# Vibrio fischeri as a Model for Bacterial Colonization

> **NIH NIH R37** · CARNEGIE INSTITUTION OF WASHINGTON, D.C. · 2024 · $695,395

## Abstract

The long-term goals of the proposed research program are to provide insight into the complex dialogue that
occurs each generation between humans and their microbiota during the critical period following birth.
Recent research has indicated a strong correlation between outcomes of these early events and life-long
health. However, the inaccessibility of colonized tissues and high diversity of the microbiota renders an in-
depth study of early colonization of human tissues extremely challenging. When faced with such complex
phenomena, biologists often turn to simpler model systems to provide insights into evolutionarily conserved
features and reveal basic principles. To decipher the cellular and molecular mechanisms underlying the
initiation of bacterial associations with apical surfaces of mucosal epithelia, the proposed program exploits
the binary symbiosis between the bacterium Vibrio fischeri and its squid host, Euprymna scolopes. This
relatively simple association has been studied for over two decades as a model for the chronic colonization
of mucosa by Gram-negative bacteria. As in humans, the squid-vibrio association begins anew each
generation, requiring a ‘winnowing’ of other environmental bacteria that results in persistent association
restricted to the coevolved partners. In this system, the process of symbiosis initiation occurs across ~100
microns over minutes to hours. It can be directly imaged in its entirety using confocal microscopy, which
offers the rare opportunity to define, with high temporal and spatial resolution, the reciprocal molecular and
biochemical dialogue that results in the establishment of a specific, life-long beneficial symbiosis. This
project brings together two collaborators, each with expertise in the biology of one of the symbiotic
partners, and introduces new technology to the study of host-microbe interactions, including: HCR-FISH,
which enables visualization of rare transcripts in host and symbiont cells; NanoString, a new technology for
simultaneous analysis of dozens to hundreds of targeted transcripts; and high-efficiency RNAseq, which
produces robust transcriptional libraries from as little as 10 ng total RNA (~105 bacteria). An understanding
of the human microbiome is in its infancy, and this frontier field is currently at the stage of building
paradigms. Within this context, as the squid-vibrio system has in the past, the results of the current study
will shed light upon fundamental principles governing the onset of both beneficial and pathogenic
associations.
RELEVANCE (See instructions): During the colonization of humans and other animals, by either the normal
microbiota or microbial pathogens, the first few hours are critical. The resulting interplay determines
whether a healthy association will be fostered, a dysfunctional community will develop, or a frank
pathogenesis will ensue. We will use innovative imaging, microbial genetics, and genomics/transcriptomics
approaches to discover the molecular ...

## Key facts

- **NIH application ID:** 10802280
- **Project number:** 5R37AI050661-22
- **Recipient organization:** CARNEGIE INSTITUTION OF WASHINGTON, D.C.
- **Principal Investigator:** MARGARET J MC FALL-NGAI
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $695,395
- **Award type:** 5
- **Project period:** 2001-12-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802280

## Citation

> US National Institutes of Health, RePORTER application 10802280, Vibrio fischeri as a Model for Bacterial Colonization (5R37AI050661-22). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10802280. Licensed CC0.

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