Design and Implementation of a Biomolecular Circuit for Tracking Protein Concentration

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Emmanuel L. C. de los Santos*, Victoria Hsiao* and Richard M. Murray
Presented, 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.