Researchers from Northwestern University and Yale University have developed a new technology to help scientists understand how proteins work and fix them when they are broken. Such knowledge could pave the way for new drugs for a myriad of diseases, including cancer.
The human body turns its proteins on and off (to alter their function and activity in cells) using “phosphorylation”; the reversible attachment of phosphate groups to proteins. These “decorations” on proteins provide an enormous variety of functions and are essential to all forms of life. Little is known, however, about how this important dynamic process works in humans.
Using a special strain of E. coli bacteria, the researchers built a cell-free protein synthesis platform technology that can manufacture large quantities of these human phosphoproteins for scientific study. The goal is to enable scientists to learn more about the function and structure of phosphoproteins and identify which ones are involved in disease.
Trouble in the phosphorylation process can be a hallmark of disease, such as cancer, inflammation and Alzheimer’s disease. The human proteome (the entire set of expressed proteins) is estimated to be phosphorylated at more than 100,000 unique sites, making study of phosphorylated proteins and their role in disease a daunting task.
“Our technology begins to make this a tractable problem,” said Michael C. Jewett, an associate professor of chemical and biological engineering who led the Northwestern team. “We now can make these special proteins at unprecedented yields, with a freedom of design that is not possible in living organisms. The consequence of this innovative strategy is enormous.”