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

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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.