Tsetse-microbiota negotiations mediated by microRNAs

microRNA 介导的采采蝇-微生物群协商

• 批准号: 10452605
• 负责人: Rita V M Rio
• 金额: $ 19万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-16 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452605
• 关键词: African; African Trypanosomiasis; Age; Animals; Anterior; Biocontrols; Biological; Biology; Blood; Coupled; Data; Development; Diet; Digestion; Diptera; Distant; Domestic Animals; Experimental Designs; Female; Gastrointestinal tract structure; Gene Targeting; Genes; Genomics; Glossinidae; Homeostasis; Human; Immunologics; Indigenous; Insecta; Invertebrates; Knowledge; Maintenance; Mediating; Mediation; Messenger RNA; Metabolic; Metabolism; MicroRNAs; Midgut; Molecular; Nutrient; Organ; Output; Pathogenicity; Pathway interactions; Periodicity; Pest Control; Physiology; Population; Pregnancy; Public Health; RNA library; Reproduction; Research Design; Role; Signal Transduction; Small RNA; Symbiosis; Taxonomy; Testing; Trypanosoma; Trypanosoma brucei brucei; Tsetse Flies; Wigglesworthia; Wild Animals; Work; aged; bacteriome; base; comparative; cost; deep sequencing; density; dietary; differential expression; fitness; fly; gut microbiota; host microbiota; in vivo; life history; male; member; microbial; microbiota; next generation sequencing; novel; pregnant; reproductive; sex; stomach cardia; symbiont; trait; transcriptome sequencing; transmission process; vector; vector control

Project summary Tsetse flies (Diptera: Glossinidae) are the cyclical vectors of African trypanosomes (Trypanosoma brucei spp.) which are the causative agents of fatal Human African Trypanosomiasis (HAT), and Animal African Trypanosomiasis (AAT) in wild and domesticated animals. The taxonomically simple tsetse enteric microbiota is dominated by an obligate bacterial mutualist, Wigglesworthia. A monoculture of intracellular Wigglesworthia is found within a specialized organ, known as the bacteriome, located at the anterior midgut. Several critical roles towards tsetse biology, spanning from essential nutrient provisioning to immunological priming, have been characterized for Wigglesworthia. Importantly, the elimination (or functional disruption) of the tsetse- Wigglesworthia association results in lags to tsetse development and sizeable reductions in reproductive output. Our long-term objective is to expand our understanding of the molecular mechanisms that coordinate tsetse-Wigglesworthia activity. Here, the role of tsetse-generated microRNAs (miRNAs) towards facilitating the metabolic and developmental integration of Wigglesworthia-tsetse symbiosis will be examined. Our research design involves the identification of miRNAs that are differentially expressed within bacteriomes (relative to non-symbiont harboring organs) during tsetse sex-specific development and pregnancy using deep sequencing-based approaches. Additionally, the gene targets of these miRNAs will be initially identified using computational genomics. The effect(s) of disrupting miRNA-275, significantly upregulated within the bacteriomes of pregnant tsetse, towards tsetse fly life history traits, bacteriome integrity and Wigglesworthia density will be characterized. This project aims to unravel fundamental molecular mechanisms that coordinate host-microbiota biology. The disruption of pivotal Wigglesworthia-mediated metabolic processes within tsetse offers novel targets for biocontrol.

项目概要 采采蝇（双翅目：舌蝇科）是非洲锥虫（Trypanosoma）的循环载体 brucei spp.），这是致命的人类非洲锥虫病（HAT）的病原体，以及动物 野生和家养动物中的非洲锥虫病 (AAT)。分类学简单的采采蝇 肠道微生物群以专性细菌共生体 Wigglesworthia 为主。单一栽培 细胞内 Wigglesworthia 存在于一个称为细菌组的特殊器官内，该器官位于 前中肠。对采采蝇生物学的几个关键作用，包括必需营养素 Wigglesworthia 已被表征为提供免疫启动。重要的是， 采采蝇- Wigglesworthia 关联的消除（或功能破坏）导致采采蝇滞后 发育和生殖产出的大幅减少。我们的长期目标是扩大我们的 了解协调采采蝇-Wigglesworthia 活性的分子机制。在这里， 采采蝇产生的 microRNA (miRNA) 在促进代谢和发育方面的作用 将检查 Wigglesworthia-采采蝇共生的整合。我们的研究设计涉及 鉴定细菌组内差异表达的 miRNA（相对于非共生体） 使用基于深度测序的采采蝇性别特异性发育和妊娠期间的（包含器官） 接近。此外，这些 miRNA 的基因靶点将通过以下方法初步确定： 计算基因组学。破坏 miRNA-275 的效果，在 怀孕采采蝇的细菌组，针对采采蝇的生活史特征、细菌组完整性和 将表征 Wigglesworthia 密度。该项目旨在解开基本分子 协调宿主微生物群生物学的机制。 Wigglesworthia 介导的关键破坏 采采蝇体内的代谢过程为生物防治提供了新的目标。