From a discrete to continuous actuation for improved real-time control of gene expression in mammalian cells

Abstract: Real-time automatic regulation of gene expression is a key technology for synthetic biology enabling, for example, synthetic circuit components to operate in an optimal range. We show that it is possible to regulate the expression of a reporter protein from the tetracycline-inducible promoter in a population of mammalian cells using principles from automatic control engineering. We demonstrate that the performance of the control experiments improves by moving from a discrete to a continuous actuation. Our automated control platform is an innovative tool to enable dose-response studies of small molecules and investigation of gene dosage effects in disease.