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Genetic circuit design automation
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Journal Article
Genetic circuit design automation
2016
Overview
As synthetic biology techniques become more powerful, researchers are anticipating a future in which the design of biological circuits will be similar to the design of integrated circuits in electronics. Nielsen et al. describe what is essentially a programming language to design computational circuits in living cells. The circuits generated on plasmids expressed in Escherichia coli required careful insulation from their genetic context, but primarily functioned as specified. The circuits could, for example, regulate cellular functions in response to multiple environmental signals. Such a strategy can facilitate the development of more complex circuits by genetic engineering. Science , this issue p. 10.1126/science.aac7341 A programming language is devised for biological regulatory circuits. Computation can be performed in living cells by DNA-encoded circuits that process sensory information and control biological functions. Their construction is time-intensive, requiring manual part assembly and balancing of regulator expression. We describe a design environment, Cello, in which a user writes Verilog code that is automatically transformed into a DNA sequence. Algorithms build a circuit diagram, assign and connect gates, and simulate performance. Reliable circuit design requires the insulation of gates from genetic context, so that they function identically when used in different circuits. We used Cello to design 60 circuits for Escherichia coli (880,000 base pairs of DNA), for which each DNA sequence was built as predicted by the software with no additional tuning. Of these, 45 circuits performed correctly in every output state (up to 10 regulators and 55 parts), and across all circuits 92% of the output states functioned as predicted. Design automation simplifies the incorporation of genetic circuits into biotechnology projects that require decision-making, control, sensing, or spatial organization.
