# Cell-cell interactions and the development of bacterial communities

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2024 · $313,760

## Abstract

PROJECT ABSTRACT
In nature, bacteria primarily exist in biofilms – dense surface-attached communities of cells embedded in an
extracellular matrix. Many advantages accrue to the bacteria living in biofilms, including adhesion to surfaces,
resistance to antibiotics and predation, and collective processing of nutrient sources. From a human perspective,
biofilms can be beneficial, e.g. in the context of the microbiome and bioremediation. However, biofilms can also
be problematic, e.g. biofilms cause major problems in medicine as they lead to chronic infections, and in industry
biofilms foul surfaces and clog filtration devices. How biofilms assemble and disassemble depends on the
particular bacterial species, but there exist broadly general principles. To pursue investigations of overarching
principles, here we ask the fundamental question: how are biofilms able to achieve coherent population-level
outcomes, such as synchronous disassembly and dispersal, despite large stochastic variation (“noise”) in single-
cell gene expression? In a breakthrough enabled by light-sheet microscopy, we have recently tracked the
individual cells in living, growing biofilms of the model pathogen Vibrio cholerae, from a single founder cell up to
10,000 cells. Therefore, we are now in a position to couple light-sheet imaging with our existing fluorescent
reporters of single-cell gene expression to measure noise at the individual-cell level within living V. cholerae
biofilms. These new data will empower us to address our fundamental question, with a focus on these key facets:
(1) How much information do individual cells possess about their spatiotemporal location within a biofilm? (2)
How do biofilm cells integrate multiple time-dependent sensory inputs to decide whether and when to disperse,
and is this decision made collectively or at the single-cell level? Answering these questions will require a close,
iterative merger of experiments with biophysical modeling. Particular modeling innovations will be information-
theoretic studies of single biofilms cells transitioning from low to high cell density, pathway-based analysis of the
integration of quorum-sensing and nutrient-derived signals, agent-based mechanical simulation of dispersal from
a biofilm, and development of a continuum model for the entire dispersal process. Our studies of the emergence
of precise collective behaviors from noisy single cells in this tractable model system will provide a paradigm for
similar analyses across bacterial species, and for coherent multicellular processes more generally.

## Key facts

- **NIH application ID:** 10900582
- **Project number:** 5R01GM082938-15
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** NED S WINGREEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $313,760
- **Award type:** 5
- **Project period:** 2008-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900582

## Citation

> US National Institutes of Health, RePORTER application 10900582, Cell-cell interactions and the development of bacterial communities (5R01GM082938-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10900582. Licensed CC0.

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