1 Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
2 Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
3 Department of Infectious Disease, Imperial College London, London, UK.
4 Image and Data Analysis Core, Harvard Medical School, Boston, MA, USA.
5 Biology Department, Concordia University, Montreal, QC, Canada.
6 Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA.
7 Department of Engineering, Cambridge University, Cambridge, UK.
8 Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Pamela_Silver@hms.harvard.edu.
9 Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. Pamela_Silver@hms.harvard.edu.

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

Nat Commun. 2019 Oct 11;10(1):4665

Authors: Riglar DT, Richmond DL, Potvin-Trottier L, Verdegaal AA, Naydich AD, Bakshi S, Leoncini E, Lyon LG, Paulsson J, Silver PA

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.

PMID: 31604953 [PubMed - in process]