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

昆虫和其他动物拥有肠道微生物群落(或“肠道微生物区系”)，这些微生物群落在它们的生物学中发挥着重要作用。然而，这些群落如何在肠道中聚集的潜在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)的研究人员合作的这个项目中，将使用先进的分子技术和实验方法来识别导致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，因为成年雌性蚊子可以传播寨卡病毒、登革热和其他会导致人类严重疾病的虫媒病毒。因此，这项工作的结果将大大加强我们对蚊子生物学的理解，并将其应用于人类和其他脊椎动物的疾病传播。研究结果还将扩大关于动物宿主如何控制细菌在肠道的定植的基础知识，反过来，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领导人。还将开发教育编程，供普通公众和初中、高中和本科生使用。这项美英合作项目得到了美国国家科学基金会和英国生物技术和生物科学研究委员会的支持。该项目寻求对肠道微生物组组装过程中宿主-微生物区系相互作用的机械性理解。到目前为止，协同进化主要是在高度稳定的长期关联的细菌伙伴中进行的，例如专性人类病原体。该项目的中心假设是，宿主-微生物区系的共同适应也可以在跨越非常短的时间尺度的重复相互作用中发生，并由宿主和细菌的遗传因素介导。三个具体目标将在埃及伊蚊身上解决这一假设，埃及伊蚊拥有简单的肠道细菌群落，可以进行实验操作。埃及伊蚊及其相关肠道细菌在基因上也是易驯服的。在目标1中，对蚊子的转录组测序和功能研究将确定控制微生物组获取和动态平衡的蚊子基因和途径。在目标2中，肠道定植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的研究将确定观察到的宿主-微生物区系相互作用在不同宿主蚊子物种中是否以及在多大程度上是保守的。结果将提高对肠道定植过程中宿主-微生物区系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峰研究项目和公民科学工具包，与教育和外联工作结合起来。结果将通过在同行评议期刊上发表和在科学会议上发表进一步分享。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.