University of Delaware
Prof. James Collins of MIT (center) chats during a reception before his lecture. With him are (from left) Andrew Jefferson, son of the late Edward G. Jefferson (for whom the lecture is named), Provost Domenico Grasso, Charles Riordan, deputy provost for research and scholarship , and Klaus Theopold, professor of chemistry and biochemistry.

Harnessing power of genetic circuitry

Synthetic biology pioneer explains advances that could address significant health problems

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10:46 a.m., May 9, 2016--If researchers anywhere needed a booster shot of inspiration, the University of Delaware's Edward G. Jefferson Lecture was a great place to be Tuesday, May 3, as pioneering biological engineer James Collins sketched out some of the paths he and his collaborators are pursuing in a lecture he called "Redesigning Life."

That idea – redesigning life – might strike a bit of fear into many mere mortals, who wonder what scientists might unleash on humanity if they tinker with enzymes or mess around with recombinant DNA.

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And that's the kind of thing Collins, a longtime professor at Boston University and now the Termeer Professor of Medical Engineering and Science at MIT, and his collaborators do. They are working to use the tools of molecular biology to manipulate cellular processes and carry out specific missions that don't happen in natural genetic circuitry.

He acknowledged and addressed the worry some might have when they hear of such work, using part of his lecture to describe controls that limit processes and reactions by time or function, including such things as "kill switches" for microbes. Certain molecules must be present for things to work.

"Then they commit cellular hara-kiri," he said.

Collins has been at the forefront of design and construction of synthetic gene-regulatory networks for years, developing methods and plans that make such circuitry seem akin to electronics, a fuse box or a valve where you can turn things on or off at will.

It has been more than 15 years since his Nature article that described construction of a stable genetic toggle switch. Biologists had listened to the idea, he said, but most said "no way" until his colleague at Boston University, Charles Cantor, said "maybe" and opened the door of his lab.

Now the possibilities for such work seem to be expanding in many directions and Collins and dozens of collaborators continue to explore ideas that could turn the tide in diagnosing and treating disease and dealing with significant challenges such as antibiotic-resistant infections.

For example, Collins said, could we engineer a "bug" that detects bowel inflammation without need for an endoscopy? Could you engineer something that detects and treats cholera, MRSA, the Zika virus, lung infections? Could we make a bacteriophage (a virus that goes after bacteria) to boost the effectiveness of antibiotics?

One of his companies, Synlogic, with "Powering the Microbiome" as its slogan, is working to develop probiotic drugs that would disrupt and correct disease-causing problems, stop when its mission is accomplished and then self-destruct.

He envisions a day when you could pull out a kit, equipped with  portable molecular manufacturing materials, and make what you need when you need it – vaccine antigens, therapeutic proteins and such.

Collins' work has been recognized by every major scientific cadre of excellence – the National Academies of Sciences, Engineering and Medicine, as well as the National Academy of Inventors – a list of honors that Charles Riordan, UD deputy provost of research and scholarship, likened to winning all of the entertainment industry's major awards – the Emmy, Grammy, Oscar, Tony and Indie.

"He has the ability to identify important problems and bring scientific and engineering solutions to those problems," Riordan said. "Innovation is in his DNA."

The Edward G. Jefferson Lecture, endowed by a gift from the Unidel Foundation, is named in honor of the late chairman and chief executive officer of DuPont, UD trustee emeritus and UD benefactor. His son, Andrew, president and CEO of the 6Ds Company, was present for the lecture.

Article by Beth Miller

Photos by Lane McLaughlin and David Barczak

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