Largest biochemical circuit built out of small
synthetic DNA molecules
2 June 2011, by Marcus Woo
circuits would give biochemists unprecedented
control in designing chemical reactions for
applications in biological and chemical engineering
and industries. For example, in the future a
synthetic biochemical circuit could be introduced
into a clinical blood sample, detect the levels of a
variety of molecules in the sample, and integrate
that information into a diagnosis of the pathology.
"We're trying to borrow the ideas that have had
huge success in the electronic world, such as
abstract representations of computing operations,
programming languages, and compilers, and apply
them to the biomolecular world," says Lulu Qian, a
senior postdoctoral scholar in bioengineering at
Caltech and lead author on a paper published in
the June 3 issue of the journal Science.
Along with Erik Winfree, Caltech professor of
computer science, computation and neural
systems, and bioengineering, Qian used a new kind
of DNA-based component to build the largest
artificial biochemical circuit ever made. Previous labmade biochemical circuits were limited because
they worked less reliably and predictably when
scaled to larger sizes, Qian explains. The likely
reason behind this limitation is that such circuits
In many ways, life is like a computer. An
need various molecular structures to implement
organism's genome is the software that tells the
different functions, making large systems more
cellular and molecular machinery-the hardwarecomplicated and difficult to debug. The researchers'
what to do. But instead of electronic circuitry, life
new approach, however, involves components that
relies on biochemical circuitry-complex networks of are simple, standardized, reliable, and scalable,
reactions and pathways that enable organisms to meaning that even bigger and more complex
function. Now, researchers at the California
circuits can be made and still work reliably.
Institute of Technology (Caltech) have built the
most complex biochemical circuit ever created
"You can imagine that in the computer industry, you
from scratch, made with DNA-based devices in a
want to make better and better computers," Qian
test tube that are analogous to the electronic
says. "This is our effort to do the same. We want to
transistors on a computer chip.
make better and better biochemical circuits that can
do more sophisticated tasks, driving molecular
Engineering these circuits allows researchers to
devices to act on their environment."
explore the principles of information processing in
biological systems, and to design biochemical
To build their circuits, the researchers used pieces
pathways with decision-making capabilities. Such of DNA to make so-called logic gates-devices that
A wiring diagram specifying a system of 74 DNA
molecules that constitute the largest synthetic circuit of
its type ever made. The circuit computes the square root
of a number up to 15 and rounds down to the nearest
integer (the discrete square root of a four-bit integer).
Credit: Caltech/Lulu Qian
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produce on-off output signals in response to on-off any number up to 15 (technically speaking, any fourinput signals. Logic gates are the building blocks of bit binary number) and round down the answer to
the digital logic circuits that allow a computer to
the nearest integer. The researchers then monitor
perform the right actions at the right time. In a
the concentrations of output molecules during the
conventional computer, logic gates are made with calculations to determine the answer. The
electronic transistors, which are wired together to calculation takes about 10 hours, so it won't replace
form circuits on a silicon chip. Biochemical circuits, your laptop anytime soon. But the purpose of these
however, consist of molecules floating in a test tube circuits isn't to compete with electronics; it's to give
of salt water. Instead of depending on electrons
scientists logical control over biochemical
flowing in and out of transistors, DNA-based logic processes.
gates receive and produce molecules as signals.
The molecular signals travel from one specific gate Their circuits have several novel features, Qian
to another, connecting the circuit as if they were
says. Because reactions are never perfect-the
wires.
molecules don't always bind properly, for instancethere's inherent noise in the system. This means
Winfree and his colleagues first built such a
the molecular signals are never entirely on or off,
biochemical circuit in 2006. In this work, DNA signal as would be the case for ideal binary logic. But the
molecules connected several DNA logic gates to
new logic gates are able to handle this noise by
each other, forming what's called a multilayered
suppressing and amplifying signals-for example,
circuit. But this earlier circuit consisted of only 12
boosting a signal that's at 80 percent, or inhibiting
different DNA molecules, and the circuit slowed
one that's at 10 percent, resulting in signals that are
down by a few orders of magnitude when expanded either close to 100 percent present or nonexistent.
from a single logic gate to a five-layered circuit. In
their new design, Qian and Winfree have
All the logic gates have identical structures with
engineered logic gates that are simpler and more different sequences. As a result, they can be
reliable, allowing them to make circuits at least five standardized, so that the same types of
times larger.
components can be wired together to make any
circuit you want. What's more, Qian says, you don't
Their new logic gates are made from pieces of
have to know anything about the molecular
either short, single-stranded DNA or partially
machinery behind the circuit to make one. If you
double-stranded DNA in which single strands stick want a circuit that, say, automatically diagnoses a
out like tails from the DNA's double helix. The
disease, you just submit an abstract representation
single-stranded DNA molecules act as input and
of the logic functions in your design to a compiler
output signals that interact with the partially double- that the researchers provide online, which will then
stranded ones.
translate the design into the DNA components
needed to build the circuit. In the future, an outside
"The molecules are just floating around in solution, manufacturer can then make those parts and give
bumping into each other from time to time," Winfree you the circuit, ready to go.
explains. "Occasionally, an incoming strand with
the right DNA sequence will zip itself up to one
The circuit components are also tunable. By
strand while simultaneously unzipping another,
adjusting the concentrations of the types of DNA,
releasing it into solution and allowing it to react with the researchers can change the functions of the
yet another strand." Because the researchers can logic gates. The circuits are versatile, featuring plugencode whatever DNA sequence they want, they
and-play components that can be easily
have full control over this process. "You have this reconfigured to rewire the circuit. The simplicity of
programmable interaction," he says.
the logic gates also allows for more efficient
techniques that synthesize them in parallel.
Qian and Winfree made several circuits with their
approach, but the largest-containing 74 different
"Like Moore's Law for silicon electronics, which
DNA molecules-can compute the square root of
says that computers are growing exponentially
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smaller and more powerful every year, molecular
systems developed with DNA nanotechnology have
been doubling in size roughly every three years,"
Winfree says. Qian adds, "The dream is that
synthetic biochemical circuits will one day achieve
complexities comparable to life itself."
More information: Science paper: "Scaling up
digital circuit computation with DNA strand
displacement cascades"
Provided by California Institute of Technology
APA citation: Largest biochemical circuit built out of small synthetic DNA molecules (2011, June 2)
retrieved 18 June 2017 from https://phys.org/news/2011-06-largest-biochemical-circuit-built-small.html
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