In silico control of biomolecular processes

Area of Science:

• Synthetic Biology
• Systems Biology
• Biotechnology

Background:

• Precise control of gene expression is crucial for understanding cellular dynamics and engineering biological systems.
• Existing methods often lack the quantitative accuracy and long-term stability required for complex applications.

Purpose of the Study:

• To develop and demonstrate a real-time, closed-loop control platform for gene expression in yeast.
• To achieve quantitative and long-term control of protein levels at both population and single-cell levels.

Main Methods:

• Integration of microscopy for cell-level monitoring, microfluidics for environmental manipulation, and custom software for automated control.
• Utilized an endogenous osmo-stress responsive promoter and manipulated external osmolarity for feedback control.

Main Results:

• Demonstrated successful long-term closed-loop control of gene expression in yeast.
• Achieved precise regulation for both constant and time-varying target protein profiles.
• Validated control at both the population and single-cell levels.

Conclusions:

• The developed platform offers a robust method for tightly controlling gene expression over extended periods.
• This system provides a valuable tool for quantitative biological research and synthetic biology applications.
• Enables precise manipulation of cellular functions and the construction of complex engineered biological networks.