“Life finds a way.”
Jeff Goldblum’s character Dr. Ian Malcolm utters these infamous words at the beginning of 1993’s Jurassic Park, eerily foreshadowing the eventual chaos. Malcolm is arguing against the park’s scientists’ insistence that the movie’s dinos cannot procreate on their own – asserting that the power of evolution is more inventive than man could anticipate.
Ultimately, Goldblum’s character is referring indirectly to trees that sprout in the middle of sidewalks, lizards that can run on water and birds that swim. Evolution produces diverse solutions to complex challenges in all environments across the earth; it is an unrivaled problem-solving tool. Researchers at Harvard University recently refined a technique that uses applied evolutionary science as a tool to build custom proteins.
Proteins are a diverse class of molecules with limitless applications. In the human body, proteins digest food, move limbs, protect health, transcribe and copy genetic information and even build other proteins. In industrial applications, proteins produce biofuels, dissolve stains in clothing and contribute to the flavors of yogurt, cheese, wine, beer and many other foods. The capacity to design custom proteins with new and specific functions has the potential to forever alter the landscape of medicine and industry.
University of Wyoming molecular biology professor Dr. David Liberles said there are two general strategies for designing proteins.
“One is rational design – where you try to go back to first principles and modeling protein structure and design something that fits into an active site or a binding pocket that has a specific effect.”
This first option can be difficult, as it requires an in-depth knowledge of how the target proteins will interact. Essentially, it is the process of building a functional molecule from the ground-up, with full understanding of how to achieve the desired behavior in the finished molecule. The second option, Liberles said, requires substantially less specialized know-how.
“The other is to try and evolve something where you have to design your selection properly,” he explained, “but you don’t have to know much about the details – you let it find the solutions that are possible.”
The Harvard researchers took the second option and were able to develop a system that harnesses the infinite creativity of living systems to produce new proteins. The team refers to their system as phage-assisted continuous evolution (PACE for short) and discussed its innovations in a February 25 release on the Harvard Gazette website.
According to the Gazette article, “researchers have equipped PACE with a negative selection — the ability to drive evolution away from certain traits — to enable the rapid evolution of molecules with dramatically altered properties. That ability, (head researcher David Liu) said, could help researchers to evolve proteins to selectively perform surgery on only one exact part of a human genome, or bind only one disease-causing protein in a sea of beneficial proteins.”
Traditional, directed-evolution-type systems only use a positive selection. That is, they can drive proteins toward certain properties, but have no capacity to penalize the development of unwanted properties. Introducing a technique for negative selection corrects this limitation.
Using the new system, the Harvard team was successfully able to develop entirely novel proteins. According to the Gazette, “Liu and colleagues were able to evolve T7 polymerase proteins — enzymes that bind to specific DNA sequences, called “promoters,” and begin transcribing DNA into RNA — to recognize new sequences, and to reject the sequences they initially evolved to recognize in nature.”
Proteins are the workhorses of the microscopic world. Almost every important biological process on earth involves the action of such molecules.
The Harvard team’s success in improving the performance of directed evolution technologies will allow researchers to custom-build proteins with expanded or even entirely new capabilities. These capabilities could lead to drugs that target disease with never-before-seen precision, or generate biofuels with far greater efficiency. When life is allowed to “find a way,” the possibilities are endless.
