Architectures for Combined Transcriptional and Translational Resource Allocation Controllers

Area of Science:

• Synthetic biology
• Systems biology
• Metabolic engineering

Background:

• Competition for gene expression resources can degrade synthetic cellular circuitry performance.
• Separate transcriptional and translational controllers enhance modularity and performance.
• Orthogonal circuit-specific gene expression machinery is key to controller function.

Purpose of the Study:

• Investigate advantages, challenges, and design trade-offs of combining transcriptional and translational controllers into dual resource allocation control systems.
• Analyze candidate architectures for direct design of dual resource allocation controllers.
• Propose modifications to improve performance and robustness of dual controllers.

Main Methods:

• Analysis of candidate architectures for dual resource allocation control systems.
• Modification of designs to enhance decoupling and expression levels.
• Construction and evaluation of dual controllers using orthogonal gene expression resources.

Main Results:

• Separately functional transcriptional and translational controllers cannot be directly combined without redesign.
• Dual resource allocation controllers can be designed using only orthogonal gene expression resources.
• Proposed modifications improve performance and robustness of dual controller designs.

Conclusions:

• Dual resource allocation control systems offer superior performance and robustness compared to standalone controllers.
• Careful design and integration of orthogonal components are crucial for effective dual control.
• This work provides a framework for building more robust and efficient synthetic cellular circuits.