[tt] newscientist: DNA compiler/design helper (?) and two-legged walking DNA molecule

[Alejandro Dubrovsky]

(
hard to tell from the text what kind of program  (what inputs and
outputs) this is
http://technology.newscientist.com/channel/tech/dn13192-dna-fabricator-constructs-walking-dna.html?feedId=online-news_rss20
)

DNA 'fabricator' constructs walking DNA

 * 18:00 16 January 2008
 * NewScientist.com news service
 * Robert Adler

The goal of being able to program biochemical reactions as precisely and
easily as computers crunch numbers and process words has moved a giant
step closer.

A group at the California Institute of Technology, led by biomolecular
engineer Niles Pierce, has created a DNA-based fabricator.

This is a system that allows the team to specify a piece of DNA with a
desired shape and function, and then execute a molecular program to
assemble it in a test tube. As an example, they used their system to
construct a piece of DNA that walks along another strip of.

Just as computer languages let programmers create any number of
applications, the researchers behind the approach predict that
biochemical programming "languages" inspired by their work could let
bioengineers create any number of desired molecular products and
processes.

Other researchers have created a variety of DNA-based objects, including
self-replicating nanostructures, movable arms, tweezers, nanoscale
faces, maps and other structures, and even game-playing computers.

But Pierce and his group have gone even further with their biochemical
programming.
Bespoke reactions

"We have shown that you can actually program the interactions between
these molecules to implement different dynamic functions using the same
components," says Pierce.

At the heart of the group's system are hairpin-shaped strands of DNA
each about 10 nanometers long with three specific binding sites called
"toeholds".

These hairpins can snap together in specific ways. When a hairpin is
closed, for example, two out of its three binding sites are unavailable.
But, if a suitable strand of DNA docks with it, the hairpin springs
open.

A reaction between two DNA strands can also free up the exposed site on
an attached hairpin, causing it to close once more.

In computer terms, the hairpins act as interconnected logic gates. "This
elementary unit has one input port and two output ports," says Pierce.
"And they can interact – the input port of one can receive an input from
the output port of another."
Practical tasks

The group has also developed a graphical way to represent the state of
these molecular building blocks and the step-by-step interactions
between them. These "reaction graphs" allow them to map out the assembly
and disassembly steps needed to produce a desired sequence of reactions.

The necessary reactions are then translated into specific sequences of
complementary DNA base pairs with the requisite binding characteristics.
Finally, the program runs in a test tube that contains the specified mix
of molecules.

To demonstrate the power and flexibility of their programming approach,
the group used it to produce several different reactions including, most
dramatically, two-legged DNA molecules that walk along a ladder-like
track.

Pierce's group also demonstrated other reactions that could be useful
for practical tasks, such as biosensing.
Engineering challenge

The two-legged walker, says Pierce, was inspired by the vital
intracellular transport protein, kinesin, which walks along microtubules
at about 100 steps per second.

"It remains a phenomenal engineering challenge to attempt to encode that
functionality from scratch," he says.

Pierce admits, however, that the group has taken just the first few
steps towards programming biological structures and functions at will.

Still, he says, a few years ago audience members laughed when he said he
wanted to create a compiler to automate the process of encoding desired
functions into DNA sequences. "Our field has now progressed to the point
where the real question is not whether it can be done, but how far it
can be pushed."

Some of Pierce's peers believe this kind of systematic biomolecular
programming can be pushed very far indeed.

"It's great work," says computer scientist Erik Winfree, who is also at
based Caltech, but was not involved with the work. "What's remarkable is
that it develops a general way of creating a very diverse set of
chemical reaction pathways. It opens a lot of doors."

Journal Reference: Nature (vol 451, p 320)