# A model-driven investigation into the role of operon structure and sub-generational expression in Escherichia coli

> **NIH NIH F32** · STANFORD UNIVERSITY · 2020 · $53,869

## Abstract

PROJECT SUMMARY
A recent finding from the Covert lab is that the majority of genes in the ​E. coli ​genome are predicted to be
expressed less than once per generation, termed sub-generational expression. Sub-generational genes
include many essential genes, as well as genes that are crucial for responding to different environmental
challenges. Another feature of bacterial gene regulation is the operon, which is a genomic unit composed of
several genes expressed under the control of a single promoter. This structural feature of the bacterial genome
means that stochastic activation of one promoter can result in the simultaneous expression of multiple genes.
Operons often contain functionally-related genes, and it has been hypothesized that operons exist to couple
transcription and translation (though this has been long-debated in the field). In the context of sub-generational
expression, this role of operon structure seems critical. For example, if two components of a heterodimer are
both expressed sub-generationally from separate promoters it is unlikely that these two proteins will be present
at the same time. However, even with a low probability of promoter activation, if the production of these two
monomers is coupled through operon structure these transcriptional bursts will result in protein coexpression
and functional heterodimers. Thus, the combination of sub-generational expression and operon structure could
produce subpopulations of cells which simultaneously express all proteins in a complex or pathway, enabling
these cells to respond to an environmental perturbation. Across a population of cells, these stochastic
expression events create gene expression heterogeneity, which could protect the population against a large
variety of potential challenges. Without operon structure, it is unlikely that these subpopulations of cells would
exist. ​In this proposal, I will use both experimental and computational methods to determine the role of operon
structure in the context of sub-generational expression, and evaluate if these two features of bacterial gene
expression lead to increased fitness in response to environmental shifts​. Through this fellowship, I will 1)
develop a novel understanding of the role of operon structure in ​E. coli​, 2) continue to develop skills to
integrate computational and experimental approaches, and 3) develop my potential as an independent
investigator. These goals will be made possible by the detailed research plan, my exceptionally qualified
mentor, and the incredible facilities and training resources available at Stanford University.

## Key facts

- **NIH application ID:** 9988799
- **Project number:** 1F32GM137528-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Taryn Gillies
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $53,869
- **Award type:** 1
- **Project period:** 2020-04-01 → 2021-01-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988799

## Citation

> US National Institutes of Health, RePORTER application 9988799, A model-driven investigation into the role of operon structure and sub-generational expression in Escherichia coli (1F32GM137528-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9988799. Licensed CC0.

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