Pitt-led research team makes cystic fibrosis breakthrough

Using an ingredient more often found in baking recipes than complicated medical tests, a team… Using an ingredient more often found in baking recipes than complicated medical tests, a team of Pitt researchers has made what could prove to be a major breakthrough in treating the degenerative lung disease cystic fibrosis.

Biological sciences professor Jeffrey Brodsky, along with his team, recently developed a process that monitors the destruction of the membrane protein that causes cystic fibrosis using common yeast.

Brodsky’s observations might lead to the development of new pharmaceutical treatments for the hereditary disease and aid in the testing of future drugs that could potentially block the degradation of the cystic fibrosis transmembrane conductance regulator gene.

CFTR acts as a channel around the membrane cells and regulates chloride levels. Cystic fibrosis results from the imbalance of levels of chloride, other salts and water inside and around the cell.

The imbalance is primarily because of a mutation that blocks the CFTR gene from being transported into the cell membrane.

The team first discovered that new cells were traveling down a pathway that destroyed the protein, which led to further research.

“We wanted to show how human proteins can cause the destruction of cells so we decided to use our tools to better determine how that protein was destroyed,” Brodsky said.

To do so, Brodsky and his team used baker’s yeast to produce the CFTR protein.

“Because human proteins are so unstable, we genetically engineered yeast to understand how it was being degraded and how to develop the yeast cells,” Brodsky said.

The yeast cells allow the team to further research the effects of certain diseases.

“Anytime you want to fight a disease, you have to find out the partners that are elicited by that disease,” Brodsky said. “That is not so easy in humans but the yeast allows us to do that.”

Brodsky came up with the idea to use yeast when he worked with the cells at the University of California, Berkeley.

“The structure and workings of yeast are identical to those of human cells except they are stable,” he said. “Some people are looking into using it for cancer research, but we want to look at other proteins.”

By the conclusion of the study, Brodsky and his team hope to have accomplished three main goals: create new drug targets for cystic fibrosis and other diseases, use yeast to screen for new drugs and determine how cells respond to making bad proteins.

The study still requires further refinement, and Brodsky and his team have yet to achieve all three of their goals.

“We still have not sufficiently engineered the yeast yet, so we have not found a way to use the yeast to screen new drugs,” Brodsky said.

Brodsky worked with Pitt research associate Kunio Nakatukasa, Johns Hopkins University professor Susan Michaelis and research associate Gregory Huyer, but they performed most of the research in Pitt laboratories.

“The big advantage of doing this at Pitt is that it is one of the select number of research centers for cystic fibrosis,” Brodsky said. “It makes it easier for us to interact with each other, and that helped us along the way.”