# Elucidating mechanisms of acetylcholine signaling in bacterial biofilms

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2022 · $42,601

## Abstract

Project Summary
While microbes are single-celled organisms, they naturally form densely packed communities known as biofilms.
Biofilms pose a major public health challenge as they often cause difficult-to-treat infections that exhibit
properties such as antimicrobial resistance and persistence even with long courses of antibiotics. Since
microbiology research has often been conducted using domesticated strains under controlled laboratory
conditions where biofilms do not form, there is a need for understanding emergent behavior that only exists in
biofilms. Integrating bacterial gene regulation and metabolism with biofilm morphology and behavior requires a
model system with sufficiently mapped genetic and metabolic pathways, established genetic tractability, and
known biofilm growth conditions. For these reasons, Bacillus subtilis is considered a model organism for biofilm
studies. Bacillus subtilis biofilms are composed of a network of resident cells and tightly regulated extracellular
matrix. Initial biofilm formation and matrix expression is controlled by the expression of master regulators that
respond to traditional quorum-sensing molecules. However, newly appreciated ion-based signaling in Bacillus
subtilis is critical for community level fitness by coordinating nutrient sharing within a biofilm. This discovery
highlights signaling pathways that are critical for the formation and overall fitness of biofilms yet remain
undiscovered. To help close this gap in knowledge, we will focus on discovering the synthesis genes for
acetylcholine and acetylcholine-based cell-to-cell signaling phenotypes. Our leading hypothesis is acetylcholine
acts as a signaling molecule in cell-to-cell communications within biofilms. Aim 1 will identify acetylcholine biofilm
signaling phenotypes using microscopy and Aim 2 will identify the genes responsible for acetylcholine synthesis.
The overarching goal of this project is to provide the first description of genetic, metabolic, and physiological
mechanisms for acetylcholine in all bacterial species. Additionally, the function of and synthesis gene(s)
responsible for acetylcholine production will provide the scientific community with the foundational knowledge to
explore bacterial homologs in other species and how signaling within bacteria may also impact complex systems
like the human gut-brain-axis in development and disease.

## Key facts

- **NIH application ID:** 10538066
- **Project number:** 1F31GM143907-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Stephen Lander
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,601
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10538066

## Citation

> US National Institutes of Health, RePORTER application 10538066, Elucidating mechanisms of acetylcholine signaling in bacterial biofilms (1F31GM143907-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10538066. Licensed CC0.

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