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

Autor: Riglar DT; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Department of Infectious Disease, Imperial College London, London, UK., Richmond DL; Image and Data Analysis Core, Harvard Medical School, Boston, MA, USA., Potvin-Trottier L; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.; Biology Department, Concordia University, Montreal, QC, Canada., Verdegaal AA; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Naydich AD; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA., Bakshi S; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.; Department of Engineering, Cambridge University, Cambridge, UK., Leoncini E; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Lyon LG; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Paulsson J; Department of Systems Biology, Harvard Medical School, Boston, MA, USA., Silver PA; Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Pamela_Silver@hms.harvard.edu.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. Pamela_Silver@hms.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Oct 11; Vol. 10 (1), pp. 4665. Date of Electronic Publication: 2019 Oct 11.
DOI: 10.1038/s41467-019-12638-z
Abstrakt: 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.
Databáze: MEDLINE