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Figure 4.2 A simplified view of the two cases for a biochemical inverter. Here, the
concentration of a particular messenger RNA (mRNA) molecule represents a logic
signal. In the first case, the input mRNA is absent and the cell transcribes the gene for
the output mRNA. In the second case, the input mRNA is present and the cell trans-
lates the input mRNA into the input protein. The input protein then binds specifically
to the gene at the promoter site (labeled P) and prevents the cell from synthesizing the
output mRNA.
signal represents the digital value better than the analog input signal. Engi-
neers carefully combine these reliable components into complex systems that
perform reliable computation. Experimental results in chapter 7 describe in
vivo digital-logic circuits with good noise margins and signal restoration to
demonstrate the feasibility of programming cells using digital computation. In
the study of existing biological organisms, recent work [7-9, 13] suggests that
cells routinely use digital computation to make certain decisions that result in
binary on/off behavior. Because the digital abstraction is both convenient to
use and feasible, it offers a useful paradigm for programming cells and cell
aggregates. However, much like desktop computers use both digital and analog
components, in the future we will also incorporate analog logic elements into
engineered biological systems as the analog components become necessary for
particular tasks.
To create novel biological systems, an engineer must be equipped with de-
sign and modeling software that prescribes how primitive components may be
combined into complex systems with predictable and reproducible behavior.
We present BioSPICE, a prototype tool that helps biocircuit designers manage
the complexity of the substrate and achieve reliable systems. The inspiration
for BioSPICE comes from the utility of tools such as SPICE [10] in the design
of electrical circuits. BioSPICE supports both static and dynamic analysis of
single-cell environments and small cell aggregates.
 
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