Store, Exchange, and Interact with Synthetic Biological Data

Cell Logic

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. Cello is a framework that describes 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.

Cello converts electronic design specifications of combinational logic to complete DNA sequences encoding transcriptional logic circuits that can be executed in bacterial cells. A database of transcriptional repressors characterized in the Voigt lab provide genetic NOT gates and NOR gates that can be composed into any logic function.

The automated workflow and in-house genetic gates will make circuit design more reproducible and broadly accessible to biological engineering labs.

Key Features

  • Generates a Boolean circuit as a Directed Acyclic graph from an HDL specification (Verilog).

  • Uses a database of second-generation genetic logic gates whose transfer functions are insulated from promoter context.

  • Allows users to upload custom UCF (User Constraint file) files.

  • Searches for the optimal assignment of transcriptional repressors to NOT/NOR gates by signal matching with the experimentally measured transfer functions.

  • Offers a wide range of assignment algorithms including Simulated annealing (default), Hill climbing, Breadth first search, Random permutations,etc.

  • Generates histograms for predicted gate REU for each row of the truth table for the best genetic circuit assignment.

  • Generates multiple plasmid versions using the Eugene language for constrained combinatorial enumeration of transcriptional unit orders and orientations.

  • Allows external applications to connect to Cello using a REST API.

Funding

  • Life Technologies (a Thermo Fisher brand): A114510

  • Office of Naval Research: Multidisciplinary University Research Initiative grant N00014-13-1-0074

  • Siebel Scholarship: Class of 2015

  • Air Force Office of Scientific Research: National Defense Science and Engineering Graduate fellowship FA9550-11-C-0028

  • National Institute of General Medical Sciences: P50 GMO98792

  • National Science Foundation

    • Synthetic Biology Engineering Research Center grant SynBERC EEC0540879

    • NSF grant 1147158

  • NIST Strategic and Emerging Research Initiative

  • National Research Council postdoctoral program

  • AWS in Education Grant

Cello is free to use. See the CAD website and GitHub located below:

Screen Shots

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