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.