Cellular mechanisms of endosymbiont transmission between host generations

宿主世代之间内共生体传播的细胞机制

• 批准号: 10667800
• 负责人: Shelbi Lianne Russell
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667800
• 关键词: Agriculture; Antibodies; Arthropods; Award; Bacteria; Bioinformatics; Biological Models; Biology; Candidate Disease Gene; Carbon; Career Transition Award; Cell Culture System; Cell Line; Cell physiology; Cells; Cellular biology; Chloroplasts; Communities; Complex; Conflict (Psychology); Data Set; Development; Diet; Disease Vectors; Doctor of Philosophy; Dominant-Negative Mutation; Drosophila genus; Drosophila melanogaster; Ecosystem; Ensure; Environment; Epidemic; Equilibrium; Eukaryota; Evolution; Exhibits; Funding; Future; Generations; Genes; Genome; Genomics; Horizontal Disease Transmission; Human; In Vitro; Individual; Infection; Inherited; Insecta; Intuition; Kinesin; Label; Learning; Life Style; Light; Mediating; Medicine; Methodology; Methods; Microtubules; Mitochondria; Modeling; Molecular; Molecular Biology; Motor; National Institute of General Medical Sciences; Nature; Nematoda; Nitrogen; Oogenesis; Organelles; Organism; Outcome; Parents; Pathogenicity; Pathway interactions; Phase; Plants; Process; Proteins; Recording of previous events; Reproduction; Research; Resistance; Resources; Source; Symbiosis; System; Techniques; Testing; Time; United States National Institutes of Health; Vent; Vertical Disease Transmission; Western Blotting; Wolbachia; Work; X-Ray Crystallography; base; career; cell motility; endosymbiont; feeding; fly; in vivo; insight; knock-down; microbial; mutualism; novel; pathogen; skills; symbiont; tool; trait; transmission process; vector control

Shelbi L Russell Project Summary Bacterial symbionts are ubiquitous among eukaryotes and are responsible for some of the most radical lifestyles in the natural world. For example, microbial symbiosis enables hydrothermal vent ecosystems to subsist on inorganic energy and carbon sources and plant-feeding insect communities to thrive on nitrogen-deficient diets. Often living with one partner inside the other, these associations require complex cellular mechanisms to ensure that conflict does not arise between host and symbiont. Reliable transmission mechanisms to reach new hosts are vital to stabilizing associations over evolutionary time. However, very little is known about the molecular mechanisms underlying these processes because the majority of endosymbionts are unculturable, and often the hosts are as well. Here, I propose to use ​Drosophila​ fruit flies and their ​Wolbachia​ endosymbionts as models for understanding host-symbiont interactions and the molecular mechanisms mediating symbiont transmission. ​Wolbachia ​is one of the most abundant intracellular symbionts in nature by virtue of its ability to associate with the host germline and manipulate host reproduction for vertical transmission. It is also occasionally beneficial to its hosts by promoting pathogen resistance and performing necessary cellular tasks. These traits make this bacterium useful for applications in disease vector control. While Wolbachia i​ s faithfully inherited through the germline in all associations examined to date, horizontal transmission between contemporary hosts, of the same and different species, is common throughout their evolutionary history and can be recapitulated in the lab. During the K99 funding period, I will use the ​D. melanogaster​-​Wolbachia ​system to characterize and identify the genes/pathways necessary for endosymbiont transmission within and between cells. This will be accomplished in two aims: In Aim 1, I will use ​Wolbachia​-infected ​Drosophila c​ ell lines to explore the functional mechanisms and evolutionary outcomes of mixed strain infections. In Aim 2, I will characterize the symbiont and host linker proteins ​Wolbachia ​uses for KHC-dependent microtubule-based motility. I will use the results of this work during the R00 phase to explore how intracellular and cell-to-cell transfer mechanisms integrate in the whole fly for vertical transmission through the germline and horizontal transmission between host individuals. Thus, this work will provide mechanistic insight into the transmission strategies employed by endosymbionts around the world.

Shelbi L Russell 项目摘要 细菌共生体在真核生物中无处不在，并且是最多的 例如，自然世界中的无激进生活。 排气生态系统以生存无机能源和碳源和植物喂养昆虫 社区以氮缺陷饮食壮成长。 这些关联需要复杂的蜂窝机制，以确保不出现冲突 在主机和共生体之间。 在进化时间上稳定关联。 由于大多数内共生体是 不可耕种，通常也是主人。 他们的Wolbachia内共生体作为用于理解宿主 - 伴侣相互作用和您的模型 介导共生传播的分子机制。 自然界中丰富的细胞内共生体具有与宿主相关的能力 种系和操纵宿主繁殖以进行垂直传播。 通过促进病原体抗性并执行必要的细胞，有益于宿主 这些特征使该细菌适用于疾病载体的应用 沃尔巴奇（Wolbachia 相同物种和不同物种之间的当代寄主之间的水平传播是 在整个进化史上常见 K99资金期，我将使用D. Melanogaster-Wolbachia系统来表征和 确定内共生传播WITIN和细胞之间所需的基因/途径。 这将在两个目标中访问：在AIM 1中，我将使用沃尔巴基亚感染的果蝇C la c ll 线以探索混合应变的功能机制和进化结果 感染。 基于KHC依赖的微管运动。 阶段探索细胞内和细胞向细胞转移机制如何整体整合 用于通过种系的垂直传输和宿主之间的水平传播 个人。 由世界各地的内共生菌雇用。