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For obtaining coordinated aggregate cell behavior, we demonstrate pro-
grammed cell-to-cell communications using chemical diffusion to carry mes-
sages. Multicellular organisms create complex patterned structures from
identical, unreliable components. This process of differentiation relies on
communications between the cells that compose the system. Learning how
to engineer such robust behavior from aggregates is important for better un-
derstanding distributed computing, for better understanding the natural de-
velopmental process, and for engineering novel multicellular organisms with
well-defined behaviors. Chemical diffusion is one of several communication
mechanisms that can help achieve coordinated behavior in cell aggregates.
In this chapter, the next section introduces the logic gates we implemented
in cells. The NOT gate is the fundamental building block for constructing
intracellular circuits, and the IMPLIES and AND gates are used for intercellular
communications. The third section introduces the BioSPICE tool for biocircuit
design and analysis. The section describes the model used for simulating a
biochemical inverter, simulations of simple logic circuits in single cells, and
analysis of genetic modifications to achieve the desired gate behavior.
CELLULAR GATES
A fundamental chemical process in the cell is the production of proteins from
genes encoded in the DNA. The cell performs important regulatory activities
through DNA-binding proteins that repress or activate the production of specific
proteins. Repression can be used to implement digital-logic inverters [6]. This
section presents a formal model of this inversion mechanism and explains how
to construct any finite digital-logic circuit using these inverters.
In this section we also introduce two additional logic gates that implement
the IMPLIES and AND logic functions. The inputs to these gates are mRNA
molecules that code for DNA-binding proteins and small inducer molecules
that affect the activity of these proteins. Because the inducer molecules freely
diffuse through cell membranes, these two gates are useful for intercellular
communications and other external interactions with the in vivo circuits.
A Biochemical Inverter
Natural gene regulation systems exhibit characteristics useful for implementing
in vivo logic circuits. Figure 4.2 presents a simplified view of the two states
in the biochemical process of inversion in either the presence or absence of
the input mRNA signal. Figure 4.3 shows a more detailed description of the
inversion process, including the role of transcription and translation.
Figure 4.4 illustrates the functional construction of an inverter from its bio-
chemical reaction stages. Let
ψ A denote the concentration level of the input
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