Natural evolution is a rather slow process based on the gradual accumulation of genetic mutations. In recent years, scientists have found what’s known as ‘directed evolution’, which accelerates this process on a small scale, allowing them to rapidly create new proteins and other molecules in laboratories.
Now researchers from MIT have developed a robotic platform that can run 100 times more directed evolution experiments in parallel and find a solution to a larger population, while simultaneously tracking their evolution. In addition to helping develop new molecules faster, the platform is expected to help researchers simulate natural evolution and answer fundamental questions about how it works.
New system ‘babysits’ viruses
Noting that directed evolution is more of an ‘art’ than the engineering discipline and science aside, Kevin Esvelt, assistant professor at the MIT Media Lab and senior author of the study, states that this is only true until we can systematically explore different permutations and observe the results.
About 10 years ago, Esvelt, a graduate student at Harvard University, developed a way to accelerate directed evolution. In this approach, Esvelt took advantage of bacteriophages (viruses that infect bacteria) to help proteins evolve faster towards a desired function. In this continuous process, each mutation took about 20 minutes and was repeated many times without the need for any human intervention. Guided evolution using this method, known as phage-assisted continuous evolution or PACE, was able to perform 1 billion times faster than conventional directed evolution experiments.
As explained in the Nature Methods article, the new phage and robotic-assisted technique called PRANCE can grow 100 times more populations in parallel using different conditions. In the PRANCE system, each viral population is followed by a robot as it evolves. When the virus succeeds in producing the desired protein, a fluorescent protein is produced that the robot can detect.
“The robot can babysit a virus population by measuring this data, which allows it to see if viruses are performing well or are really struggling and if something needs to be done to help them,” writes research team member Erika DeBenedictis. This means that the new system can help prevent the extinction of viruses that have difficulty in surviving and help the targeted protein evolve as desired.
The new system may also shed light on the historical past of the universe.
Researchers are now using PRANCE to make new small molecule drugs. Other possible applications for such large-scale directed evolution include trying to develop enzymes that break down plastic more efficiently, or molecules that can regulate the epigenome.
This new system could also help scientists better understand the process that led to a particular evolutionary outcome. Thanks to the system, scientists can examine many populations in parallel; can adjust for factors such as the mutation rate, size of the original population, and environmental conditions, and then analyze how these variations affect the outcome. Such a large-scale, controlled experiment could also potentially answer fundamental questions about how evolution occurs naturally.
“Our system allows us to actually realize these evolutions by greatly better understanding what is happening in the system,” says Emma Chory, one of the research team, and says, “We can learn not only the end point of evolution, but also its history.”
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