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.

谢尔比·L·拉塞尔 项目摘要 细菌共生体在真核生物中普遍存在，并负责一些最重要的生物学过程。 自然界中的激进生活方式。例如，微生物共生使水热 喷口生态系统依靠无机能源和碳源以及食草昆虫生存 社区在氮缺乏的饮食中茁壮成长。常常是一个人住在另一个人的身体里， 这些关联需要复杂的细胞机制来确保冲突不会发生 宿主和共生体之间的联系到达新主机的可靠传输机制对于 在进化过程中稳定关联。然而，人们对这种分子结构知之甚少。 这些过程背后的机制，因为大多数内共生体是 没有文化，而且通常主人也是如此。在这里，我建议使用果蝇， 他们将沃尔巴克氏体内共生体作为理解宿主-共生体相互作用的模型， 介导共生体传递的分子机制。 沃尔巴克氏体是人类 由于其与宿主结合的能力，自然界中存在丰富的细胞内共生体 生殖系和操纵宿主生殖以进行垂直传播。也是偶尔 通过促进病原体抗性和进行必要的细胞增殖， 任务这些特性使该细菌可用于病媒控制。而 沃尔巴克氏体是忠实地通过生殖系遗传在所有协会检查日期， 同一物种和不同物种的当代宿主之间的水平传播， 在它们的进化史中很常见，可以在实验室中重现。期间 K99资金期间，我将使用D。黑腹-沃尔巴克氏体系统来表征和 确定细胞内和细胞间内共生体传递所需的基因/途径。 这将通过两个目标来实现：在目标1中，我将使用Wolbachia感染的果蝇细胞 线，探讨混合菌株的功能机制和进化结果， 感染.在目标2中，我将描述共生体和宿主连接蛋白Wolbachia用于 KHC依赖性微管运动。我将在R 00期间使用这项工作的结果 阶段，以探索细胞内和细胞间转移机制如何整合在整个苍蝇 通过生殖系垂直传播和宿主之间水平传播 个体因此，这项工作将提供机制的洞察力的传输策略 被世界各地的内共生体所使用。