Researchers at the University of North Texas and the University of Texas at Dallas have, for the first time, modified the compatibility of proteins in cells by building connections at the molecular level that did not exist before.

Proteins are responsible for the functions and properties of living cells. Researchers are working to discover new ways to modify proteins to change the way cells behave to improve the health of living organisms and provide applications for industrial, agricultural and environmental use.

Proteins can be altered by removing part of a protein from one cell and replacing it with a similar part from another protein. However, the joined protein modules are not always compatible and must be engineered through trial and error to produce a successful new protein that can alter the function of a cell. This process is time consuming, and researchers are limited by the availability of compatible biological components.

But that process is being revolutionized by Clement Chan, assistant professor in the Department of Biomedical Engineering and member of UNT’s BioDiscovery Institute, and Faruck Morcos, associate professor in the Department of Biological Sciences and member of UTD’s Center for Systems Biology, who have created a coevolutionary modeling approach that engineers mutations in combined proteins to ensure their compatibility and eliminate costly, time-consuming trial and error.

“We are taking two pieces of a protein that we know are incompatible and are using evolutionary information to engineer these pieces to work together,” Morcos said. “What is innovative is the ability to rationally and effectively modify the compatibility of proteins, and it opens the door to new applications that were not possible before.”

In his lab, Morcos focuses on solving problems at the interface between biology, computation, mathematics and biophysics. He uses molecular evolutionary data to examine thousands of protein sequences and map how the pieces inside a protein are connected. Morcos and Chan have been able to use this computational framework to experimentally alter building blocks within proteins so they are functional.

Chan’s lab creates biomolecular components and devices to control cellular activities and applies engineered biological tools for biomedical, environmental and industrial applications. Once Morcos has developed the computational model of the new protein, Chan synthesizes and tests the new protein to gain further biological knowledge that is then added to the researchers’ database.

“There used to be a huge barrier to finding the right components to create a working hybrid protein,” Chan said. “But now, we can easily build and tailor new proteins that we can use to explore more complex genetic designs and showcase potential applications in understanding molecular communication and synthetic biology.”

The Morcos Lab and Clement Chan Lab research is funded by grants from the National Institutes of Health/National Institute of General Medical Sciences and the National Science Foundation. Their research was recently published in the research journal Nature Communications. The co-first authors of this article are Xian-Li Jiang and Rey P. Dimas, alumni of the Morcos and Chan labs respectively.