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

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Oct 11, 2019
Source ID
10.1038/s41467-019-12638-z

Entities

People

  • Alexander D. Naydich
  • Andrew A. Verdegaal
  • David L Richmond
  • David T Riglar
  • Emanuele Leoncini
  • Johan Paulsson
  • Laurent Potvin-Trottier
  • Lorena G. Lyon
  • Pamela Silver
  • Somenath Bakshi

Organizations

  • Harvard Medical School
  • United States Department of Defense
  • Wyss Institute for Biologically Inspired Engineering

Tags

Fields of Study

  • Biology

Readers

  • Gulf War Illness and Chronic Multisymptom Illness in Veterans.
  • Molecular and genetic basis of cancer.
  • Systems Analysis and Design

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech