Regulation of tissue barriers during host microbe interactions

The National Institute of General Medical Sciences awarded Yale University $462,000 in project grant funding on August 1, 2026, to study the regulation of tissue barriers during host-microbe interactions under the Biomedical Research and Research Training program (CFDA 93.859).

The research combines single-cell and spatial genomics, biosensors, and genetic approaches across plant species to map the transcriptional and hormonal networks governing microbial colonization, immune activation, and barrier function. The work focuses on how local immune responses organized at the level of individual cell types integrate into systemic protection, particularly in plant roots where immune activation is highly spatially organized and direct interactions with dense microbial communities occur.

The period of performance runs through June 30, 2031, with work performed at Yale University's New Haven, Connecticut campus.

Abstract

All multicellular organisms must strike a balance between supporting beneficial microbes and defending against harmful pathogens. A key part of this balance is the compartmentalization of host tissues through barrier structures such as epithelia and cell-cell junctions, which limit microbial access and preserve host integrity. Beyond physical barriers, immune systems also fine- tune responses by distinguishing pathogens from symbionts and tailoring responses accordingly. As tissues became more specialized through evolution, immune responses had to become context-dependent and cell type-specific. Yet the mechanisms by which these localized programs scale to systemic protection remain largely unknown. Plants have served as preeminent model systems for understanding the mechanisms of innate immunity and its regulation. They provide a powerful system to study these complexities, particularly in roots where immune activation is highly spatially organized. Distinct cell types deploy unique transcriptional programs, governed by networks integrating cell identity. Roots interact directly with dense microbial communities, show striking cell type-specific patterns of immune activation. Intriguingly, certain root-associated beneficial microbes trigger a whole-plant systemic enhancement of defense, mediated by interconnected hormonal signaling and transcriptional networks. However, the mechanisms that convert local immune cues into systemic signals, and which cells initiate these processes, are not yet understood. This research program seeks to uncover how local immune responses are organized at the level of individual cell types and how they are integrated into systemic protection. We will combine single-cell and spatial genomics, biosensors, and genetic approaches across plant species to map the transcriptional and hormonal networks that govern microbial colonization, immune activation, and barrier integrity. By identifying how cell identity shapes immunity and how local interactions generate long-distance defense signals, we will build a mechanistic framework for understanding how hosts maintain beneficial microbial partnerships while resisting pathogens. Our goal is to establish a mechanistic framework explaining how multicellular hosts maintain beneficial symbioses while preventing pathogen invasion. This aligns with the mission of nigms by advancing foundational knowledge of genetic and regulatory networks governing organismal function. Insights gained will offer broad biological principles applicable to both plant and animal host-microbe interactions, informing strategies for improving health and resilience.