# Probing the role of sensory cues in the regulation of bacterial biofilm development

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2024 · $401,296

## Abstract

PROJECT SUMMARY
Bacteria have a remarkable ability to sense diverse stimuli and make regulatory decisions to elicit an appropriate
response. The objective of our research program is to understand the molecular underpinnings of this cellular
decision-making process during the development of three dimensional (3D) structured communities called
biofilms. Biofilms represent a predominant bacterial lifestyle and are crucial for antimicrobial tolerance, virulence,
and environmental persistence in diverse pathogens including multi-drug resistant Pseudomonas aeruginosa.
P. aeruginosa serves as an ideal clinically relevant model system for our basic research in biofilms because it
adapts to and forms biofilms in a wide variety of environments, and the biofilm matrix components in this
organism are well characterized. The overarching goal of the proposed research is to define how bacteria decode
and integrate sensory cues – physical, chemical and biological – over the course of the biofilm development
cycle. My work has shown that light (physical cue) detected via bacteriophytochrome BphP photoreceptor
mediated photo sensing and population density (biological cue) detected via RhlR mediated quorum sensing
represses biofilms. Furthermore, we have discovered that nutrient availability (chemical cue) converges with
quorum sensing (biological cue) to control biofilm matrix components and architecture. Over the next five years,
we will build on our recent discoveries and use a multidisciplinary approach combining bacterial genetics,
molecular biology, biochemistry, fluorescence microscopy, mathematical modeling, structural biology and
genome-scale studies to define sensory signaling in the context of a growing biofilm. First, we will investigate
how light is perceived locally and globally in heterogenous biofilms and characterize the BphP photo-sensing
signaling system to understand the regulation of photo sensing in P. aeruginosa (Project 1). Second, we will
dissect the CbrA-Crc nutrient-sensing pathway to learn how nutrient availability controls biofilm development
(Project 2). Third, we will delineate the different ways by which RhlR mediated quorum sensing represses biofilm
formation (Project 3). Finally, we will define how information from two or more distinct sensory signaling pathways
are combined in the control of collective behaviors (Project 4). Our research will establish a broadly relevant
framework for understanding how information encoded in diverse sensory inputs is extracted and integrated to
drive collective behaviors – knowledge that is crucial for designing successful synthetic strategies to enhance or
to inhibit biofilms and for developing novel therapeutic interventions.

## Key facts

- **NIH application ID:** 10910003
- **Project number:** 5R35GM150803-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Sampriti Mukherjee
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $401,296
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910003

## Citation

> US National Institutes of Health, RePORTER application 10910003, Probing the role of sensory cues in the regulation of bacterial biofilm development (5R35GM150803-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10910003. Licensed CC0.

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