The impact of spatial structure of CRISPR-phage coevolution

CRISPR-噬菌体协同进化空间结构的影响

基本信息

批准号：
NE/S001921/1
负责人：
Edze Rients Westra
金额：
$ 56.96万
依托单位：
UNIVERSITY OF EXETER
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=NE%2FS001921%2F1
关键词：
impact spatial structure CRISPR phage

项目摘要

It is becoming increasingly clear that bacteriophage (phage) can play a key role in shaping microbial community composition and function. This project aims to study the importance of one of the most widespread immune mechanisms, known as CRISPR-Cas, for bacteria-phage interactions in natural environments. Nearly half of all bacteria encode CRISPR-Cas, and this immune system is therefore thought to be particularly important in determining the role of phage in regulating bacterial populations dynamics and evolution. In the face of bacteria that evolve CRISPR immunity, the importance of phage will strongly depend on whether or not it can coevolve to overcome immunity, which could subsequently lead to an arms race of defense and counter-defense. Although lab based studies frequently find that CRISPR resistant bacteria drive phage extinct, studies on wild bacterial populations support the idea that phage can coevolve with CRISPR in nature. We hypothesize that this discrepancy between CRISPR-phage coevolution in nature and the lab is due to the lack of ecological complexity in lab-based studies, which may be critical for coevolution to occur. By studying CRISPR-phage interactions in laboratory media and semi-natural environments we will be able to identify the factors that determine the importance and coevolutionary consequences of CRISPR-Cas immune mechanisms in nature.Our preliminary data and existing suggest that spatial structure will be a particularly important factor in determining whether or not phage can coevolve with CRISPR, but the underlying mechanism remains unclear. In the proposed study, we will examine this by generating novel theory and performing experimental tests both in laboratory media and in sterilized soil with different levels of spatial structure. Apart from making an important contribution to our fundamental understanding of CRISPR-phage coevolution in natural environments, this research can also provide important insights into the potential role that CRISPR-phage interactions play in the ecology and evolution of soil microbiomes. Soils remain the most poorly understood ecosystems on Earth, even though it has been estimated that the biological services that soils provide are worth more than $20 trillion globally and are critical for many processes that humans depend on, including the production of food and various compounds, the purification of water, disposal of waste and cycling of nutrients. In this study, we will use a systems biology approach where we will generate mathematical models that predict the effects of spatial structure for bacterial and phage evolution, their coexistence and coevolution. We will then test these predictions using laboratory evolution experiments, where we will tease apart the different effects of spatial structure on CRISPR-phage interactions in highly controlled environments. In the third objective, we will monitor CRISPR-phage coevolution in soil mesocosms containing different soils with different structural properties and examine CRISPR-phage coevolution across the different soils and under different mixing regimes. Altogether, the data from this research will help to understand how a simple ecological factor - spatial structure - impacts CRISPR-phage coevolution and therefore bacterial and phage population dynamics, which can have important consequences for ecosystem functioning. We will use a powerful combination of mathematics, molecular and evolutionary biology, and microbial ecology to resolve an important discrepancy between experimental and correlational studies on CRISPR-phage coevolution.

越来越清楚的是，噬菌体（噬菌体）可以在塑造微生物群落组成和功能中发挥关键作用。该项目旨在研究自然环境中最广泛的免疫机制之一（称为CRISPR-CAS）的重要性。因此，在所有细菌中，几乎一半编码CRISPR-CAS，因此该免疫系统被认为在确定噬菌体在调节细菌种群动力学和进化中的作用方面尤其重要。面对发展CRISPR免疫的细菌，噬菌体的重要性将在很大程度上取决于它是否可以共同克服免疫力，这可能会导致防御和防守型的军备竞赛。尽管基于实验室的研究经常发现CRISPR耐药细菌驱动噬菌体灭绝，但对野生细菌种群的研究支持了噬菌体可以与CRISPR相结合的想法。我们假设，自然界中的CRISPR-phage协同进化与实验室之间的这种差异是由于基于实验室的研究缺乏生态复杂性，这对于进化可能是至关重要的。通过研究实验室媒体和半自然环境中的CRISPR-page相互作用，我们将能够确定确定自然界CRISPR-CAS免疫机制的重要性和协同进化后果的因素。我们的初步数据和现有表明，空间结构将是确定或不确定CRIS PREVEL的一个特别重要的因素，而不是phage与CRISPR相辅相成，但仍有不稳定的机制，而无关紧要。在拟议的研究中，我们将通过在实验室培养基和具有不同空间结构水平的消毒土壤中产生新的理论和进行实验测试来研究这一点。除了对我们对自然环境中CRISPR-phage协同进化的基本理解做出重要贡献外，这项研究还可以为CRISPR-phage相互作用在土壤微生物组的生态学和进化中所发挥的潜在作用提供重要的见解。尽管已经估计，土壤仍然是地球上最知名的生态系统，尽管据估计，土壤提供的生物服务价值超过20万亿美元，并且对于人类依赖的许多过程至关重要，包括食物和各种化合物的产生，水的净化，净化水，浪费和营养循环的营养物质。在这项研究中，我们将使用一种系统生物学方法，在其中生成数学模型，以预测空间结构对细菌和噬菌体进化的影响，它们的共存和共同进化。然后，我们将使用实验室进化实验测试这些预测，在这里，我们将分开空间结构对高度控制环境中CRISPR-page相互作用的不同影响。在第三个目标中，我们将监测含有不同结构特性的不同土壤的土壤中的CRIS-PHAGE协同进化，并检查在不同土壤和不同混合方面的CRISPR-phage协同进化。总而言之，这项研究的数据将有助于了解简单的生态因素（空间结构）如何影响CRISPR -phage协同进化，从而影响细菌和噬菌体种群动力学，这可能对生态系统功能产生重要的后果。我们将使用数学，分子和进化生物学以及微生物生态学的有力组合来解决有关CRISPR-phage协同进化的实验和相关研究之间的重要差异。