Nancy A. Moran

Research Projects in the moran lab

The molecular bases of interbacterial and bacterial-host interactions in microbial communities

(PI is Nancy Moran)

Bacterial communities associated with animals have substantial effects, positive and negative, on hosts and are critical factors in health status, including that of humans. The processes shaping these outcomes are complex, as they result from interdependent interactions among microbes and between microbes and hosts. Simple, tractable experimental models are essential to better understand how microbiomes are shaped and how they affect hosts. Insects offer such models and are used here to address (1) how interbacterial competitive interactions affect microbiome composition and the host, (2) how hosts choose beneficial over harmful bacterial colonizers, and (3) how intracellular symbionts escape destruction by host cells. Understanding forces shaping microbial communities is key to efforts to control microbiomes to improve health. The bee gut microbiome is dominated by fewer than ten bacterial species, all of which can now be grown in lab culture, manipulated with genetic tools, and visualized within the host. Although far simpler, this community has many parallels with the human gut microbiome, including restriction of members to the host gut, transmission through social contact, interactions with host immune systems, and presence in the distal gut where members help to digest dietary polysaccharides. This research program takes advantage of our past decade of progress in developing genetic and experimental tools for bee gut bacteria, enabling detailed interrogation of processes that govern microbiome composition and effects on hosts. In both humans and bees, a stable, healthy gut community bestows colonization resistance: the exclusion of foreign, potentially harmful, microorganisms. This project will identify sources of colonization resistance, which can include modulation of host immune responses and/or interbacterial antagonism via secreted toxins. Experiments will examine whether resident community members are more tolerant to immune effectors or antagonism mechanisms and how localization within the gut affects tolerance. These processes and how they affect host health will be investigated using newly developed genetic tools that allow targeted mutations and markers for visualization within bee guts. We also will develop genetic tools for newly described, host-specialized gut bacteria of Drosophila, with the goal of using this well- established genetic model for deeper understanding of host pathways affecting symbiont colonization. Intracellular symbioses offer the opportunity to examine intimate one-on-one interactions between host and symbiont, and to address how host cells respond to bacteria that enter the cytoplasm. This research will address how beneficial endosymbionts evade destructive lysosomal responses to intracellular pathogens. We will determine how the obligate symbionts of aphids deploy mechanisms derived from pathogenic ancestors to shut down the host response, thereby enabling their long-term persistence within the host cell. The broad goals of the research program are to identify which kinds of bacterial interactions and host responses are important in shaping symbiont communities and how these result in benefit or harm to hosts.

Selected publications

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