作表明，噬菌体宿主范围，即给定噬菌体可以成功感染的细菌类型，可以迅速进化。这种进化改变了噬菌体对微生物群落的组成和功能的影响。然而，这项先前的工作集中在细菌在混合良好的条件下生长，而微生物组中的许多细菌以称为生物膜的聚集体存在。在生物膜中，不仅细菌的空间排列不同，而且它们的生理或生活方式也不同。在这个项目中，这是明尼苏达大学（美国），达特茅斯学院（美国）和埃克塞特大学（英国）的研究人员之间的合作，研究将最先进的计算机模拟与尖端的实验方法配对，以开发和测试预测噬菌体对细菌群落影响的理论。这项工作将提高我们管理对人类健康、农业生产和工业应用至关重要的微生物群落的能力。该项目将通过与博士后研究人员和研究生合作开展研究，帮助培养下一代科学领导人。此外，它还将开发教学模块，让高中生接触到计算生物学的力量，为他们推动未来的生物经济做好准备。尽管噬菌体丰富，生物膜生长普遍，但人们对噬菌体和生物膜之间的相互作用知之甚少。具体而言，一直缺乏调查如何生物膜影响噬菌体宿主范围的演变。除了开发对理解微生物组行为至关重要的过程的知识外，拟议的工作还将更广泛地提高对通才和专家策略演变的理解。它将把单个寄生虫的运动与异质环境中感染波的动力学联系起来。此外，它将量化宿主异质性，生物和非生物因素引起的改变寄生虫宿主范围的演变。这项工作将整合跨越不同长度尺度的各种模型，以及涉及大肠杆菌和噬菌体T7的强大模型系统。该研究将开发和测试理论，以了解空间组织的影响，包括结构化环境中不同主机的丰度，主机补丁的大小以及这些补丁的连接性。该研究还将开发和测试理论，以了解细菌基质生产，宿主代谢异质性和生物膜中宿主混合的后果。这个美国/英国合作项目由美国国家科学基金会和英国生物技术和生物科学研究理事会支持。这个奖项反映了NSF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。