A population-based temporal logic gate for timing and recording chemical events

Victoria Hsiao, Yutaka Hori, Paul W. Rothemund, Richard M. Murray

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Engineered bacterial sensors have potential applications in human health monitoring, environmental chemical detection, and materials biosynthesis. While such bacterial devices have long been engineered to differentiate between combinations of inputs, their potential to process signal timing and duration has been overlooked. In this work, we present a two-input temporal logic gate that can sense and record the order of the inputs, the timing between inputs, and the duration of input pulses. Our temporal logic gate design relies on unidirectional DNA recombination mediated by bacteriophage integrases to detect and encode sequences of input events. For an E. coli strain engineered to contain our temporal logic gate, we compare predictions of Markov model simulations with laboratory measurements of final population distributions for both step and pulse inputs. Although single cells were engineered to have digital outputs, stochastic noise created heterogeneous single-cell responses that translated into analog population responses. Furthermore, when single-cell genetic states were aggregated into population-level distributions, these distributions contained unique information not encoded in individual cells. Thus, final differentiated sub-populations could be used to deduce order, timing, and duration of transient chemical events.

Original languageEnglish
Article number12
JournalMolecular Systems Biology
Volume12
Issue number5
DOIs
Publication statusPublished - 2016 May 1

Fingerprint

Temporal logic
Logic gates
Temporal Logic
Timing
Cell
Chemical detection
Population
Population distribution
duration
Integrases
Bacteriophages
Biosynthesis
Demography
cells
Escherichia coli
Environmental Health
environmental monitoring
Environmental Monitoring
population distribution
Health Monitoring

Keywords

  • DNA memory
  • event detectors
  • integrases
  • population analysis
  • stochastic biomolecular models

ASJC Scopus subject areas

  • Medicine(all)
  • Information Systems
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics
  • Applied Mathematics

Cite this

A population-based temporal logic gate for timing and recording chemical events. / Hsiao, Victoria; Hori, Yutaka; Rothemund, Paul W.; Murray, Richard M.

In: Molecular Systems Biology, Vol. 12, No. 5, 12, 01.05.2016.

Research output: Contribution to journalArticle

Hsiao, Victoria ; Hori, Yutaka ; Rothemund, Paul W. ; Murray, Richard M. / A population-based temporal logic gate for timing and recording chemical events. In: Molecular Systems Biology. 2016 ; Vol. 12, No. 5.
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