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BBSRC-NSF/BIO: Bacterial and host genetic factors contributing to microbiome acquisition and homeostatis in mosquitoes

BBSRC-NSF/BIO：有助于蚊子微生物组获得和稳态的细菌和宿主遗传因素

基本信息

批准号：
2019368
负责人：
Kerri Coon
金额：
$ 103.5万
依托单位：
University of Wisconsin-Madison
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2019368&HistoricalAwards=false
关键词：
BBSRC NSF BIO Bacterial host

项目摘要

Insects and other animals harbor intestinal microbial communities (or ‘gut microbiota’) that play important roles in their biology. However, the processes underlying how these communities assemble in the gut remain largely unexplored. In this collaborative project between researchers at the University of Wisconsin-Madison (US) and the Liverpool School of Tropical Medicine (UK), advanced molecular techniques and experimental approaches will be used to identify the genetic factors contributing to gut microbiota assembly in the mosquito Aedes aegypti, an insect of significant interest because adult females can transmit Zika, dengue, and other arboviruses that cause severe disease in humans. Results from this work will therefore significantly enhance our understanding of mosquito biology with applied relevance to disease transmission in humans and other vertebrates. Results will also expand fundamental knowledge of how animal hosts control gut colonization by bacteria and, conversely, how bacteria adapt to the gut to form stable associations with their animal hosts. Broader impacts of this project to society include the scientific training of postdoctoral researchers and students at the graduate and undergraduate levels to become the next generation of STEM leaders. Educational programming will also be developed for use by the general public and students at the middle, high school, and undergraduate levels. This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.This project seeks a mechanistic understanding of host-microbiota interactions during gut microbiome assembly. To date, co-evolution has been investigated largely in bacterial partners of highly stable, long-term associations such as obligate human pathogens. The central hypothesis of this project is that host-microbiota co-adaptation can also occur over repeated interactions spanning very short time scales and is mediated by genetic factors of both hosts and bacteria. Three specific aims will address this hypothesis in the mosquito Aedes aegypti, which harbors simple gut bacterial communities that can be experimentally manipulated. Both A. aegypti and its associated gut bacteria are also genetically tractable. In Aim 1, transcriptome sequencing and functional studies in mosquitoes colonized by defined microbiomes of varying genetic complexity will identify mosquito genes and pathways that control microbiome acquisition and homeostasis. In Aim 2, experimental evolution and transcriptome sequencing of bacteria during gut colonization will identify how bacteria adapt to the mosquito gut environment and establish mixed communities. Finally, studies in Aim 3 will establish whether and to what extent observed host-microbiota interactions are conserved across different host mosquito species. Results will improve understanding of host-microbiota gene interactions during gut colonization and provide valuable long-term genomic and transcriptomic resources to the broader scientific community. This research will also be integrated with education and outreach through the training of postdoctoral and graduate researchers and the development of an undergraduate capstone research project and citizen science toolkit. Results will further be shared through publication in peer-reviewed journals and presentation at scientific meetings.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

昆虫和其他动物的肠道微生物群落（或“肠道微生物群”）在其生物学中起着重要作用。然而，这些社区如何在肠道中组装的过程在很大程度上仍未被探索。在威斯康星大学麦迪逊分校（美国）和利物浦热带医学院（英国）的研究人员之间的这个合作项目中，先进的分子技术和实验方法将用于确定有助于埃及伊蚊肠道微生物群组装的遗传因素，埃及伊蚊是一种重要的昆虫，因为成年雌性可以传播寨卡病毒，登革热，和其他能引起人类严重疾病的虫媒病毒。因此，这项工作的结果将大大提高我们对蚊子生物学的理解，并与人类和其他脊椎动物的疾病传播有关。结果还将扩大动物宿主如何控制细菌肠道定植的基础知识，相反，细菌如何适应肠道与动物宿主形成稳定的联系。该项目对社会的更广泛影响包括对博士后研究人员和研究生和本科生进行科学培训，使其成为下一代STEM领导者。还将开发教育程序，供公众和初中、高中和大学生使用。这个美国/英国合作项目由美国国家科学基金会和英国生物技术和生物科学研究理事会支持。该项目旨在了解肠道微生物组组装过程中宿主-微生物群相互作用的机制。迄今为止，协同进化主要是在高度稳定的长期关联的细菌伴侣中进行研究，例如专性人类病原体。该项目的核心假设是宿主-微生物群共适应也可以在非常短的时间尺度上重复相互作用，并由宿主和细菌的遗传因子介导。三个具体的目标将解决这一假设在蚊子埃及伊蚊，其中窝藏简单的肠道细菌群落，可以通过实验操作。A.埃及伊蚊及其相关的肠道细菌在遗传上也是易处理的。在目标1中，在蚊子中进行转录组测序和功能研究，这些蚊子被具有不同遗传复杂性的确定的微生物组定殖，将确定控制微生物组获得和稳态的蚊子基因和途径。在目标2中，肠道定殖期间细菌的实验进化和转录组测序将确定细菌如何适应蚊子肠道环境并建立混合群落。最后，目标3中的研究将确定所观察到的宿主-微生物群相互作用是否以及在多大程度上在不同的宿主蚊子物种中是保守的。研究结果将提高对肠道定植过程中宿主-微生物群基因相互作用的理解，并为更广泛的科学界提供有价值的长期基因组和转录组资源。这项研究还将通过培训博士后和研究生研究人员以及开发本科生顶点研究项目和公民科学工具包，与教育和外联相结合。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。