Design and Implementation of a Biomolecular Circuit for Tracking Protein Concentration

Emmanuel L. C. de los Santos, Victoria Hsiao and Richard M. Murray
2013 American Control Conference (ACC)

This paper describes the design, modeling, synthesis and preliminary validation of a protein concentration regulator circuit. The circuit is designed to maintain the level of a target protein to a reference level, specified by the amount of another protein. This is implemented using a single negative feedback loop that inhibited the production of the target protein once its concentration was equal to the reference amount. A mathematical model consisting of a set of ODEs is derived from mass action laws and Hill function approximations of protein production. Steady-state analysis of the model is used to predict parameter sensitivity and experimental behavior. We implemented this circuit in E. coli using scaffold-based sequestration and transcriptional activation. Preliminary experimental results show the system matching predictions from our model and performing the expected task.

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