Researchers from Northwestern and Yale have developed a user-friendly technology to help scientists understand how proteins work and how to 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 has a nifty way of turning its proteins on and off to alter their function and activity in cells: phosphorylation, the reversible attachment of phosphate groups to proteins. These “decorations” on proteins provide an enormous variety of function and are essential to all forms of life. Little is known, however, about how this dynamic process works in humans.
Using a special strain of E. coli bacteria, the researchers have built a cell-free protein synthesis platform technology that can manufacture large quantities of these human phosphoproteins for scientific study. This will enable scientists to learn more about the function and structure of phosphoproteins and identify which ones are involved in disease.
“This innovation will help advance the understanding of human biochemistry and physiology,” says Michael Jewett, chemical and biological engineering.
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,” Jewett says. “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.”
As a synthetic biologist, Jewett uses cell-free systems to create new therapies, chemicals and novel materials to impact public health and the environment.
“This work addresses the broader question of how can we repurpose the protein synthesis machinery of the cell for synthetic biology,” he says. “Here we are finding new ways to leverage this machinery to understand fundamental biological questions, specifically protein phosphorylation.”