Tsetse-microbiota negotiations mediated by microRNAs

microRNA 介导的采采蝇-微生物群协商

• 批准号: 10282112
• 负责人: Rita V M Rio
• 金额: $ 22.8万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10282112
• 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.

项目摘要 采采蝇（双翅目：舌蝇科）是非洲锥虫（Trypanosoma 布氏杆菌属）这是致命的人类非洲锥虫病（HAT）的病原体， 非洲锥虫（AAT）在野生和驯养动物。分类简单的采采蝇 肠道微生物群由专性细菌互利共生菌Wigglesophagia占主导地位。单一文化 细胞内的Wigglesophoria被发现在一个专门的器官，称为细菌组，位于 前中肠采采蝇生物学中的几个关键角色，从必需营养素 提供免疫引发，已被表征为Wigglesophoria。重要的是 消除（或功能性破坏）采采蝇-Wigglesophagia协会导致滞后于采采蝇 发展和生殖产出大幅度减少。我们的长期目标是扩大我们的 了解协调采采-威格尔斯氏菌活动的分子机制。这里 舌蝇产生的microRNAs（miRNAs）对促进代谢和发育的作用 Wigglesworthia-tsetse共生的整合将被检查。我们的研究设计涉及 鉴定在细菌组内差异表达的miRNA（相对于非共生体 在采采蝇性别特异性发育和妊娠期间使用基于深度测序的 接近。此外，这些miRNAs的基因靶点将使用 计算基因组学破坏miRNA-275的作用，在细胞内显著上调， 妊娠采采蝇的细菌组，对采采蝇生活史特征，细菌组完整性和 将表征摆动密度。这个项目旨在解开基本的分子 协调宿主微生物生物学的机制。关键的Wigglesworthia介导的破坏 采采蝇体内的代谢过程为生物防治提供了新的目标。