New platform will help create designer human proteins in the lab

A synthetic biology technique, developed by a team including Yale researchers, could help to understand the formation of diseases like cancer and Alzheimer’s.
A tailor measures a dress dummy surrounded by models of human protein strands as seen under a microscope.

(Illustration by Michael S. Helfenbein)

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.  

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 research was published in the journal Nature Biotechnology.

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