# Adding an environment and motility in a Whole Cell Model of Escherichia Coli

> **NIH NIH F32** · STANFORD UNIVERSITY · 2021 · $70,458

## Abstract

PROJECT SUMMARY
This proposal focuses on extending a large-scale “whole-cell” model (WCM) of Escherichia coli (wcEcoli) to
include a bacterial micro-environment and cell motility. wcEcoli is developed at the Covert lab at Stanford
University, and was recently released to an international community of scientists. The specific aims of this
application outline a plan to multi-scale the WCM, to introduce a simulated spatial environmentsthat can
include other cells -- this will lead to the very first whole-colony simulations. A cell’s environment significantly
impact its growth, division, and its overall phenotype throughout both a single cell cycle and evolutionary
timescales. By accounting for these influences, the extensions proposed here will open up a new domain for
whole-cell modeling that can examine cellular behavior in more natural environments.
 I worked with software engineers in the Covert lab to develop a preliminary multi-scale framework that
integrates whole-cell modeling with agent-based modeling techniques -- the result is a simulation that can
include multiple WCMs running in a spatial environment with molecular concentrations and physical forces.
With the training plan proposed here, I will develop and test this framework using the same standards that went
into the original WCM. This will lay a foundation for future extensions; the software will be built for scalable and
incremental modeling of new cell-environment interactions.
 I will begin integrating cell-environment interactions by focusing on E. coli chemotaxis. First, a gene
regulatory network will be implemented to control the expression of flagellar proteins; E. coli exhibit a
“just-in-time” mechanism for flagella expression, with proteins synthesized roughly in the order they are
needed. Monomers will be assembled into flagella complexes in the complexation module. A new flagella
module will model the motor activity of individual flagella, this will track the energy expenditure and will
generate motile forces that push the cell through its simulated environment. A sensory module will model the
activity of chemoreceptors, and their adaptation to signals by methylation. A signaling module will connect
sensory activity to the flagellar motor output with a protein network that controls the flagallas’ motor biases.
Finally, a transport module will model the trans-membrane uptake of nutrients from the local environment.
These transported nutrient fluxes will feed into the existing metabolism module and constrain its activity.
 The most exciting part of this project will be testing the wide-ranging consequences of E. coli’s
chemotaxis behavior on cellular physiology. To survive in the wild, E. coli needs to process noisy information
and make quick survival decisions. Information processing and motility require the necessary molecules and
energy, and this cost needs to be offset by reliably securing key resources. Systematic analysis of wcEcoli will
determine many of the trade-off...

## Key facts

- **NIH application ID:** 10396393
- **Project number:** 3F32GM137464-01S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Eran Agmon
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,458
- **Award type:** 3
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396393

## Citation

> US National Institutes of Health, RePORTER application 10396393, Adding an environment and motility in a Whole Cell Model of Escherichia Coli (3F32GM137464-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10396393. Licensed CC0.

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