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proteins and their associated operators and generates genetic logic circuits di-
rectly from gate-level descriptions. Contrast this modularity with the method
of Hjelmfelt et al. [5], which requires proteins that modify other proteins and
where all signals are protein concentrations. In that case, the resulting physico-
chemical interdependence of successive logic stages makes simple modularity
almost impossible.
Implementation of Combinatorial Logic
The approach to combinatorial logic is to “wire-OR” the outputs of multiple in-
verters by assigning them the same output gene. The output mRNA is expressed
in the absence of either input mRNAs, and is not be expressed only when both
inputs are present. This configuration implements a NAND gate. Because the
performance of a NAND gate relies solely on that of its constituent inverters,
well-engineered inverters will yield well-engineered combinatorial gates.
Figure 4.6 illustrates a small circuit where a NAND gate connects to an
inverter. Here, mRNA and their corresponding proteins serve as the logic cir-
cuit wires, while the promoter and protein/mRNA decay implement the gates.
Because a NAND gate is a universal logic element and can be wired to other
gates, any finite digital circuit can be built within practical limitations such as
the number of distinct signal proteins available.
Choice of Signals
The library of naturally available signal proteins includes approximately a few
thousand candidates. Any repressor protein with sufficiently cooperative DNA
binding that does not interfere with normal cell operation is a potential can-
didate. The experiments described in chapter 7 use four different naturally
occurring DNA binding proteins and their operators, as well as several novel
mutations to one of the operators. The number of naturally occurring proteins
that could potentially serve as signals may never limit biocircuit construction
because other factors, such as the metabolic capabilities of cells, are likely to
place lower limits on biocircuit complexity within a single cell. However, it
Figure 4.6
A logic circuit and its DNA implementation: The wire-OR of the outputs
of two genes implements a NAND gate, and the choice of the output gene determines
the gate connectivity.
