In a step toward sophisticated artificial cells, scientists have engineered a silicon chip that can produce proteins from DNA, the most basic function of life.
The system, though relatively simple, suggests a path to mimicking life with partly manufactured components, says Roy Bar-Ziv, a materials scientist at the Weizmann Institute of Science in Israel, who is leading the work.
Cells constantly create proteins from instructions coded in DNA sequences. How much of each protein is made is controlled by other genes, often in complicated feedback loops. Bar-Ziv calls his cell-on-a-chip “a new system allowing us to examine how genes are turned on and off outside the living cell.”
The chips were created using a technique Bar-Ziv’s lab developed several years ago to anchor DNA to silicon by first coating the surface with a light-activated chemical. They used patterns of light to create spots where DNA binds and assembles into toothbrush-like bundles. Each DNA brush was confined to a small, round compartment. These compartments were joined by a narrow capillary 20 micrometers wide to a larger channel, which carried a flow of liquid extracts from bacterial cells—all the ingredients needed to synthesize proteins from the DNA brushes.
The system, described in a Science paper in August by Bar-Ziv, along with his students Eyal Karzbrun and Alexandra Tayar, and Vincent Noireaux of the University of Minnesota, allowed the researchers to create a simple network of interacting genes.
Scientists can already easily synthesize proteins from DNA in a test tube, but those reactions eventually fizzle out as proteins accumulate and synthesis slows. That has made it hard to create functioning genetic circuits—interacting networks of genes and proteins—outside of cells. Bar-Ziv says his chip overcomes that problem by flushing away waste products. Also, by changing the lengths of the channels leading to each DNA compartment, he was able to control how fast the proteins manufactured in it diffused to other areas of the chip, influencing other reactions. “If you want to reconstitute the dynamic nature of genes going up and down, you have to have a mechanism for degrading what you make,” says Bar-Ziv.
Other synthetic biologists—so-called because they seek to create novel, engineered genetic circuits—have also begun installing their DNA programs outside of living things, such as on sheets of paper, with an eye to creating new kinds of diagnostic tests (see “Synthetic Biologists Create Paper-Based Diagnostic for Ebola”).
Similarly, Bar-Ziv’s chip may eventually lead to applications in diagnostics, environmental sensing, or drug screening, with the twist that it could keep reactions going for a longer time. Scientists say the chips could be used to test new genetic constructs before they’re put into actual cells, like bacteria. “If I can rapidly prototype these designs outside of cells and then just select the best few to put into cells, it could speed up the process,” says Timothy Lu, a synthetic biologist at MIT.
The next step, says Bar-Ziv, is to create more complex patterns and larger networks. He hopes to eventually be able to control hundreds of different genes in thousands of artificial cells at once, allowing them to communicate with and influence one another, not unlike in a living organism. That’s still a ways off, he admits. “Going from one transistor to billions didn’t happen in a day,” he says.
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