title: Synthetic circuits integrating logic and memory in living cells.
abstract: Logic and memory are essential functions of circuits that generate complex, state-dependent responses. Here we describe a strategy for efficiently assembling synthetic genetic circuits that use recombinases to implement Boolean logic functions with stable DNA-encoded memory of events. Application of this strategy allowed us to create all 16 two-input Boolean logic functions in living Escherichia coli cells without requiring cascades comprising multiple logic gates. We demonstrate long-term maintenance of memory for at least 90 cell generations and the ability to interrogate the states of these synthetic devices with fluorescent reporters and PCR. Using this approach we created two-bit digital-to-analog converters, which should be useful in biotechnology applications for encoding multiple stable gene expression outputs using transient inputs of inducers. We envision that this integrated logic and memory system will enable the implementation of complex cellular state machines, behaviors and pathways for therapeutic, diagnostic and basic science applications.
authors: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Piro
authors: P
authors: Siuti
authors: John
authors: J
authors: Yazbek
authors: Timothy K
authors: TK
authors: Lu
mesh_terms: D058045:Artificial Cells; D016248:Computer Storage Devices; D039301:Computers, Molecular; D004867:Equipment Design; D019544:Equipment Failure Analysis; D004926:Escherichia coli / Q000235:genetics*; D005818:Genetic Engineering / Q000379:methods*; D012815:Signal Processing, Computer-Assisted / Q000295:instrumentation*; D058615:Synthetic Biology; D018511:Systems Integration
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