" Toward System-level Control of Complex Biological Systems "
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Abstract: In the past decades, there has been great advancement in bio, nano, and information technology.  Bio and nanotechnologies facilitate modifications, manipulations, and characterizations of different biological objects down to the single molecule level.  On the other hand, information technology provides the framework for controlling and understanding complex biomolecular systems.  Fusion of these technologies enables us to take innovative approaches to explore the fundamental design rules in cells.  With a closed-loop optimization modality to circumvent the need for detailed information of biological signaling and regulatory networks, we demonstrate cellular induction towards a desired phenotypic response by efficiently searching through a large parametric space of biochemical effectors.  More specifically, we utilized a combination of six cytokines to regulate the activity of NF-kB (nuclear factor kappa B) in 293T human embryonic kidney cells.  Only tens of tests out of one million possible trials were needed to ascertain the most potent combination of these cytokines using a stochastic search algorithm in the feedback loop.  The scheme possesses the potential of being a generic platform with broad applicabilities to control a wide class of cells and biological systems.