The Genetic Architecture of Maternal Supression of Symbionts

在20世纪之交，生物学家断言，婴儿在不育的子宫中发育，并从环境中获得最初的细菌。虽然随着新技术和新分析的出现，这一模式今天正在进行初步的重新考虑，但对动物的比较研究长期以来一直认为，从动物王国的基础到脊椎动物，母体向后代提供细菌的情况很普遍。此外，这种细菌对乘客来说并不是简单的无害。它们给动物健康和疾病带来重要后果，它们有自己的微生物利益，即它们从母亲传给下一代。在这种情况下，宿主和母体传播的细菌之间存在着一个生物学难题。高负荷的细菌会导致动物后代的致病，而低浓度的细菌会导致细菌的丧失。在中间平衡这些对立的结果，是调和极端的一种可能方式。因此，关键的生物学问题是如何调节经母体传播的细菌的浓度？使用卓越的动物-微生物模型，研究人员将从基因上测试以下假设：(I)动物宿主表达多个(而不是单一)基因来控制母源传播细菌的浓度；(Ii)当这些基因扰乱它们的正常功能时，传播给后代的细菌密度将增加；以及(Iii)这些基因通过阻止细菌进入发育中的后代并抑制它们的复制来控制细菌。这个项目将是第一个采用独特的基因分析的研究，该分析表征了控制细菌密度的动物基因。首席调查员将为职前教师(正在攻读教育学学位的大学生)主持一个为期一周的研讨会，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，在该项目中，纳什维尔的高中生将经验学习从研究实验室转移回教室，参与合作和对等学习的过程，进行与科学和技术相关的研究。大多数动物物种都有母体传播的细菌，但对动物和细菌用来实现母体传播的遗传和分子机制知之甚少。对于通过生殖系传播的共生菌，细菌密度对共生菌诱导的共生特性的传递效率和外显率有重要影响。这项研究开始了对调节沃尔巴克氏杆菌密度的宿主基因的第一次正向遗传学调查。沃尔巴克氏杆菌属是一种典型的内共生菌，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，它的范围从丝虫线虫中有益的共生体(节肢动物繁殖的寄生操纵者)到人类丝虫病的主要炎症因子。然而，尽管感染很普遍，但几乎没有发现控制其密度的宿主-沃尔巴克氏菌相互作用。作为一种具有遗传工具的模式寄主，纳斯尼亚寄生蜂属由几个密切相关的物种组成，这些物种在生殖组织中含有独特的母传沃尔巴克氏菌株。这些沃尔巴克氏菌株在干扰的纳西尼亚种之间的转移可以导致感染滴度和组织趋向性的巨大变化。具体地说，wVitA菌株在其自然宿主--玻璃新月球藻中保持了较低的感染密度，但在幼稚宿主--长春新月球藻中具有更广泛的组织趋向性和稳定的感染密度，高出100倍。数量性状基因座分析表明，低wVitA浓度的调控定位于三个拟南芥染色体区域。这种寄主调节主要通过母体效应发挥作用--母体决定其后代的密度。因此，本研究项目的中心假设是，参与宿主先天性免疫和/或卵子发生的多个基因对后代的沃尔巴克氏菌密度起母性调节作用。该项目的目标是利用沃尔巴克氏菌滴度的前所未有的种间差异来鉴定控制沃尔巴克氏菌密度的寄主基因的数量和类型，它们的相加和上位性相互作用，以及它们在卵子发生过程中对沃尔巴克氏菌定位和增殖的影响。

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.