MCA: Cockroach gut microbiome: Evaluating pressures from inflammation and bacteriophage

这项职业中期促进奖(MCA)将增加对宿主免疫系统和宿主肠道微生物集合(肠道微生物区系)之间关系的了解。众所周知，肠道微生物区系作为一个整体影响宿主健康，但对单个微生物所起的具体作用知之甚少。这项MCA奖将为希尔特博尔德·施瓦茨博士建立一个研究项目提供资源，以研究美国蟑螂的这个问题，美国蟑螂是一种在解决此类问题方面具有许多优势的有机体。蟑螂价格便宜，易于培养，既可以在没有微生物的情况下生长(无菌)，也可以只在特定的感兴趣的微生物(GnotoBiotic)中定居。这个系统将使我们能够更多地了解肠道微生物区系中特定成员的角色，不仅是在蟑螂身上，而且在其他动物中，也许也是在人类身上。该项目不仅将以关于宿主和微生物共生的新知识的形式为科学界提供有益的影响，而且还将提供与普通公众相关的见解。该奖项将为本科生和K-12学生提供科学教育和研究培训机会。最后，将免疫学专业知识应用于蟑螂(其免疫反应尚不完全了解)，将为希望研究其他特性不佳的生物的其他研究人员提供有用的见解。该项目的主要目标是更好地了解由噬菌体提供的对肠道细菌的选择压力，以及美国蟑螂美洲大蠊肠道微生物区系中的宿主免疫反应。虽然细菌是这个群落中最具特征的成分，但在调节细菌种群(噬菌体)方面发挥关键作用的其他生物却没有得到太多关注。此外，虽然细菌噬菌体的动态受到来自免疫系统的压力的调节，但宿主免疫系统的特定细胞与微生物区系之间的相互作用仍未完全确定。因此，对噬菌体-细菌和细菌-免疫动力学背后的生物过程的机械理解仍然是难以捉摸的。为了解决这些问题，我们提出了以下目标：1)利用常规和无菌美洲对虾确定肠道微生物区系如何影响血细胞的发育和功能；2)利用常规和灵知生物群确定肠道炎症如何影响噬菌体动态。这个项目的好处是多方面的。首先，我们将获得对昆虫血细胞的更多数量和功能的概述，以及它们的反应是如何由肠道微生物区系塑造的。其次，该奖项将通过两个新的互惠互利的合作来支持研究：一个是与一名专门研究蟑螂生理学的昆虫学家合作，另一项是与一名在无菌和灵媒蟑螂生成方面具有专业知识的合作伙伴。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。

This Mid-Career Advancement (MCA) award will increase understanding of the relationships between the host immune system and the collection of microbes that inhabit the host gut (the gut microbiota). It is well-known that the gut microbiota as a whole impacts host health, but little is known about the specific roles played by individual microbes. This MCA award will provide resources for Dr. Hiltbold Schwartz to build a research program to study this question in the American cockroach, an organism with many advantages for addressing such questions. Cockroaches are inexpensive, easily cultured, and can be grown either without microbes (germ-free) or may be colonized only with specific microbes of interest (gnotobiotic). This system will enable us to learn much about the roles of specific members of the gut microbiota not only in the cockroach, but in other animals and perhaps humans as well. This project will provide beneficial impacts not only for the scientific community in the form of new knowledge of the symbiosis between host and microbes but will also provide insights relevant to the general public. This award will provide scientific education and research training opportunities to under-represented students at the undergraduate level as well as K-12 students. Finally, the application of immunology expertise to the cockroach (where immune responses are incompletely understood), will provide insights useful to other investigators that wish to study immunity in other poorly characterized organisms.The primary objective of this project is to better understand the selective pressures on enteric bacteria provided by bacteriophage and by the host immune response in the gut microbiota of the American cockroach, Periplaneta americana. While bacteria are the most thoroughly characterized constituents of this community, other organisms that play key roles in regulating bacterial populations (bacteriophages) have received less attention. Further, while bacteria-phage dynamics are regulated by pressures from the immune system, the interactions between specific cells of the host immune system and the microbiota remain incompletely defined. Thus, a mechanistic understanding of the biological processes underlying phage-bacteria and bacteria-immune dynamics remains elusive. To address these questions, we propose the following objectives: 1) Determine how the gut microbiota impact the development and function of hemocytes utilizing conventional and germ-free P. americana and 2) Determine how bacteria-phage dynamics are impacted by gut inflammation utilizing conventional and gnotobiotic P. americana. The benefits of this project are numerous. First, we will gain a more quantitative and functional overview of insect hemocytes and how their responses are shaped by the gut microbiota. Secondly, this award will support research with two new, mutually-beneficial collaborations: one with an entomologist who specializes in cockroach physiology, and a second with a partner with expertise in generation of germ-free and gnotobiotic cockroaches.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.