The Genetic Architecture of Maternal Supression of Symbionts

母体抑制共生体的遗传结构

• 批准号: 1456778
• 负责人: Seth Bordenstein
• 金额: $ 95.75万
• 依托单位: Vanderbilt University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1456778&HistoricalAwards=false
• 关键词: Genetic; Architecture; Maternal; Supression; Symbionts

At the turn of the 20th century, biologists asserted that babies develop within a sterile womb and acquire their initial bacteria from the environment. While this paradigm is under preliminary reconsideration today in light of new technologies and analyses, comparative studies of animals have long held that maternal provisioning of bacteria to offspring is widespread, spanning the base of the animal kingdom to vertebrates. Moreover, such bacteria are not simply innocuous passengers. They impart vital consequences to animal health and disease, and they have their own microbial interests, namely their propagation from mother to the next generation. In this context, there is a biological conundrum between host and maternally transmitted bacteria. High loads of bacteria can lead to pathogenesis in the animal offspring while low concentrations can lead to loss of the bacteria. Balancing these opposing outcomes in the middle is one possible way to reconcile the extremes. Thus, the critical biological question is how are the concentrations of maternally transmitted bacteria regulated? Using a preeminent animal-microbe model, the investigators will genetically test the hypotheses that (i) animal hosts express multiple (rather than single) genes to control the concentrations of maternally transmitted bacteria (ii) when these genes are disrupted from their normal functions, the bacterial densities transmitted to the offspring will increase and (iii) these genes control the bacteria by preventing them from entering the developing offspring and repressing their replication. This project will be the first study to deploy a unique genetic analysis that characterizes the animal genes that keep bacterial densities in check. The Principal Investigator will direct a one-week workshop for pre-service teachers (college students working towards a degree in education) based on the premise that the earlier that teachers participate in "discovery science", the more likely they will feel comfortable using it in the classrooms. The researchers will also partner with the School for Science and Math at Vanderbilt to develop a Community Engaged Research Project in which Nashville high school students transfer experiential learning from the research lab back to their classrooms to engage in the process of cooperative and peer-to-peer learning for science- and technology-related investigations.The majority of animal species harbor maternally-transmitted bacteria, yet little is known about the genetic and molecular mechanisms that the animal and bacteria use to achieve maternal transmission. For symbionts transmitted via the germ-line, bacterial density can critically influence transmission efficiency and penetrance of symbiotic traits induced by the symbiont. This research begins the first forward-genetic investigation of host genes that regulate densities of Wolbachia pipientis. The genus Wolbachia is a model endosymbiont because it occurs in more animal species than any other bacterium on the planet, and it can range from a beneficial symbiont in filarial nematodes, a parasitic manipulator of arthropod reproduction, to the main inflammatory agent of human filarial diseases. However, despite infection's prevalence, few host-Wolbachia interactions have been identified that control their densities. As a model host with genetic tools, the Nasonia parasitoid wasp genus is comprised of several closely related species that harbor unique strains of maternally-transmitted Wolbachia in their reproductive tissues. Transfer of these Wolbachia strains between the interfertile Nasonia species can result in dramatic changes in infection titers and tissue tropism. Specifically, the wVitA strain maintains a low infection density in its natural host, Nasonia vitripennis, but has a wider tissue tropism and stable infection density 100-fold higher in the naive host, Nasonia giraulti. Quantitative trait loci analyses specify that the regulation of the low wVitA density maps to three N. vitripennis chromosomal regions. This host regulation acts dominantly through a maternal effect - the mother determines the densities of her offspring. Thus, the central hypothesis of this research project is that multiple genes involved in host innate immunity and/or oogenesis act maternally to regulate Wolbachia densities in offspring. The goal of this project is to utilize an unprecedented interspecific difference in Wolbachia titers to identify the numbers and types of host genes that regulate Wolbachia densities, their additive and epistatic interactions, and their effects on Wolbachia localization and proliferation during oogenesis.

二十世纪之交，生物学家断言，婴儿在无菌子宫内发育，并从环境中获得最初的细菌。虽然今天根据新技术和分析对这一范式进行了初步重新考虑，但对动物的比较研究长期以来一直认为，母体向后代提供细菌的现象很普遍，从动物界一直到脊椎动物。此外，这些细菌不仅仅是无害的乘客。它们对动物健康和疾病产生至关重要的影响，并且它们有自己的微生物利益，即它们从母亲到下一代的繁殖。在这种情况下，宿主和母体传播的细菌之间存在生物学难题。高浓度的细菌会导致动物后代发病，而低浓度的细菌会导致细菌损失。 在中间平衡这些相反的结果是调和极端的一种可能方法。因此，关键的生物学问题是如何调节母源传播细菌的浓度？使用卓越的动物微生物模型，研究人员将从基因角度测试以下假设：（i）动物宿主表达多个（而不是单个）基因来控制母体传播的细菌的浓度（ii）当这些基因的正常功能受到破坏时，传播给后代的细菌密度将会增加，以及（iii）这些基因通过阻止细菌进入发育中的后代来控制细菌 并抑制它们的复制。 该项目将是第一个采用独特的遗传分析来表征控制细菌密度的动物基因的研究。首席研究员将为职前教师（正在攻读教育学位的大学生）举办为期一周的研讨会，其前提是教师越早参与“发现科学”，他们就越有可能在课堂上使用它。研究人员还将与范德比尔特科学与数学学院合作开发一个社区参与研究项目，纳什维尔高中学生将研究实验室的体验式学习转移回课堂，参与科学和技术相关研究的合作和同伴学习过程。大多数动物物种都含有母源传播的细菌，但人们对动物和细菌使用的遗传和分子机制知之甚少。 从而实现母婴传播。对于通过种系传播的共生体，细菌密度可以严重影响共生体诱导的共生性状的传播效率和外显率。这项研究开始了对调节 Wolbachia pipientis 密度的宿主基因的首次正向遗传学研究。沃尔巴克氏菌属是一种模型内共生体，因为它比地球上任何其他细菌都存在于更多的动物物种中，而且它的范围可以从丝虫线虫中的有益共生体、节肢动物繁殖的寄生操纵者，到人类丝虫疾病的主要炎症因子。然而，尽管感染很普遍，但很少有宿主与沃尔巴克氏体相互作用能够控制其密度。作为具有遗传工具的模型宿主，Nasonia 寄生蜂属由几个密切相关的物种组成，这些物种在其生殖组织中含有独特的母源传播的沃尔巴克氏体菌株。这些沃尔巴克氏体菌株在不育的 Nasonia 物种之间转移可能会导致感染滴度和组织向性发生巨大变化。具体来说，wVitA菌株在其天然宿主Nasonia vitripennis中保持较低的感染密度，但在幼稚宿主Nasonia giraulti中具有更广泛的组织向性和稳定的感染密度高100倍。数量性状位点分析表明，低 wVitA 密度的调节映射到三个 N. vitripennis 染色体区域。这种宿主调节主要通过母体效应发挥作用——母亲决定其后代的密度。因此，该研究项目的中心假设是，参与宿主先天免疫和/或卵子发生的多个基因通过母体作用来调节后代中沃尔巴克氏体的密度。该项目的目标是利用沃尔巴克氏体滴度前所未有的种间差异来确定调节沃尔巴克氏体密度的宿主基因的数量和类型、它们的加性和上位相互作用，以及它们对卵子发生过程中沃尔巴克氏体定位和增殖的影响。