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

Area of Science:

• Synthetic Biology
• Microbial Engineering
• Biochemical Engineering

Background:

• Bacterial sensors are valuable for health monitoring, environmental detection, and biosynthesis.
• Existing bacterial devices primarily focus on input combinations, neglecting temporal signal processing.
• Signal timing and duration processing remains an underexplored area in engineered bacterial systems.

Purpose of the Study:

• To develop a novel two-input temporal logic gate for engineered bacteria.
• To enable bacterial sensors to process signal order, timing, and duration.
• To encode transient chemical events using bacterial genetic circuits.

Main Methods:

• Designed a temporal logic gate utilizing unidirectional DNA recombination mediated by bacteriophage integrases.
• Engineered an Escherichia coli (E. coli) strain to host the temporal logic gate.
• Compared Markov model simulations with laboratory measurements of population distributions for step and pulse inputs.

Main Results:

• The engineered E. coli strain successfully sensed and recorded input order, timing, and duration.
• Stochastic noise resulted in heterogeneous single-cell responses, leading to analog population-level responses.
• Aggregated population distributions contained unique information beyond individual cell states, allowing deduction of transient chemical events.

Conclusions:

• Engineered bacterial temporal logic gates can accurately process complex temporal information.
• Population-level analysis of heterogeneous cellular responses provides insights into transient chemical events.
• This work expands the capabilities of bacterial sensors for sophisticated signal processing.