Homeostasis is a recurring theme in biology that ensures that regulated variables robustly—and often completely—adapt to environmental perturbations. This robust perfect adaptation feature is achieved in natural circuits by using integral control, a negative feedback strategy that performs mathematical integration to achieve structurally robust regulation. Despite its benefits, the synthetic realization of integral feedback in living cells has remained elusive owing to the complexity of the required biological computations. Here we discuss fundamental biomolecular controller topologies that realize such feedback and achieve robust perfect adaptation by virtue of their structure. On the basis of this concept, we demonstrate how to engineer integral feedback controllers in living cells to achieve adaptation to environmental and network perturbations. Our results provide conceptual and practical tools in the area of cybergenetics for the engineering of synthetic self-adapting genetic circuits, with potential applications in industrial biotechnology and cell therapy.
Dr. Khammash is Professor of Control Theory and Systems Biology in the Department of Biosystems Science and Engineering (D-BSSE) at ETH-Zurich. He received his B.S. degree from Texas A & M University in 1986 and his Ph.D. from Rice University in 1990, both in Electrical Engineering. In 1990, he joined the Electrical Engineering Department at Iowa State University. While at Iowa State University, he created the Dynamics and Control Program and led that control group until 2002, when he became a member of the Mechanical Engineering faculty at the University of California, Santa Barbara. In Santa Barbara, he served as Vice Chair of the Mechanical Engineering Department from 2003 to 2006 and as the Director of the Center for Control, Dynamical Systems and Computation from 2005 to 2011. In 2011 Prof. Khammash moved with his group to Switzerland, joining the Department of Biosystems Science and Engineering at ETH Zurich.
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