Establishing the genetic basis of symbiosis in an insect host

建立昆虫宿主共生的遗传基础

基本信息

批准号：
BB/S017534/1
负责人：
Gregory Hurst
金额：
$ 77.1万
依托单位：
University of Liverpool
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=BB%2FS017534%2F1
关键词：
Establishing genetic basis symbiosis insect

项目摘要

An animal body is habitat for billions of bacteria, which live in the gut and on the skin. These bacteria were long regard as passengers we called commensals - using the animal as a host, but not strongly affecting the biology of the animal. In contrast, we now recognise that these microbes are an important and active component of the individual - how an organism develops, its immunity and resistance to infection all misbehave when the microbiome is absent or depleted. In insects, symbiosis ('living together') is commonly even better established - microbial partners exist within the body of the insect, not just within the gut and upon skin surfaces. Further, they may be heritable- transmitted from a female to her progeny. These microbial partners define very important properties of the insect -the ability to utilize a plant as a pest; whether the insect can transmit pathogens onward to plants and animals; whether the individual is susceptible to viral/parasitic infection. These properties are exploitable - in Cairns, Australia, mosquitoes carrying a symbiotic microbe that prevents the transmission of dengue are released en masse to protect the residents from infection by dengue. We currently know little about how these symbionts work. One observation is that they commonly have degraded genomes - which predicts increased reliance on the genes remaining. In addition, the microbes have to deploy an array of genes to establish persistent symbiosis - a long life within the host. The first part of this project will examine how much of the genome is required for these functions. We will also ask if symbiosis is a 'redeployment' of pathogen systems, or whether novel mechanisms are involved. Beyond this, we will establish how symbiosis genes enable the microbe to complete their life cycle, and how they modify the biology of their host - in our case, showing male-limited pathogenesis (male-killing).The reason we have not been able to answer this question before is simple: adaptation to life within a host makes these bacteria very hard to study outside of the host. In this project, we will exploit a symbiosis where the microbe can be grown in culture, where we can alter the genetic constitution of the microbe and can re-introduce strains easily to the insect. We will use this system to test which aspects of the microbe's genome determine its ability to be symbiotic. We have created 10,000 strains of the bacterium Arsenophonus nasoniae, each with a different gene 'knocked out'. We will reintroduce these into the host insect (the tiny parasitic jewel wasp). We are interested in the strains that fail to establish a symbiosis - these will be ones where the gene in question is necessary for the bacteria to live in symbiosis. We will then explore how these genes aid in establishing a symbiotic life style. Further to this, we will identify the genes responsible for male-killing.In completing this analysis, we will achieve the first examination of the genes and systems that microbes require to live within an insect and modify its biology. In addition to the intrinsic scientific interest of the research, our findings will allow us to better exploit symbionts to improve human health and food supply. Our focal microbe is closely related to insect vectored plant pathogens that damage fruit plants, and other bacteria that are associated with poor honeybee health. More generally, the knowledge gained will allow us to better engineer novel host-symbiont combinations for pest and vector control, with the aim of improving agricultural yields and human health.

动物体内是数十亿细菌的栖息地，这些细菌生活在肠道和皮肤上。这些细菌长期以来被视为乘客，我们称之为共生体——以动物为宿主，但不会强烈影响动物的生物学。相比之下，我们现在认识到这些微生物是个体的重要且活跃的组成部分——当微生物组缺失或耗尽时，有机体如何发育、其免疫力和对感染的抵抗力都会出现问题。在昆虫中，共生（“共同生活”）通常更容易建立——微生物伙伴存在于昆虫体内，而不仅仅是肠道内和皮肤表面。此外，它们可能是可遗传的——从女性传给她的后代。这些微生物伙伴定义了昆虫非常重要的特性——利用植物作为害虫的能力；昆虫是否可以将病原体传播给植物和动物；个体是否易受病毒/寄生虫感染。这些特性是可以利用的——在澳大利亚凯恩斯，携带阻止登革热传播的共生微生物的蚊子被大规模释放，以保护居民免受登革热感染。目前我们对这些共生体如何运作知之甚少。一项观察结果是，它们的基因组普遍退化——这预示着它们对剩余基因的依赖会增加。此外，微生物必须部署一系列基因来建立持久的共生关系——在宿主体内延长寿命。该项目的第一部分将检查这些功能需要多少基因组。我们还将询问共生是否是病原体系统的“重新部署”，或者是否涉及新的机制。除此之外，我们将确定共生基因如何使微生物完成其生命周期，以及它们如何改变宿主的生物学——在我们的例子中，显示出雄性限制的发病机制（雄性致死）。我们无法做到这一点的原因之前回答这个问题很简单：对宿主体内生活的适应使得这些细菌很难在宿主之外进行研究。在这个项目中，我们将利用一种共生关系，使微生物可以在培养物中生长，我们可以改变微生物的遗传构成，并可以轻松地将菌株重新引入昆虫。我们将使用这个系统来测试微生物基因组的哪些方面决定其共生能力。我们已经培育出了 10,000 种纳索尼亚砷细菌菌株，每种菌株都有一个不同的基因被“敲除”。我们将把它们重新引入宿主昆虫（微小的寄生宝石黄蜂）中。我们对未能建立共生的菌株感兴趣——这些菌株中的基因对于细菌的共生生存是必需的。然后我们将探索这些基因如何帮助建立共生生活方式。除此之外，我们将确定导致雄性死亡的基因。在完成这项分析时，我们将首次检查微生物在昆虫体内生存并改变其生物学所需的基因和系统。除了研究的内在科学意义外，我们的研究结果将使我们能够更好地利用共生体来改善人类健康和粮食供应。我们的焦点微生物与损害果树的昆虫传播的植物病原体以及与蜜蜂健康状况不佳相关的其他细菌密切相关。更一般地说，所获得的知识将使我们能够更好地设计用于害虫和病媒控制的新型宿主共生组合，以提高农业产量和人类健康。