Feed-forward loop improves the transient dynamics of an antithetic biological controller

Area of Science:

• Synthetic biology
• Biomolecular engineering
• Systems biology

Background:

• Integral controllers are crucial for industrial adaptation to disturbances.
• Biomolecular integral controllers, like the antithetic integral controller, are used for precise gene expression regulation.
• Challenges exist in optimizing transient dynamics and adaptation for synthetic biological controllers.

Purpose of the Study:

• To investigate RNA-based biological controllers by modifying the antithetic integral controller.
• To improve transient dynamics and adaptation performance using natural feed-forward loops (FFLs).
• To explore design principles for enhanced gene expression regulation.

Main Methods:

• Model-based analysis of modified antithetic integral controllers.
• Incorporation of type-1 incoherent feed-forward loops (FFLs).
• Investigation of kinetic parameters, including degradation and transcription rates.

Main Results:

• The base antithetic controller demonstrates strong responsiveness and adaptation to disturbances.
• Integrating a type-1 incoherent FFL attenuates transient dynamics from stimuli changes.
• The FFL incorporation effectively mitigates undesired overshoot in output gene expression.

Conclusions:

• Modifying the antithetic integral controller with FFLs offers improved performance in gene expression regulation.
• Degradation and transcription rates of circuit RNA species are key determinants of controller performance.
• This study provides insights into designing robust synthetic biological controllers.