Information Technology Reference
In-Depth Information
INFORMATION PROCESSING IN CELLS
Information Processing with Natural Genetic Circuits
Gene expression profiling, which provides powerful analyses of transcriptional
responses to cellular perturbation and interconnectivity among gene regulation
in transcription, represents one important use of the information processing
functionality of cells. Most often this is performed by screening isolated mRNA
using cDNA microarrays. Uses of this technology have included analyses un-
covering the consequences of individual mutations [34], understanding cellular
physiology under various conditions [55], examining disease states [33], and
measuring responses to pharmaceuticals [67] and crop protection products [56].
However, there are important limitations to these microarray methods, partic-
ularly for the types of systems considered here. First, the mRNA isolation step
would be difficult to implement in a small, low-power, and automated manner.
Furthermore, artifacts may arise during the RNA isolation [104] or from cross-
hybridization [85]. And finally, as a destructive measurement, only a single
snapshot in time of the expression profile can be obtained.
An important alternative to genome-wide expression profiling uses reporter
gene fusions. Transcriptional fusions have been widely used [60, 92] because
they can be straightforwardly produced [17], identified, and assayed [58, 112].
Reporter genes are described in more detail in the next section. Recently, the
identification and mapping of a large number of random
Escherichia coli
DNA
fragments fused to luminescent reporter genes was reported [110]. The result
was a genome-wide, genome-registered collection of
Escherichia coli
biolu-
minescent reporter gene fusions that mirrors the transcriptional wiring diagram
of
E. coli
. Information enters the cells through interaction with the genetic
regulatory machinery, is processed by the existing genetic circuits, and discrete
outputs are generated by reporter gene expression. While presenting many of
the same advantages, this collection of intact whole-cell components avoids
many of the disadvantages of the DNA microarray technology. In particular, no
RNA extraction or similar manipulation is required, and rather than a snapshot,
a time history of gene expression (or at least protein activity) is generated.
Silicon Mimetic Approach
While the genome-wide, genome-registered
E. coli
collection described above
provides an important tool for using the information processing capabilities of
whole cells, only the natural genetic circuits and wiring of these cells is used.
We describe here what we have coined the “silicon mimetic” approach, where
genetic circuit functionality is engineered to perform functions analogous to
those found in man-made systems.
Silicon semiconductor technology is the gold standard of man-made in-
formation processing devices and systems. In such devices, information is
