# Modulation of epithelial memory by the microbiome

> **NIH NIH U19** · JACKSON LABORATORY · 2024 · $392,050

## Abstract

PROJECT SUMMARY PROJECT 2
The goal of Project 2 is to understand how age-related declines in lung immunity and antiviral response
relate to corresponding changes in the epigenome and respiratory microbiome. Older adults have
increased susceptibility to viral infection and adverse outcomes. Multiple factors contribute to this increased
susceptibility, including changes in innate immune memory and consequent changes in interactions with
commensal microbiota, which play an important role in the morphogenesis and maintenance of respiratory
immunity. Numerous epigenetic changes have been associated with aging-related disease. Our overarching
hypothesis is that age-related epigenetic changes in the lung epithelium are linked with an altered response to
the commensal microbiome, leading to chronic inflammation and altered tissue immunity to respond to viral
infection. In Project 1, we observed significant transcriptional differences in lung progenitors from older vs.
younger individuals. We seek here to determine, using bulk and single-cell genome-wide chromatin accessibility
assays of air-liquid interface (ALI) cultures developed from these older vs. younger lung progenitors, to what
degree epigenetic modifications drive these transcriptional changes and which are associated with altered viral
response (Aim 1). Then, we will investigate to what degree these aging-associated modifications affect
interactions with microbial stimuli (Aim 2), stimulating old/young ALI cultures with genetically diverse microbes,
examining phenotype and transcriptional response following colonization. Finally, we will investigate how the
collective changes in epithelial immunity resulting from age and differential microbial response affect interactions
with tissue-resident immune cells and collective influenza response (Aim 3), leveraging the Technology
Development Project's models integrating alveolar macrophages into ALI cultures. We anticipate that these
data will pinpoint microbial and epigenetic mechanisms contributing to lung immune aging, and how in turn these
changes affect viral response.

## Key facts

- **NIH application ID:** 10824108
- **Project number:** 2U19AI142733-06
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Julia Oh
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $392,050
- **Award type:** 2
- **Project period:** 2019-03-05 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824108

## Citation

> US National Institutes of Health, RePORTER application 10824108, Modulation of epithelial memory by the microbiome (2U19AI142733-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10824108. Licensed CC0.

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