Mapping behavioral specifications to model parameters in synthetic biology

Area of Science:

• Synthetic Biology
• Systems Biology
• Computational Biology

Background:

• Advancements in transcriptional part assembly enable reliable construction of synthetic biological devices.
• Standardization of biological parts facilitates in silico design and optimization.
• Optimizing kinetic parameters and protein abundances is crucial for robust device performance.

Purpose of the Study:

• To address the inverse problem of determining parameter values that satisfy design specifications for dynamical models.
• To develop a method for robustly satisfying functional specifications on model trajectories.

Main Methods:

• Linearizing the forward operator that maps parameter sets to specifications.
• Inverting the linearized operator locally to determine parameter values.
• Utilizing a dynamical model to represent device behavior.

Main Results:

• The linearization approach maps parameter intervals, not just points, to specifications.
• All obtained parameter values satisfy the design specifications by construction.
• The method offers an advantage over random sampling techniques.

Conclusions:

• The developed method enables rational forward design of synthetic biology devices.
• This approach can be integrated into pipelines for optimizing biological constructs.
• The general method enhances the reliability and predictability of synthetic biological systems.