and methodologies so members of a
team understand each other. “What a
protocol means to computer scientists
is communication procedures, while it
means to biologists experimental procedures,” says Tadashi Nakano, a professor
of computer science at the University of
California, Irvine (UCI). “This is a trivial
example, but in order to communicate
with biologists, I first needed to learn
a set of vocabularies that they use in
daily conversation; and I needed to explain computer science vocabularies to
them.” Nakano’s research in the Molecular Communication Group at UCI
in-volves cell biology, nanotechnology,
and communications engineering,
with the ultimate goal of the work being to integrate these disciplines and
establish molecular communication
as a science.
Currently, Nakano and colleagues
are focused on engineering cell-to-cell
communication through calcium signaling. The photograph on page 11
shows a series of images captured as
a mechanically induced calcium wave
propagates through several cells. To
monitor the waves, Nakano’s team
loaded cells with calcium-sensitive fluorescent dyes, then used a micropipette
to mechanically stimulate a cell and a
fluorescence microscope to capture the
images. Nakano says the project, which
is in an early stage, is focused on designing the key components, such as amplifiers and switches, that are necessary to
build a cell-based network. To realize
some of the promises of molecular communication, says Nakano, the field’s
understanding of cellular communication must be expanded and engineering techniques for modifying cell functions must be advanced. “Our current
attempt is like designing systems using
black boxes or components whose behavior is not completely predictable,”
he says. “Our hope here is being able to
reveal what’s inside the black boxes—
that is, answering unknown questions
in cell biology.”
Dna Walkers
Most molecular communication projects—such as Nakano’s work and projects under way at other research labs
around the world—share a focus on
sender nanomachines, receiver nanomachines, carrier molecules, and the
environment in which these tiny objects
a Dna walker created by caltech chemists
Jong-shik shin and niles a. Pierce. the
vertical strands form the walker’s body and
legs, which walks on the horizontal track.
operate. Senders and receivers include
biological and biologically derived nanomachines that are capable of emitting
and capturing carrier molecules, such
as proteins, ions, or even DNA. Several
research teams, for example, have built
DNA walkers that operate much like ki-nesins, which are motor proteins that
use ATP hydrolysis to move along micro-tubules. The goal of these projects is to
construct a synthetic transport device
that mimics the linear movement of motor proteins and can be used not only to
carry a signal but also to carry out nanoscale computations.
Niles Pierce, a Caltech professor of applied and computational mathematics
and bioengineering, and his colleagues
have created a walker that can move
along a DNA track. The first DNA walker
that Pierce created several years ago was
not autonomous—it required external
control over the fuel strands—but his
colleagues and him have built on the initial work and have created a microscale
system that powers itself. “The key innovation in moving from nonautonomous
to autonomous motors (both powered
by the formation of DNA base pairs) was
to develop conformation-changing molecules that could bind to one molecule
and then change structure to deliver energy to the system,” says Pierce.
Currently, Pierce and his colleagues
are working on the algorithms needed
to create what he calls “a compiler for
molecular computing” that will take
as input a high-level abstraction of the
desired function for a molecular system and produce as output molecular
sequences that can be synthesized to execute the function in a test tube or cell.
Pierce is also working to develop both
nanomechanical instruments that use
molecules to detect and regulate signals in living cells and nanomechanical drugs designed to kill diseased cells
while leaving healthy cells untouched.
“It is a huge scientific challenge to model the cellular environment in which
our synthetic molecular systems must
operate in living systems,” he says. “It
remains to be seen how significant the
resulting uncertainties are in thwarting
our engineering efforts.”
At present, molecular programming
is a research topic, and Pierce says science is far from creating general solutions to these design challenges. Pierce
estimates that it will take a minimum
of three to five years to achieve practical
nanomechanical instrumentation and
10 to 15 years before there are nanomechanical drugs. “But there are already
some systems,” he says, citing Caltech
researcher Paul Rothemund’s “DNA origami” method for constructing shapes
and patterns, “where high school students can program molecules using a
simple CAD interface to specify nanoscale details of the self-assembling
structures.” Other notable research includes John Reif’s work at Duke University, which is focused on self-assembling
nanostructures; Tom Knight’s work at
MIT, which is oriented toward standardizing DNA components for synthetic
biology; and the work of Caltech’s Erik
an example of caltech researcher Paul
Rothemund’s “Dna origami” method for
constructing shapes and patterns.