DNA computer readout glows

By Kimberly Patch, Technology Research News

DNA is the ultimate biological code, packing all the information needed to make life forms as diverse as viruses, turnips and human beings into a microscopic package that can copy itself and automatically carry its own instructions.

It's no wonder that biologists and computer scientists are working toward using DNA for computing. Computers that use the microscopic molecules have the potential to solve certain types of very large problems, like finding the most efficient traveling salesman route or circuit board layout, much faster than conventional computers. This is because many DNA molecules can be used to work on all possible solutions to a problem at once.

Researchers from the University of Wisconsin-Madison have come up with a better way to read the results of a microscopic DNA computation once it is completed.

The challenge to reading DNA computing results is the molecules that represent the answer to a problem are mixed in with other DNA molecules, and it is difficult to pick out the right ones. The researchers' method makes the right molecules stand out by giving them the microscopic equivalent of the glow sticks people wave around at large outdoor events.

The approach "is a different way of finding out what is there," said Lloyd Smith, a chemistry professor at the University of Wisconsin-Madison and a director of Third Wave Technologies, Inc.

DNA molecules are made up of long strings of four types of bases connected to phosphate backbones. The order of the bases makes up a type of code.

DNA computers consist of large sets of DNA molecules that include all possible answers to a computational problem. During the DNA computing process a series of enzymes takes the DNA molecules through the logical steps needed to compute the correct answer by combining them and breaking them in different places to form new sequences. At the end of the computation there is a small subset of DNA molecules that represent the correct solutions to the problem.

The researchers' readout method involves putting the DNA into a series of wells that contain an enzyme and other DNA strands that contain inactivated fluorescent molecules. The combination lights up the correct answers by a method known as invasive cleavage. The DNA molecule representing the answer causes the enzyme to cleave, or cut, the fluorescent molecule free from its DNA strand, causing it to glow. "If a certain DNA molecule is present... the cleavage makes fluorescence appear," said Smith.

The cleavage method already existed, but it took some work to adapt it for reading DNA computing answers, said Liman Wang, part of the University of Wisconsin-Madison team, and now a senior research chemist at Merck Co. Inc. The researchers had to delete certain portions of the DNA in order to produce the specific sequence needed for the invasive cleavage method, said Wang.

The method is simpler and more accurate than previous readout methods, said Wang. "The signal uniformity has been significantly improved, and false positive signals are much less -- in other words, the signal-to-noise ratio is higher."

The method is "an experimental improvement on the way Smith and his colleagues have been performing DNA-based computation for a number of years," said Nadrian Seeman, a chemistry professor at New York University. "They have increased the fidelity of their readout method," he said.

The key issue is whether the general method will work with very large problems, said Seeman. "The issues involve both the difficulty of setting up the problem and the accuracy of the results. These authors have improved the accuracy of the results," he said.

The researchers are working to make fluorescence reaction uniform among all the different DNA answers, said Wang.

DNA computing is at least 10 years away from being used in practical applications, said Smith.

Smith and Wang's research colleagues were Jeff Hall of Third Wave Technologies, and Manchun Lu and Qinghua Lu of the University of Wisconsin-Madison. They published the research in the November, 2001 issue of Nature Biotechnology. The research was funded by the National Science Foundation (NSF) and the Defense Advanced Research Projects Agency (DARPA).

Timeline:   Now, > 10 years
Funding:   Government
TRN Categories:  Biological, Chemical, DNA and Molecular Computing
Story Type:   News
Related Elements:  Technical paper, "A DNA Computing Readout Operation Based on Structure-Specific Cleavage," Nature Biotechnology, November, 2001.


January 30, 2002

Page One

Crystal stores light pulse

Rocket chips to propel small satellites

Computers sort gender in a binary world

Quantum network withstands noise

DNA computer readout glows


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