# From cell-to-cell heterogeneity to collective behaviors in bacterial biofilms

> **NIH NIH R35** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $409,131

## Abstract

PROJECT SUMMARY
Bacterial biofilms are communities of bacteria stuck together by a self-produced polymer matrix.
They exist in nearly every environment on earth and are the cause of most hospital-borne
infections. These adherent communities are highly tolerant of antibiotics and their extreme
resilience cannot merely be attributed to the inability of drug molecules to penetrate the biofilm
matrix. It has become clear that emergent, multicellular behaviors in biofilms impart unique
survival strategies. In recent years, we have learned detailed mechanisms of gene regulation
and phenotypic heterogeneity of single bacterial cells, but we have neither explored these
cellular phenomena in the context of crowded, multicellular biofilms, nor do we understand how
multicellular behaviors emerge from these single-cell properties. The goal of my lab for the next
five years will be to understand how single-cell properties and physics of the local environment
give rise to beneficial emergent behaviors in biofilms. With this MIRA award, my group will
explore these questions by focusing on two collective phenomena: 1) electrical cell-to-cell
communication and 2) emergence of patterns of motile and matrix-producing cells during biofilm
development. We will approach these problems using spatial gene expression measurements,
single-cell-level time-lapse imaging of biofilms, and novel transistor devices for electrical
perturbation of biofilms. To probe the emergence of group behaviors from single-cell properties,
we will use the experimental biofilm model species Bacillus subtilis to perturb known cell-to-cell
communication mechanisms and gene regulatory circuits. Our data will inform quantitative
models of multicellular phenomena, which will give us a system-level understanding of
multicellular behaviors in microbes, as well as suggesting new hypotheses and targets for
disrupting the emergent behaviors that allow biofilms to elude treatment.

## Key facts

- **NIH application ID:** 10273402
- **Project number:** 1R35GM142584-01
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Joseph W Larkin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $409,131
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10273402

## Citation

> US National Institutes of Health, RePORTER application 10273402, From cell-to-cell heterogeneity to collective behaviors in bacterial biofilms (1R35GM142584-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10273402. Licensed CC0.

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