Information Technology Reference
In-Depth Information
that implements a one-bit memory using two repressible promoters arranged in
a mutually inhibitory network. A significant challenge still remains to develop
genetic circuits that make more efficient use of the memory capacity of the cell's
DNA. Likewise, Elowitz and Leibler [35] implemented a genetic clock circuit in
E. coli
with a typical period of hours. Such genetic constructs might eventually
be useful for clocking simple sequential circuits in whole cells. However, for
now this clock displays noise and cell-to-cell variations that make its use in
functional logic circuits problematic.
Noise and Random Processes in Cellular
Information-Processing Systems
Information processing through genetic circuits is subject to stochastic pro-
cesses leading to variability in response to apparently identical stimuli. This
is not a concern for cells deployed as bulk components, as the response is
averaged over a large population of cells. However, in complex systems where
the response of individual or small collections of cells becomes important, the
stochastic nature of gene regulation must be considered and incorporated into
models and simulations to enable design.
Biochemical reactions function as components in highly organized and regu-
lated networks, not as isolated processes. Cellular signals control the transcrip-
tional events that lead eventually to translation of these genes into proteins at
the first level within these networks. Some of these proteins will be regulatory
and will affect the transcription of additional genes. All of these molecules
have a dynamic half-life that determines the time of their effectiveness within
the network. The response interval between these cellular events is determined
by the time required for concentrations of each component in the network to
increase or decrease to their effective concentration ranges. In other words, a
finite period of time is required for an effector to reach an operational concen-
tration and, likewise, a certain period of time is required for that effector to
decay below the operational concentration [69].
Experimental evidence of variability both in molecular concentrations and
response time interval suggests a degree of random fluctuation at the macro
level characteristic of the processes that occur in all chemical reactions at the
micro level. The result at the macro level is that the outcomes of genetic net-
works are not entirely deterministic [2]. A corollary to this is that population-
averaged variations in gene expression are due to changes in the frequency of
full gene induction in individual cells rather than to uniform variations in gene
expression across the entire population. The term
stochastic
has been applied
to these fluctuations implying statistical variability [69]. These stochastic pro-
cesses produce noise in the genetic circuits discussed here. The result could
be nothing worse than small predictable variations from average responses in
linear circuits. However, in more complex, nonlinear circuits involving genetic
