Genetic circuit design automation

Abstract

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 forEscherichia 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.

Synthetic DNA Synthesis and Assembly: Putting the Synthetic in Synthetic Biology

“…To date, there have been a handful of moonshot demonstrations such as the complete synthesis of an entire yeast chromosome (Annaluru et al 2014), an entire bacterial genome (Gibson et al 2008a), and the subsequent synthesis of a minimal bacterial genome (Hutchison et al 2016), which illustrate the use of synthetic DNA and the capabilities of existing gene synthesis methods to accomplish largescale synthetic biology efforts. These examples, when combined with numerous projects in which synthetic DNA has been used to evaluate functional biological components (Salis et al 2009;Callura et al 2012;Brophy and Voigt 2016), create synthetic vaccines (Dormitzer et al 2013), and construct synthetic genetic circuits (Salis et al 2009;Sowa et al 2015;Nielsen et al 2016;Rubens et al 2016) and when applied to wholesale genomic editing (Wang et al 2009;Doudna and Charpentier 2014), point to a future where the nuances of biological function can in part be understood by the design, synthesis, and assay of interchangeable synthetic components akin to synthetic drug development.…”

Strong Turing Completeness of Continuous Chemical Reaction Networks and Compilation of Mixed Analog-Digital Programs

“…The concept of biochemical computation and compilation can also be experimented in vitro and in vivo, either in Synthetic Biology, through the modification and reprogramming of living cells [35,18], or in Synthetic Biochemistry, through the creation and programming of non-living microfluidic vesicles [19], with various applications including the design of biomarkers [18].…”

Correction

“…Voigt, working with Douglas Densmore, an electrical engineer at Boston University has developed a tool called Cello (cellocad.org) to make that possible. Researchers specify genetic-circuit designs in a programming language called Verilog, and Cello produces the DNA sequences that are required to make them work 9 .…”