The promise of this new field was explored during a state-of-the-art plenary lecture Sunday morning at AUA2017.
“This exciting new field of synthetic biology is already beginning to impact diagnostics and could soon have an impact in urology,” said James Collins, PhD, the Termeer Professor of Medical Engineering and Science and professor of Biological Engineering at the Massachusetts Institute of Technology, and Core Founding Faculty Member of the Wyss Institute for Biologically Inspired Engineering at Harvard University. “We helped launch the field in the late 1990s when we recognized that an engineer could design a circuit and model it mathematically, and then we, with biologists, could come up with the notion of a biological circuit — so, not a dry one, but a wet one.”
Dr. Collins’ research group works in synthetic biology and systems biology, with a special focus on using network biology approaches to study antibiotic action, bacterial defense mechanisms and the emergence of resistance.
“Just as an engineer would try to find resistors, capacitors or inductors and solder them as a circuit, we recognized that one could go find gene promoters, terminators, enhancers and other bits of DNA/RNA proteins and use the tools of recombinant DNA to create wet circuits, and that you could then program cells to do interesting things,” Dr. Collins said. “We and others in the last few years have shown that you can use these circuits to rewire living organisms to serve as living diagnostics and living therapeutics. We’ve shown, for example, that you can take a lactate bacterium that you find in yogurt and cheese and rewire it to detect and treat different infections or inflammation.”
That discovery led Dr. Collins and others to ponder the possibilities and implications of moving synthetic biology out of the lab and into clinics.
“We became engaged in the possibility of how you could take advantage of the power and diversity of biology without using a living cell and we recognized, a little over two years ago, that you could harness cell-free extracts,” he explained. “Basically, that involves opening up a living cell and taking out its inner machine, which would typically consist of a few dozen enzymes and molecular machines such as ribosomes.”
Subsequently, one of Dr. Collins’ colleagues wondered what would happen if that cell-free extract were freeze-dried.
“He wanted to know if that extract would lose activity if it was spotted on paper and then freeze-dried. Somewhat surprisingly, the answer was no,” Dr. Collins said. “He found that he could freeze cell-free extracts on paper, rehydrate it sometime later, and what he had spotted on paper would actually function as if it were inside a living cell.”
More recent research has found that the system is not limited to paper and works on any porous medium, including plastic, glass and cloth.
“Further, we’ve found that it doesn’t need a substrate,” Dr. Collins said. “This system can be freeze-dried as pellets and, in work we published a few months ago, we showed that you can now have a small plastic kit of freeze-dried, cell-free pellets or freeze-dried, engineered DNA pellets that you can use in the field to produce biomolecules of interest. The notion here is that health care workers in developing countries, or military personnel or Matt Damon on Mars could now have this small kit that can be used to make what’s needed on an on-demand basis.”