Low-Burden Biological Feedback Controllers for Near-Perfect Adaptation

Area of Science:

• Synthetic Biology
• Control Engineering
• Biochemical Engineering

Background:

• Synthetic biological systems require robust control for reliability.
• Adaptation (disturbance rejection) is crucial for maintaining constant output despite cellular noise or external perturbations.
• Traditional engineering control architectures can inspire synthetic biological designs.

Purpose of the Study:

• To propose and analyze a novel feedback control architecture for synthetic biology.
• To achieve near-perfect adaptation to variations in transcription and translation rates.
• To design a system that minimizes cellular resource consumption.

Main Methods:

• Utilized integrase and excisionase proteins for DNA inversion.
• Incorporated an mRNA-mRNA annihilation reaction.
• Modeled the system using deterministic and stochastic simulations.

Main Results:

• The proposed system functions as a three-mode switching controller.
• Demonstrated near-perfect adaptation to variations in transcription and translation rates.
• Analyzed steady-state behavior and derived operating range limits.

Conclusions:

• The developed control architecture enhances the robustness and reliability of synthetic biological systems.
• The system effectively achieves adaptation without excessive resource utilization.
• The study provides a foundation for implementing advanced control strategies in synthetic biology.