Turning biologists into programmers

For more than half a century scientists have looked on the DNA molecule as life's blueprint. Now biological engineers are beginning to see the molecule not as a static plan, but more like a snippet of life's computer code that they can program.

Penn State researchers are unraveling the mystery of how nature codes and recodes this program to address some of the world's biggest challenges, says Howard Salis, assistant professor of biological engineering and chemical engineering.

"You can engineer DNA to reprogram the metabolism of simple organisms and you can program them to make what you want, or to make it more efficiently, says Salis. "The trick is to understand how the organism interprets its DNA, and then to optimize new DNA sequences to rationally control its behavior."

This rapidly developing field, often referred to as synthetic biology, may one day allow biological engineers to design living systems just as reliably as engineers currently design and build airplanes, cars and trains, according to Salis. It also holds the key to products such as inexpensive biofuels, environmentally friendly plastics, and less expensive pharmaceuticals.

"Decoding the function of DNA -- what the DNA makes the organism do -- and then recoding it with a new human-desired function is central to synthetic biology," he says.

Adenine, cytosine, guanine and thymine are the chemical components of DNA. Better known by their initials, ACGT, these chemicals form the nucleotide bases of DNA and combine in a mind-boggling arrangement to specify which amino acids are needed to make certain proteins.

Biological engineers are starting to sound more like computer engineers as they begin to also look at DNA as information -- something that can be decoded and recoded -- as well as its blend of chemicals.

Salis’s group recently developed a genetic compiler software that researchers and scientists have used to predict and help control protein expressions in bacteria. So far, it has designed more than 30,000 sequences for academic and commercial researchers around the globe. The software cuts down on time-consuming trial and error and is a significant step toward unlocking biology as an advanced manufacturing platform, Salis says.

Despite the futuristic sound of synthetic biology, the idea -- and simple forms of the technology -- have been around for decades, he adds. One example of this early use of biological engineering is the use of fungi to manufacture penicillin, one of the most common forms of antibiotics -- a technique discovered in 1928. In the late 1970s, researchers used genetic engineering techniques to produce synthetic insulin that could be used to treat diabetic patients. The discovery helped replace insulin derived from pigs, which was expensive and often ineffective.

In the 2000s, better and faster computers have steadily boosted DNA sequencing and synthesis technologies, enabling the sequencing of the human genome and the synthesis of whole bacterial genomes.

Salis sees the early achievements of synthetic biology as only the beginning of ways researchers will improve upon nature's evolutionary genius.

"Evolution was the first engineer and now we are learning how to take evolution into different directions to solve humanity's problems," he says. "Since all life uses DNA, it's the same genetic code, just interpreted in different ways."

A host of applications

He and other biological engineers are busy discovering ways to turn leftover agricultural products into sustainable biofuels that can ease fuel costs and help boost energy independence. By tweaking the DNA, engineers have developed microbes that digest corn leaves and stalks, produce sugars and then convert the sugars into biofuels. Their goal is to fine-tune the microbe's genetic code to optimize biofuel production and deliver a superior, low-cost product.

"We could redesign bacterial metabolism to make it a super biofuel producer," he says.

Significant hurdles remain to make the process economical. As Salis explains, funding for biofuel projects usually traces the path of gasoline prices. As those prices increase and consumers chafe under higher costs, biofuels become more acceptable and economical, which attracts investors and venture capitalists. However, when consumers adjust to higher fuel prices, interest in finding alternative sources of energy wanes.

"The cyclical nature of research funding has greatly harmed our ability to overcome technical and economical hurdles," says Salis. "You need a long-term commitment to the project."

In addition to helping quench the world's growing demand for energy, biological engineers may use synthetic biology techniques for medicine. Salis says engineers can reprogram organisms' metabolisms to produce anti-cancer and anti-bacterial drugs.

Living organisms can be reengineered to do more than build things -- they can also be used to break things down and clean them up, he adds. Bacterial metabolisms could be programmed to digest industrial waste material and toxic chemicals, for example.

However, Salis recognizes that talk of genetically engineered microbes worries some people.

"We have been domesticating bacteria and yeast to make bread, beer and yogurt for thousands of years," he says. "When we engineer microbes to make a new drug or a new fuel, the microbe does not survive very well in the outside world."

Competition between all microbes -- natural and engineered -- will put the brakes on any microbe that tries to do one thing very well, he adds.

"One thing we do as engineers is learn how to, from a critical point of view, balance what risks to take compared to the benefits of taking those actions," he says.

In fact, his team is working on building a genetic security system to prevent genetically modified DNA from falling into the wrong hands. Engineering DNA to perfection still takes a long time and industrial espionage in biotechnology is a growing problem.

"DNA is the ultimate self-replication information storage device," says Salis. "Once you build a better DNA molecule, that's your product."


Howard Salis is assistant professor of agricultural and biological engineering, hms17@psu.edu.

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Last Updated October 17, 2013