Amutant protein triggers the chain reaction of cystic fibrosis, says cell biologist Douglas Cyr. This protein, in its normal form, is called CFTR. In a person without the disease, CFTR helps properly hydrate cells that line the lungs. Hydration keeps mucus fluid, allowing it to rid the lungs of particles that could cause infection.

But in people with cystic fibrosis, the CFTR protein functions improperly, causing mucus to become dry and build up, which allows infections to take hold, Cyr says. These infections can eventually lead to lung failure, and ultimately, death.

Cyr and his colleagues identified the problem with the mutant protein — it lies in its assembly, and how other proteins in the cell recognize and destroy it. The findings may have implications for potential drugs for cystic fibrosis, an inherited disease that affects thirty thousand Americans.

“The CFTR protein is kind of like a puzzle,” Cyr says. A cell produces the protein in little pieces that should fit together. But in the mutant protein, tiny sections are missing from these pieces. When the cell tries to assemble the protein, the missing sections cause gaps between the puzzle pieces.

Other proteins keep the cell working properly by destroying things they identify as unusual. Some of those proteins, part of the cell’s quality-control machinery, recognize gaps in the puzzle.

They see the gaps, and then crumble the puzzle, he says.

The problem with trashing the whole problematic CFTR protein, or the whole puzzle, Cyr says, is that it might be able to function properly if the quality-control proteins gave the CFTR protein the chance to survive.

“You can’t rehabilitate a criminal if you give the criminal a death sentence,” Cyr says. “We’ve blocked the death sentence. Now we want to see if the protein can be rehabilitated and live longer.”

The researchers used cells cultured from human embryonic kidney cells, which are similar to cells in the lungs. Researchers analyzed human genes to find proteins that might help maintain the quality of the cell. Then they made those proteins more or less active to see what effect their activity would have on the mutant CFTR protein.

The findings could help pharmaceutical companies develop drugs to repair mutant CFTR proteins. But such advances, if they come to pass, are a long way off. For now, Cyr says he hopes his team can transfer its research from cultured cells to actual lung cells — one more step toward potential application in humans.

Julia Connors was formerly a student contributor to Endeavors.

Douglas Cyr is a professor of cell and developmental biology in the School of Medicine and the study’s senior author. The study was published in the August 11, 2006 issue of the journal Cell.