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Cell

Title:		Real-Time Genetic Compensation Defines the Dynamic Demands of Feedback Control
Author(s):		Harrigan P; Madhani HD; El-Samad H;
Address:		"Department of Biochemistry and Biophysics, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA. Department of Biochemistry and Biophysics, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Chan-Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: hitenmadhani@gmail.com. Department of Biochemistry and Biophysics, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Chan-Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: hana.el-samad@ucsf.edu"
Journal Title:		Cell
Year:		2018
Volume:		175
Issue:		3
Page Number:		877 - 886
DOI:		10.1016/j.cell.2018.09.044
ISSN/ISBN:		1097-4172 (Electronic) 0092-8674 (Print) 0092-8674 (Linking)
Abstract:		"Biological signaling networks use feedback control to dynamically adjust their operation in real time. Traditional static genetic methods such as gene knockouts or rescue experiments can often identify the existence of feedback interactions but are unable to determine what feedback dynamics are required. Here, we implement a new strategy, closed-loop optogenetic compensation (CLOC), to address this problem. Using a custom-built hardware and software infrastructure, CLOC monitors, in real time, the output of a pathway deleted for a feedback regulator. A minimal model uses these measurements to calculate and deliver-on the fly-an optogenetically enabled transcriptional input designed to compensate for the effects of the feedback deletion. Application of CLOC to the yeast pheromone response pathway revealed surprisingly distinct dynamic requirements for three well-studied feedback regulators. CLOC, a marriage of control theory and traditional genetics, presents a broadly applicable methodology for defining the dynamic function of biological feedback regulators"
Keywords:		"*Feedback, Physiological *Gene Expression Regulation, Fungal Genetic Complementation Test/methods Mating Factor/genetics/metabolism Optogenetics/*methods Saccharomyces cerevisiae/genetics Software Transcriptional Activation closed-loop control feedback op;"
Notes:		"MedlineHarrigan, Patrick Madhani, Hiten D El-Samad, Hana eng R01 AI120464/AI/NIAID NIH HHS/ R01 GM071801/GM/NIGMS NIH HHS/ T32 EB009383/EB/NIBIB NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2018/10/20 Cell. 2018 Oct 18; 175(3):877-886.e10. doi: 10.1016/j.cell.2018.09.044"