Researchers find trove of proteins possibly influencing cystic fibrosis
A new study by researchers at the University of Toronto has identified hundreds of new proteins that could play a role in cystic fibrosis, and which may shed light on why some patients responded better than others to current therapies.
The findings were published in the journal, 'Molecular Systems Biology'.
Many of these proteins -- part of a group of druggable molecules called membrane proteins -- interacted with the CFTR protein, which when missing or faulty led to the build-up of mucous in the lungs and other organs that was often fatal in cystic fibrosis.
"We identified more than 400 proteins associated with either healthy or mutant CFTR, and have shown that some of them could predict the variability seen in patient symptoms and treatment responses," said Igor Stagljar, principal investigator on the study and a professor in the Donnelly Centre for Cellular and Biomolecular Research at U of T's Temerty Faculty of Medicine.
"With a more comprehensive view of the CFTR protein interaction network, we can identify novel drug targets that should enable more patient-specific therapies," Stagljar said.
To help identify protein-protein interactions involving CFTR, the researchers developed a new technology based on a platform they designed in 2014. The approach was a high-through-put version of their Mammalian Membrane Two-Hybrid system, and it allowed for screening of many more membrane proteins that associate with a specific protein.
"The earlier design was array-based, and we could only screen about 200 proteins at a time," said Stagljar, who is also a professor of biochemistry and molecular genetics at U of T. "With this new technology, we've introduced several changes that allow us to screen thousands of protein targets simultaneously, in a pooled manner."
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