How to Build a Living Machine

A molecular biologist gives a common organism a remarkable skill using man-made genes

How to Build a Living Machine
University of California, San Francisco researcher Jeff Tabor has programmed bacteria to print a self portrait. [Credit: Jeff Tabor, UCSF]
By | Posted January 27, 2010
Posted in: Life Science
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Jeff Tabor has invented a living camera.

It’s a tiny creature. A modified bacterium, really. A modest thing, Tabor admits, compared to the kinds of life forms scientists talk about some day being able to make, like, say, diesel-manufacturing cows.

But Tabor’s organism is one of the most sophisticated genetic engineering projects scientists currently know how to execute using artificial biological parts. And Tabor, who published his work in June 2009 in the journal Cell, is continuously adding to its complexity. His organism is a small but important feat for synthetic biology — a young field with huge goals and decades of research to go in order to reach them.

Plus, Tabor’s organism can do something extraordinary, something no natural living thing can do. Tabor’s organism can print pictures.

“It was a completely outlandish idea when we came up with it,” said Tabor, a post-doctoral fellow at the University of California, San Francisco.

Five years ago, when Tabor and his colleagues at the University of Texas, Austin first dreamed up the organism for an annual genetic engineering competition sponsored by the Massachusetts Institute of Technology, they never expected it would work. “We knew we could engineer living cells with genes and gene parts, but nothing remotely close to this had been done before,” he said.

Researchers have been constructing synthetic biological parts for less than ten years. By stitching together basic chemicals, they can build fragments of DNA and the genetic structures that control its expression.

Recently, scientists like Tabor have begun assembling these components in configurations that don’t exist in the natural world and inserting them into bacterial cells. Sometimes, though far less often than these scientists would like, the cells read the new genetic instructions and acquire new behaviors according to the code. In this way, scientists have engineered organisms that perform novel tasks, like manufacturing anti-malarial drugs, counting, and arranging themselves in patterns.

But designing these genetic programs and running them in living cells isn’t easy.

“It’s really hard to get them to work in the way you like. It takes months, if not years, of tweaking,” said Jim Collins, a molecular biologist at Boston University who built some of the first synthetic gene structures. “They typically fail.”

But Tabor got lucky.

One day in the spring of 2007, he slipped a petri dish coated with genetically beefed-up bacteria under a Kodak slide projector and waited. The image he projected was simple — just a disk of red light on a dark background.

Tabor already knew how to engineer the bacteria to display a basic black-and-white photograph-like reproduction of any image — a profile of Charles Darwin, for example, or the words “hello world.” By injecting the cells with artificial DNA sequences, he’d programmed them to sense red light. If they detected no light at all, the bacteria would manufacture a black pigment. So when Tabor projected an image onto a dish of bacteria, the lighted regions stayed light while the dark regions turned dark. An exact picture replica.

But this time, he wanted them to do something much more difficult. He wanted them to trace only the edge of the disk he projected.

This required a more complex gene system, which Tabor designed to work like a logic puzzle. The puzzle goes like this: say you’re a bacterium in Tabor’s petri dish, and Tabor has given you several abilities and a set of rules for how to use them.

Here are your abilities: You can sense red light, send chemical messages to your immediate neighbors, receive chemical messages, and manufacture black pigment.

Here are the rules: you can send messages if and only if you don’t detect light; you can receive messages if and only if you do detect light; and you can make pigment if and only if you receive a message. The puzzle works out such that you can turn yourself black only if you exist on the very edge of a light beam.

In other words, Tabor was telling his bacteria to draw a circle.

He had tried to instruct them dozens of times, each time using a slightly different configuration of chemical base pairs, the building blocks of DNA. In the end, he constructed a sequence of over 10,000 such pairs — a sequence that, if it were an army of ants marching antenna to stinger, would span a city block.

“Engineers within the field of synthetic biology are ultimately trying to create systems that are 400 to 200,000 times more complicated,” said Drew Endy, a synthetic biologist at Stanford University. According to Endy, constructing an entire bacterium from scratch would take about eight million base pairs — an ant line stretching from Baltimore to Washington, D.C. If you wanted to build something as complex as a mouse or a human, you’d need a sequence as long as four billion base pairs, or enough ants to march across the United States.

But Tabor was dealing with DNA of a more manageable size. And so, as his bacteria multiplied under the red light, they began to behave exactly as he’d programmed them.

When he pulled out the slide 12 hours later, he remembers, “there was this beautiful ring exactly as I’d imagined it.”

Tabor says he’s now working on engineering bacteria that can print pictures in color. He’s not trying to advance photography, but instead to enable the construction of more complex living systems — like artificial tissues or organisms that detect toxins in the environment.

Tabor predicts that if he and other synthetic biologists keep getting lucky, then maybe — just maybe — they will be able to engineer life “on the scale of building a mouse, like the whole thing,” during his lifetime. “Presumably the sky is the limit,” he said.

Posted in: Life Science

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    holp, August 16, 2010 at 6:58 am
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