How does nature make new things that have new functions? How does it make something simple into something more complex? Evolution.
In nature, evolution is manifested in the progression of changes in the genetic composition of all organisms over generations as they adapt to altered living conditions. Researchers have been studying nature’s process of change for more than a century in a desire to understand it and, in the lab, control or direct evolution at the molecular level at an unprecedented rate.
Molecular evolution (the process of evolution at the DNA, RNA, and protein level) emerged as a field in the 1960s, so it’s inevitable that the field itself has also evolved.
“Over the past 30 years or so, scientists have figured out how to use some of the mechanisms that biology uses for evolution – extracting the tools for evolving molecules out of biological systems and putting them into the hands of laboratory investigators,” says M.G. Finn, professor and chair in the School of Chemistry and Biochemistry at the Georgia Institute of Technology, and a researcher with the Petit Institute for Bioengineering and Bioscience.
“We’ve learned how to bring that knowledge into the lab, and those techniques are now routine, and reasonably easy to use once you know how,” says Finn, who first proposed the creation of the Molecular Evolution core facility, which launched last year in the Roger A. and Helen B. Krone Engineered Biosystems Building.
But the techniques are still advanced enough so that most biomedical researchers don’t actually have the know-how. That’s where the Molecular Evolution core comes in. While most core facilities are built around sophisticated equipment, this one is centered on the design and execution of experiments that involve molecular evolution techniques, such as phage display, SELEX, and yeast hybrid selection methods, which provide access to peptides, proteins, and polynucleotides with an immense range of properties.
“We can train people to do simple molecular evolution,” says Anton Bryksin, technical director and day-to-day manager of the Molecular Evolution core. “My basic mission is to train students, post-docs and research scientists across campus in applying these molecular evolution techniques to their own work.”
To be sure, the sophisticated equipment is there in the 1,000-square-foot facility: next generation sequencing (NGS) machines (Illumina MiniSeq and NextSeq500), a QPix II colony picker, BluePippin Pulse Electrophoresis system, Bioanalyzer 2100, and a Beckman Coulter Z2 cell and particle counter, among other things.
“Our services are demand-driven, by researchers from across campus, and also driven by my own research,” says Bryksin, whose current work is focused on bacterial surface display that allows efficient expression of different proteins on the surface of bacterial cells. “Cells expressing proteins on their surface can be used to produce small particles – outer membrane vesicles, or OMVs, that also contain biologically active proteins. We are now trying to see whether OMVs can be used as delivery vehicles to bring biologically active proteins toward specific targets.”
Meanwhile, Bryksin and lab technician Naima Djeddar, are helping to guide a number of different Petit Institute researchers in the techniques involved in directing the evolution of molecules. An evolutionary process that takes generations in nature, may take only days with skilled direction.
“The Molecular Evolution core is somewhat different, in that techniques are chosen for the problem at hand, and then investigators are trained in whichever of those are most appropriate,” Finn says.
Prospective core users can submit their request and expect high quality results with a relatively quick turnaround time, according to Steve Woodard, assistant director/core facilities, who oversees core facilities in the Petit Institute.
“Phage display is one of the services that makes the molecular evolution core unique and valuable on the Georgia Tech campus, and in the region,” Woodard says. “Dr. Bryksin also has the ability to aid the evolutionary selection with in-silica analysis, thus rationally designing selection libraries in the computer, producing them, and then testing their binding or other properties.”
Directing the evolution of something takes a lot of technical skill. The researchers who could take advantage of such skills are wide ranging, but would include anyone making a nanoparticle that targets a specific cell type or a molecule that binds to a particular protein.
“In our own lab, we’re trying to evolve a new class of enzymes, which uses the same kinds of tools and designs,” Finn says. “When you start thinking about designing experiments using evolutionary tools, you find the same principles come up over and over again.”
He believes it be the first and only core facility devoted to the techniques of molecular evolution in the U.S., and perhaps the world.
“I can’t emphasize enough the essential role that the Georgia Tech’s administrative leaders played in building this core,” Finn says. “When the idea was presented, they were open and perceptive. The response was remarkable. As a result, now we have a powerful set of new tools at our disposal. It will be interesting to see where we evolve to from here.”
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