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Researchers Create DNA Logic Circuits That Work in Test Tubes
Computers and liquids are not very compatible,
as many a careless coffee-drinking laptop owner has
discovered. But a new breakthrough by researchers at
the California Institute of Technology could result
in future logic circuits that literally work in a test
tube--or even in the human body.
In the current issue of the journal Science, a Caltech
group led by computer scientist Erik Winfree reports
that they have created DNA logic circuits that work
in salt water, similar to an intracellular environment.
Such circuits could lead to a biochemical microcontroller,
of sorts, for biological cells and other complex chemical
systems. The lead author of the paper is Georg Seelig,
a postdoctoral scholar in Winfree's lab.
"Digital logic and water usually don't mix, but
these circuits work in water because they are based
on chemistry, not electronics," explains Winfree,
an associate professor of computer science and computation
and neural systems who is also a recipient of a MacArthur
genius grant.
Rather than encoding signals in high and low voltages,
the circuits encode signals in high and low concentrations
of short DNA molecules. The chemical logic gates that
perform the information processing are also DNA molecules,
with each gate a carefully folded complex of multiple
short DNA strands.
When a gate encounters the right input molecules, it
releases its output molecule. This output molecule in
turn can help trigger a downstream gate--so the circuit
operates like a cascade of dominoes in which each falling
domino topples the next one.
However, unlike dominoes and electronic circuits, components
of these DNA circuits have no fixed position and cannot
be simply connected by a wire. Instead, the chemistry
takes place in a well-mixed solution of molecules that
bump into each other at random, relying on the specificity
of the designed interactions to ensure that only the
right signals trigger the right gates.
"We were able to construct gates to perform all
the fundamental binary logic operations--AND, OR, and
NOT," explains Seelig. "These are the building
blocks for constructing arbitrarily complex logic circuits."
As a demonstration, the researchers created a series
of circuits, the largest one taking six inputs processed
by 12 gates in a cascade five layers deep. While this
is not large by the standards of Silicon Valley, Winfree
says that it demonstrates several design principles
that could be important for scaling up biochemical circuits.
"Biochemical circuits have been built previously,
both in test tubes and in cells," Winfree says.
"But the novel thing about these circuits is that
their function relies solely on the properties of DNA
base-pairing. No biological enzymes are necessary for
their operation.
"This allows us to use a systematic and modular
approach to design their logic circuits, incorporating
many of the features of digital electronics," Winfree
says.
Other advantages of the approach are signal restoration
for the production of correct output even when noise
is introduced, and standardization of the chemical-circuit
signals by the use of translator gates that can use
naturally occurring biological molecules, such as microRNA,
as inputs. This suggests that the DNA logic circuits
could be used for detecting specific cellular abnormalities,
such as a certain type of cancer in a tissue sample,
or even in vivo.
"The idea is not to replace electronic computers
for solving math problems," Winfree says. "Compared
to modern electronic circuits, these are painstakingly
slow and exceedingly simple. But they could be useful
for the fast-growing discipline of synthetic biology,
and could help enable a new generation of technologies
for embedding 'intelligence' in chemical systems for
biomedical applications and bionanotechnology."
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