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Engineering cells,
Building circuits.
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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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