RII Track-4:NSF: Determining the Functional Consequences of Co-adaptation Between Host and Gut Microbiota Across Closely Related Host Species

RII Track-4：NSF：确定密切相关宿主物种中宿主和肠道微生物群之间共同适应的功能后果

• 批准号: 2327485
• 负责人: Jeffrey Price
• 金额: $ 14.52万
• 依托单位: University of Nebraska-Lincoln
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2327485&HistoricalAwards=false
• 关键词: RII; Track; NSF; Determining; Functional

This Research Infrastructure Improvement Track-4 EPSCoR Research Fellows (RII Track-4) project will provide a fellowship to an Assistant Research Professor at the University of Nebraska-Lincoln. This work will be conducted in collaboration with researchers at the University of Washington. The bacteria that reside in the guts of animals affect a wide range of host traits. These include their digestion, metabolism, immunity, disease, and even behavior. However, there is relatively little current understanding of what a healthy set of gut bacteria looks like. In addition, how these sets are built in each host as they grow is also not well known. Over time, bacteria have adapted to their host animal species. Lab mouse-adapted bacteria grow more easily in the gut of lab mice than bacteria that come from other mouse species. So, there is a home-site advantage for these bacteria. It is not known if the opposite is true in other mouse species. This project will generate new tools to look at host-bacteria relationships, including brand new germ-free mice that are closely related to widely-used lab mice. Competition between bacteria adapted to each mouse line will show how these animals adapt to their bacteria. Particular attention will be paid to how the host immune system responds to each set of bacteria and if non-adapted bacteria result in poorer health for the mice. Understanding how bacteria and hosts adapt to each other is vital to improving health via treatment of the gut. This project will advance the University of Nebraska’s Gnotobiotic Mouse program's capabilities and enhance research capacity in Nebraska and the Midwest region.The gut microbiota is known to exert a tremendous influence over host metabolism, immune development, behavior, and many other traits. Hosts and microbiota have adapted to each other over many years, and species have distinct bacterial population profiles. However, a lack of appropriate model organisms, including germ-free Mus species other than the laboratory strain Mus musculus domesticus, has limited the resolution at which research about adaptations and interactions between hosts and their resident microbiota can be addressed. The goal of this project is to determine host-microbiota co-adaptations that affect the assembly of microbial populations in the gut and alter host development. This Research Infrastructure Improvement Track-4 EPSCoR Research Fellows (RII Track-4) project will provide a fellowship to an Assistant Research Professor at the University of Nebraska-Lincoln. This work will be conducted in collaboration with researchers at the University of Washington. This fellowship will train the PI in germ-free mouse rederivation techniques and generate a first-of-their-kind resource, germ-free Mus spicilegus (shrew mouse) and Mus pahari (steppe mouse), two mouse species closely related to laboratory mice. It will also produce critical data on adaptations between hosts and microbes that define how microbes assemble within gut communities and how host immune responses are affected by those bacteria. The new germ-free mouse lines will be generated by sterile cesarean murine births. The new mouse models will be reconstituted with conspecific (from the same mouse species) and heterospecific (from alternate mouse species) microbiota to evaluate whether adapted bacteria outcompete non-adapted species. Host immune responses educated by those bacteria with be analyzed to determine changes in host inflammation driven by responses to those bacteria. Understanding these basic microbe-host interactions and the mechanisms underlying them provides a strong rationale for eventual therapeutic alterations of the gut microbiome.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.

该研究基础设施改进 Track-4 EPSCoR 研究人员 (RII Track-4) 项目将为内布拉斯加大学林肯分校的助理研究教授提供奖学金。这项工作将与华盛顿大学的研究人员合作进行。动物肠道中的细菌会影响宿主的一系列特征，包括消化、新陈代谢、免疫、疾病，甚至行为。然而，目前对健康肠道细菌的了解相对较少。另外，这些集合是如何构建的随着时间的推移，细菌已经适应了它们的宿主动物物种，而在实验室小鼠的肠道中，它们的生长情况也并不为人所知。是这些细菌的家园优势，目前尚不清楚其他小鼠物种是否存在相反的情况，该项目将产生新的工具来研究宿主与细菌的关系，包括与宿主细菌密切相关的全新无菌小鼠。广泛使用的实验室小鼠之间的竞争适应每个小鼠品系。将展示这些动物如何适应其细菌。将特别关注宿主免疫系统如何对每组细菌做出反应，以及不适应的细菌是否会导致小鼠的健康状况较差。了解细菌和宿主如何相互适应。通过肠道治疗改善健康至关重要。该项目将提高内布拉斯加州大学的知生小鼠项目的能力，并增强内布拉斯加州和中西部地区的研究能力。众所周知，肠道微生物群对宿主代谢和免疫发育产生巨大影响。 ， 行为，宿主和微生物群多年来已经相互适应，并且物种具有独特的细菌种群特征，但是，由于缺乏适当的模式生物，包括除实验室菌株家鼠之外的无菌鼠物种。限制了有关宿主与其常驻微生物群之间的适​​应和相互作用的研究的分辨率，该项目的目标是确定影响肠道微生物群组装并改变宿主发育的宿主-微生物群的共同适应。研究基础设施改善Track-4 EPSCoR 研究人员 (RII Track-4) 项目将为内布拉斯加大学林肯分校的助理研究教授提供奖学金。这项工作将与华盛顿大学的研究人员合作进行。该奖学金将培训PI 无菌小鼠再衍生技术，并产生首创的资源，无菌小鼠 Mus spicilegus（鼩鼱小鼠）和 Mus pahari（草原小鼠），这两种与实验室小鼠密切相关的小鼠物种也将产生。批判的关于宿主和微生物之间的适应的数据，这些数据定义了微生物如何在肠道群落内组装以及宿主免疫反应如何受到这些细菌的影响，新的无菌小鼠品系将通过无菌剖腹产小鼠重建。同种（来自相同小鼠物种）和异种（来自不同小鼠物种）微生物群，以评估适应细菌是否胜过非适应物种，并分析这些细菌诱导的宿主免疫反应，以确定宿主炎症的变化。了解这些基本的微生物-宿主相互作用及其背后的机制为肠道微生物组的最终治疗改变提供了强有力的理由。该奖项反映了 NSF 的法定使命，并通过使用基金会的评估被认为值得支持。智力价值和更广泛的影响审查标准。