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resulting from gate couplings and only select proteins that achieve satisfactory
levels of these factors.
Chapter 7 describes measurements and genetic modifications of in vivo logic
gates to obtain components with the desired behavior for constructing complex
and reliable circuits.
CONCLUSIONS
This chapter lays the foundation of an engineering discipline for obtaining com-
plex, predictable, and reliable cell behaviors by embedding biochemical logic
circuits and programmed intercellular communications into cells. To accom-
plish this goal, this chapter provides a well-characterized cellular gate library,
a biocircuit design methodology, and software design tools. The cellular gate
library includes biochemical gates that implement the NOT, IMPLIES, and
AND logic functions in E. coli cells.
We introduced a biocircuit design methodology that comprises a mechanism
for measuring the device physics of gates and criteria for evaluating, modifying,
and matching gates based on their steady-state behavior. By using the abstrac-
tion of logic circuits, complex and reliable behavior is synthesized from reliable,
well-characterized components with matching input/output characteristics.
In addition to the above contributions, we have developed BioSPICE, a
prototype software tool for biocircuit design. BioSPICE simulates in vivo logic
circuits using ordinary differential equations that model biochemical rate equa-
tions. The kinetics for the rate constants were derived from the literature and
yield simulation results that predict the behavior of engineered biocircuits.
BioSPICE simulations of modified rate constants illustrate the effects on the
static and dynamic behavior of the circuits and serve as motivation for geneti-
cally modifying components in laboratory experiments.
References
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coli and Salmonella , 2nd ed., pages 902-908. ASM Press, Washington, DC, 1992.
[3] H. A. Greisman and C. O. Pabo. A general strategy for selecting high-affinity zinc
finger proteins for diverse dna target sites. Science , 275:657-661, 1997.
[4] R. W. Hendrix. Lambda II . Cold Spring Harbor Laboratory Press, Cold Spring
Harbor, NY, 1983.
[5] A. Hjelmfelt, E. D. Weinberger, and J. Ross. Chemical implementation of neural
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