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

这个中期职业发展（MCA）奖将增加对宿主免疫系统与栖息在宿主肠道（肠道微生物群）中的微生物集合之间关系的理解。 众所周知，肠道微生物群作为一个整体会影响宿主的健康，但对单个微生物所起的具体作用知之甚少。这个MCA奖将为Hiltbold Schwartz博士提供资源，以建立一个研究计划来研究美洲蟑螂中的这个问题，美洲蟑螂是一种在解决这些问题方面具有许多优势的生物体。 蟑螂价格便宜，易于培养，可以在没有微生物（无菌）的情况下生长，也可以只与特定的微生物（gnotobiotic）一起生长。 这个系统将使我们能够了解肠道微生物群特定成员的作用，不仅在蟑螂中，而且在其他动物，也许还有人类中。 该项目不仅将以宿主和微生物之间共生关系的新知识的形式为科学界提供有益的影响，而且还将提供与公众相关的见解。该奖项将提供科学教育和研究培训机会，在本科层次的代表性不足的学生以及K-12学生。最后，将免疫学专业知识应用于蟑螂（在免疫反应不完全理解的情况下），将为希望研究其他特征不佳的生物体中的免疫的其他研究者提供有用的见解。本项目的主要目标是更好地理解噬菌体和美国蟑螂肠道微生物群中宿主免疫反应对肠道细菌提供的选择性压力，美洲大蠊虽然细菌是该群落中最彻底的特征成分，但在调节细菌种群（噬菌体）中发挥关键作用的其他生物体却很少受到关注。此外，虽然细菌-噬菌体动力学受来自免疫系统的压力调节，但宿主免疫系统的特定细胞与微生物群之间的相互作用仍然不完全确定。因此，对噬菌体-细菌和细菌-免疫动力学的生物学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）确定肠道微生物群如何影响利用常规和无菌美洲假单胞菌的血细胞的发育和功能，以及2）确定细菌-噬菌体动力学如何受到利用常规和无菌美洲假单胞菌的肠道炎症的影响。 这个项目的好处是多方面的。首先，我们将获得昆虫血细胞的更定量和功能概述，以及肠道微生物群如何塑造它们的反应。 其次，该奖项将通过两项新的互利合作来支持研究：一项是与专门研究蟑螂生理学的昆虫学家合作，另一项是与具有无菌和非细菌蟑螂产生专业知识的合作伙伴合作。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的智力价值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.