Microbe computers - Built from the stuff of life by ANDREW MYERS Bacteroides thetaiotaomicron is one of the good guys. Known simply as Bt, it is an abundant member of the estimated 500 to 1,000 species of bacteria that live in the human intestine and one of the lead players in a remarkable symbiosis between man and microbe. Bt does what our bodies can’t. It ingests complex sugars and breaks them down into usable nutrients that can then be absorbed by our digestive system. We may be stardust, but we are also microbe excrement. Inflammatory bowel disease, in contrast, is about as unpleasant as the name implies. The complex condition has baffled science for decades. Among its peculiarities is the fact that the bacteria in the guts of sufferers vary significantly in type and number from those of healthy humans, Bt chief among them. “Unfortunately, we don’t know whether these variations in the bacterial populations are a root cause or a resulting symptom of inflammatory bowel disease, and, until recently, we were very limited in the tools available to answer that question,” says Justin Sonnenburg, PhD, a Stanford assistant professor of microbiology and immunology who studies relationships between gut microbes and health. He’s in the vanguard of scientists applying a new research tool that provides unprecedented control of microbes. That tool is a computer, but not a computer made of silicon, metal and plastic. It’s a computer made of DNA, RNA and enzymes, residing within the confines of a single cell. THE BUILD This biological microcomputer sprang from the mind of Drew Endy, PhD, an assistant professor of bioengineering at Stanford. In three scientific papers released over a 13-month span in 2012 and 2013, Endy and a team of researchers from his lab showed how they used ordinary genetic engineering techniques to turn the bacterium E. coli — that stalwart of the Petri dish — into a machine capable of the basic functions of a computer: logic, data storage and data transmission. They also showed that their techniques will work in any type of living cell, not just bacteria. And while others have accomplished similar feats, Endy’s system has the singular advantage of being able to amplify the information flow. “Amplification is what makes this system the best,” says Endy. “It’s the equivalent of the transistor in an electronic device. It’s what makes our computer really useful.” So it’s a cool bit of engineering, but it’s more than that. The work “… clearly demonstrates the power of synthetic biology and could revolutionize how we compute in the future,” said fellow biological engineer Jay Keasling, PhD, at the University of California-Berkeley, quoted in the San Jose Mercury News. Other researchers echoed this opinion, as did the Journal of Biological Engineering, which recognized one of the three articles — “Engineered cell-cell communication via DNA messaging” — as its Publication of the Year. Speed-wise at least, IBM won’t feel threatened by the biocomputer. “The microbial processor operates in the millihertz time frame — about one cycle every 1,000 seconds, or about four times per hour,” Endy says, “But in biology it doesn’t always matter; slow can be beautiful.” The biological computer opens up a host of research avenues never before imagined, much less pursued. Microbes could be engineered to detect cancer, for instance, and then tag malignant cells with fluorescent markers for easy identification. Other cells might be programmed to detect those markers and deliver with pinpoint accuracy pharmaceuticals they themselves manufacture on the spot, much as Bt produces and excretes nutrients. Biological computers might even someday be able to reprogram cancer cells to shut off their own growth. Unfortunately, at first biologists often have a hard time understanding his work, Endy says. “When I talk about this to groups of biologists, the initial response is usually, ‘Harrumph. That’s not how biology does it,’” he says. “They’re not used to thinking like engineers.” Once he explains that he’s using biology to build something simpler and easy to control, something useful, they begin to warm up to the idea. Endy knows of several scientists starting projects using his system and he hopes many more will take it up. An advocate of open-source technology (which, as with open-source software, makes its discoveries and technologies free to the public), he has made the instructions available free online. A video primer is also on YouTube (stan.md/15u6OtC); it’s been viewed nearly 30,000 times. ..... stanford.io/1dOh6Ht
Posted on: Wed, 06 Nov 2013 21:06:16 +0000
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