Emory chemist Monika Raj will apply the grant to advance a new approach aimed at repairing malfunctioning proteins that drive disease. Photo by Kira Walsh.
The W.M. Keck Foundation has awarded Emory University chemist Monika Raj a three-year, $850,000 grant to advance a novel approach aimed at repairing malfunctioning proteins that drive diseases such as cancer and inherited disorders.
Proteins inside each of our cells act like tiny machines that do everything from catalyze reactions to form cellular structure. A single letter change in the protein’s building blocks, known as amino acids, can be enough to make that machine fail.
The small error can break key connections that the protein needs to function, which in turn leads to the cellular damage and death that cause numerous diseases.
Raj’s project, Targeted Protein Restoration Technology, or PRT, aims to restore protein-to-protein reaction by working directly at the protein level with customizable chemical probes that act like molecular patches.
Instead of replacing an entire protein or rewriting DNA, the patches would bind to the defective protein and help it reconnect with its normal partners, all while leaving the healthy portions intact.
Other modern therapies focus on fixing proteins “upstream,” through gene editing but cannot repair existing errors, says Raj, a professor of chemistry in Emory College of Arts and Sciences.
“It’s a very high-risk, high-reward project,” Raj says. “We are using machine learning and artificial intelligence tools to figure out the right binder and then replace the altered amino acid with a mimic of wild-type amino acid.”
The Keck award encourages discovery for more than long-term medical use. Because Raj designed the approach to be programmable and reversible, it could provide more precise control than permanent gene edits in situations where researchers want to “turn” protein function on or off and study what happens.
This will allow scientists to test the importance of single amino acids and even add chemical modifications to give proteins new properties. That work could reveal how the small chemical changes that cells add to proteins alter function in health and disease.
The project “reflects a broader mission of utilizing organic chemistry tools in the field of biology,” says Riley Hughes, a third-year graduate student who works alongside Raj in her lab.
“Support from the Keck Foundation enables us to pursue this research at a world-class level and may open the door for entirely new discoveries at the protein level,” Hughes adds.
Simon Blakey, chair and professor of the Department of Chemistry, adds that the grant will help point researchers towards cures for diseases that currently cannot be treated.
“This grant provides an exciting opportunity for Professor Raj to develop a creative new approach to understand and tackle disease resulting from genetic mutations, by addressing the mutations downstream at the protein level, complementing traditional genetic approaches,” Blakey says.
“The W.M. Keck Foundation is known for identifying high-risk, high-reward work capable of breaking open new territory,” he adds. “These are the hallmarks of Professor Raj’s research program.”