If you think of a modern genetic research lab as a bakery, then antibodies are the flour. Antibodies are short segments of proteins that bind to modifications in histones, or proteins that act as spools around which DNA winds. Scientists doing genetic research need to identify the effects of these histones on gene regulation, so the antibodies are an essential ingredient for their work. Just like a bakery couldn’t stay in business very long without a good source of high quality flour, a genetics lab relies on having consistent batches of high quality, reliable antibodies to do their work.
But an “antibody bottleneck” has plagued genetics research. Antibodies generated from animals can vary in quality and efficacy, and considerable resources are spent developing and testing them. But Shohei Koide, PhD, professor of biochemistry and molecular biophysics at the University of Chicago, has found a way to break this bottleneck and create an unlimited supply of top notch antibodies for research. Kevin Jiang has more in our Newsroom:
Koide and his team harnessed the power of directed evolution, a method that mimics natural selection and protein design. They first created a large catalog of bacteria that were programmed with artificially synthesized, recombinant DNA to produce different antibodies. After isolating a single antibody that appeared promising in recognizing histone modification, the team analyzed its structure in detail to look for possible improvements. Based on this analysis, they created another set of recombinant DNA, programmed bacteria with it and looked for a new, improved antibody.
They repeated this iterative process of analysis and improvement until they created a sequence of recombinant DNA that produced a highly reliable, reproducible and specific antibody suitable for histone modification research.
Koide’s work was published Aug. 18 in Nature Methods. Read more about his lab and their work using synthetic approaches to understanding how proteins work.
Hattori T., Taft J.M., Swist K.M., Luo H., Witt H., Slattery M., Koide A., Ruthenburg A.J., Krajewski K. & Strahl B.D. & (2013). Recombinant antibodies to histone post-translational modifications, Nature Methods, DOI: 10.1038/nmeth.2605