Mathematical model of a serine integrase-controlled toggle switch with a single input

Area of Science:

• Synthetic Biology
• Genetic Engineering
• Biotechnology

Background:

• Dual-state genetic switches are crucial for memory and gene expression control in synthetic biology.
• Transcriptional toggle switches (TTS) and DNA inversion switches (using serine integrases) are existing methods but require two inputs.
• A need exists for a more efficient, single-input binary switch.

Purpose of the Study:

• To design and model a robust one-input binary switch by combining a TTS and a DNA inversion switch.
• To achieve reliable switching between two states using a single input signal.
• To assess the switch's stability against parameter variations and molecular noise.

Main Methods:

• Mathematical modeling was employed to design the combined circuit.
• Integration of a transcriptional toggle switch (TTS) with a DNA inversion switch.
• Utilized unidirectional integrase-RDF-mediated recombination via a fusion protein.

Main Results:

• Successfully designed a robust one-input binary switch.
• The switch reliably alternates between two states upon receiving a single input pulse.
• Demonstrated stability against parameter variations and molecular noise, confirming robustness.

Conclusions:

• The developed one-input binary switch is a stable and robust genetic circuit.
• This switch is a promising basic element for constructing binary counting devices in synthetic biology.
• Offers a simplified control mechanism compared to previous two-input systems.