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Bacterial variability in the mammalian gut captured by a single-cell synthetic oscillator

Author

Listed:
  • David T. Riglar

    (Harvard Medical School
    Harvard University
    Imperial College London)

  • David L. Richmond

    (Harvard Medical School)

  • Laurent Potvin-Trottier

    (Harvard Medical School
    Concordia University)

  • Andrew A. Verdegaal

    (Harvard Medical School)

  • Alexander D. Naydich

    (Harvard Medical School
    Harvard University
    Harvard John A. Paulson School of Engineering and Applied Sciences)

  • Somenath Bakshi

    (Harvard Medical School
    Cambridge University)

  • Emanuele Leoncini

    (Harvard Medical School)

  • Lorena G. Lyon

    (Harvard Medical School)

  • Johan Paulsson

    (Harvard Medical School)

  • Pamela A. Silver

    (Harvard Medical School
    Harvard University)

Abstract

Synthetic gene oscillators have the potential to control timed functions and periodic gene expression in engineered cells. Such oscillators have been refined in bacteria in vitro, however, these systems have lacked the robustness and precision necessary for applications in complex in vivo environments, such as the mammalian gut. Here, we demonstrate the implementation of a synthetic oscillator capable of keeping robust time in the mouse gut over periods of days. The oscillations provide a marker of bacterial growth at a single-cell level enabling quantification of bacterial dynamics in response to inflammation and underlying variations in the gut microbiota. Our work directly detects increased bacterial growth heterogeneity during disease and differences between spatial niches in the gut, demonstrating the deployment of a precise engineered genetic oscillator in real-life settings.

Suggested Citation

  • David T. Riglar & David L. Richmond & Laurent Potvin-Trottier & Andrew A. Verdegaal & Alexander D. Naydich & Somenath Bakshi & Emanuele Leoncini & Lorena G. Lyon & Johan Paulsson & Pamela A. Silver, 2019. "Bacterial variability in the mammalian gut captured by a single-cell synthetic oscillator," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12638-z
    DOI: 10.1038/s41467-019-12638-z
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    Cited by:

    1. Guo, Junfeng & Wang, Fei & Xue, Qianwen & Wang, Mengqing, 2023. "Cluster synchronization control for coupled genetic oscillator networks under denial-of-service attacks: Pinning partial impulsive strategy," Chaos, Solitons & Fractals, Elsevier, vol. 177(C).
    2. Lukas Aufinger & Johann Brenner & Friedrich C. Simmel, 2022. "Complex dynamics in a synchronized cell-free genetic clock," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    3. Jung Hun Park & Gábor Holló & Yolanda Schaerli, 2024. "From resonance to chaos by modulating spatiotemporal patterns through a synthetic optogenetic oscillator," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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