Abstract
Synthetic genetic circuits offer the potential to wield computational control over biology, but their complexity is limited by the accuracy of mathematical models. Here, we present advances that enable the complete encoding of an electronic chip in the DNA carried by Escherichia coli (E. coli). The chip is a binary‐coded digit (BCD) to 7‐segment decoder, associated with clocks and calculators, to turn on segments to visualize 0–9. Design automation is used to build seven strains, each of which contains a circuit with up to 12 repressors and two activators (totaling 63 regulators and 76,000 bp DNA). The inputs to each circuit represent the digit to be displayed (encoded in binary by four molecules), and output is the segment state, reported as fluorescence. Implementation requires an advanced gate model that captures dynamics, promoter interference, and a measure of total power usage (RNAP flux). This project is an exemplar of design automation pushing engineering beyond that achievable “by hand”, essential for realizing the potential of biology.
Highlights
Encoding algorithms in DNA would allow cells to be programmed to follow a set of rules or perform problem-solving operations (Khalil & Collins, 2010; Benenson, 2012; Brophy & Voigt, 2014; Purcell & Lu, 2014; Bojar & Fussenegger, 2016). This requires the introduction of synthetic regulatory networks, known as “genetic circuits”, that control when genes are turned on and off
This study introduces a gate model that requires little additional parameterization, but captures non-additive effects between input promoters, dynamics, and the utilization of cellular resources that can lead to slow growth and evolutionary breakage
Larger design projects can be undertaken, which we demonstrate by recoding an entire binary-coded digit (BCD) to 7segment decoder chip
Summary
Encoding algorithms in DNA would allow cells to be programmed to follow a set of rules or perform problem-solving operations (Khalil & Collins, 2010; Benenson, 2012; Brophy & Voigt, 2014; Purcell & Lu, 2014; Bojar & Fussenegger, 2016). For example Cello, allows a user to define a desired function, for which algorithms combine gates to build a circuit and encode it in DNA. Central to this software is the quality of the mathematical model describing the gates, which is used to predict how they will perform when connected. The parameters correspond to those used to calculate b (equation 3) Arrows indicate those promoter states producing RNAP flux. Two NOT gates based on the AmtR (top) and PhlF (bottom) repressors are shown Their output promoters occupy the upstream (position 1) and downstream (position 2) inputs to the OR gate, respectively.
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