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

噬菌体是细菌的病毒寄生虫，是微生物群落或微生物群中细菌死亡的主要原因。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，可以快速进化。这种进化改变了噬菌体对微生物群落组成和功能的影响。然而，这项先前的工作集中在混合良好的条件下生长的细菌，而微生物群中的许多细菌存在于被称为生物膜的聚集体中。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。在这个由明尼苏达大学(美国)、达特茅斯学院(美国)和埃克塞特大学(英国)的研究人员合作的项目中，研究将把最先进的计算机模拟与尖端的实验方法结合起来，以开发和测试理论来预测噬菌体对细菌群落的影响。这项工作将提高我们管理微生物群落的能力，这些微生物群落对人类健康、农业生产和工业应用至关重要。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袖。此外，它还将开发教学模块，让高中生学习计算生物学的力量，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，但对噬菌体和生物膜之间的相互作用知之甚少。具体地说，关于生物膜如何影响噬菌体宿主范围的进化的研究一直很少。除了开发关于对理解微生物组行为至关重要的过程的知识外，拟议的工作还将在更广泛的范围内提高对多面手和专家策略演变的理解。它将把个体寄生虫的运动与不同环境中感染波的动态联系起来。此外，它还将量化由生物和非生物因素引起的宿主异质性如何改变寄生虫宿主范围的进化。这项工作将整合跨越不同长度尺度的各种模型，以及一个涉及大肠杆菌和噬菌体T7的强大模型系统。这项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富度、主机斑块的大小以及这些斑块的连通性。这项研究还将开发和测试理论，以了解细菌基质产生、宿主的代谢异质性和宿主在生物膜中混合的后果。这一美英合作项目得到了美国国家科学基金会和英国生物技术和生物科学研究委员会的支持。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.