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

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2024 · $230,247

## 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:** 11035927
- **Project number:** 3R35GM150803-02S1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Sampriti Mukherjee
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $230,247
- **Award type:** 3
- **Project period:** 2023-09-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11035927

## Citation

> US National Institutes of Health, RePORTER application 11035927, Probing the role of sensory cues in the regulation of bacterial biofilm development (3R35GM150803-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11035927. Licensed CC0.

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