Houston, Texas, USA: A new platform will help create designer human proteins in the lab, scientists said in a new research study.
Proteins, the end product of genes, carry out life functions. Most human proteins are modified by a process called serine phosphorylation — a chemical switch that can alter their structure and function. Malfunctions in this process have been implicated in diseases such as cancer and Alzheimer’s yet are difficult to detect and study. A group of researchers from Yale University and Agilent Technologies have developed a synthetic biology technique that turns bacterium E. Coli into a phosphorylated protein factory capable of churning out every known instance of this modification in human proteins.
“We synthesized over 110,000 phosphoproteins from scratch and we can now study how they all function together,” said Jesse Rinehart, associate professor of cellular and molecular physiology at the Systems Biology Institute and senior author of the research. “This is the future of scientific research — we can build everything we study.”
Previously, researchers were only able to create a single phosphoprotein at a time. The new platform will help scientists create designer proteins by studying the impact of phosphorylation on all potential protein interactions, the authors say. “Biologists want to know which proteins interact with each other because diseases can arise when these interactions go wrong,” said Karl Barber, a Yale graduate student who is the first author on the study and a recently named Schmidt Science Fellow.
“…These phosphosites retained important binding characteristics of the native human phosphoproteome, as determined by motif analysis and pull-downs using full-length phosphoproteins. This technology can be used to interrogate user-defined phosphoproteomes in any organism, tissue, or disease of interest.” the researchers said.
Other authors include Yale professors Farren Isaacs and Mark Gerstein and Jeffrey Sampson of Agilent, which has applied for a patent on the technology along with Yale. The study was primarily funded by the National Institutes of Health.
The new research study was published in the journal Nature Biotechnology.