Cells sense their environment, process information, and continuously react to both internal and external stimuli. The construction of synthetic gene networks can help improve our understanding of such naturally existing regulatory functions within cells. Synthetic gene networks will also enable a wide range of new programmed cells applications. We use computer engineering principles of abstraction, composition, and interface specifications to program cells with sensors and actuators precisely controlled by analog and digital logic circuitry. Here, recombinant DNA-binding proteins represent signals, and recombinant genes perform the computation by regulating protein expression. We constructed synthetic gene networks that implement biochemical logic circuits in Escherichia coli fabricated using the AND, NOT, and IMPLIES logic gates. We have built a variety of circuits, including a transcriptional cascade whose digital behavior improves significantly with the addition of genetic components. We have also built analog circuits that perform signal processing to detect specific chemical gradients and generate pulses in response to cell-cell communication. The integration of digital and analog circuitry is useful for controlling the behavior of individual cells and we have also combined these circuits with engineered cell-cell communication to coordinate the behavior of cell aggregates.
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