Genetic Circuit Engineering Meets Control Theory

Domitilla Del Vecchio1

  • 1Massachusetts Institute of Technology

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Semiplenary Session

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08:30 - 09:30 | Wed 11 Dec | Apollon | WeSP1

Genetic Circuit Engineering Meets Control Theory

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Abstract

Genetic circuits control every aspect of life and thus the capability to engineer genetic circuits de-novo opens exciting possibilities, from revolutionary drugs and green energy, to bugs that recognize and kill cancer cells. The remarkable robustness of natural gene networks is the result of million years of evolution and is in sharp contrast with the fragility of synthetic genetic circuits built today. The ability of designing circuits that perform as predicted is still largely lacking because a genetic module’s input/output behavior often changes upon inserting the module into a system. This leads to a daunting design process where each component of a system needs to be redesigned every time a new piece is added. Rather than relying on such ad-hoc procedures, control theoretic approaches may be used to engineer “insulation” of circuit components from context, thus enabling modular composition through specified input/output connections. In this talk, I will give an overview of modularity failures in engineered genetic circuits. I will thus introduce a control-theoretic framework, founded on the concept of retroactivity, that addresses the insulation question by mathematically formulating a classical disturbance rejection problem. Biomolecular feedback control architectures that solve this problem through a form of integral action were used to build two devices in living cells: the load driver and the resource decoupler. These devices aid modularity, thus facilitating predictable composition of genetic circuits to create more sophisticated systems. Control theoretic approaches promise to address many pressing challenges in engineering biology.

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