Unfolding Cystic Fibrosis
Small genetic errors, called mutations, can lead to severe human diseases. Among caucasians, cystic fibrosis is the most prevalent, lethal genetic disease, afflicting at least 30,000 people in North America.
Dr. Gergely Lukacs believes that if we understood the disease better at the cellular and molecular level, we could design more efficient therapies. As Canada Research Chair in Molecular Cell Biology of Cystic Fibrosis and Other Conformational Diseases, he is exploring how mutations in the cystic fibrosis gene cause molecular, cellular and organ malfunctions.
Cystic fibrosis is caused by the mutation of a particular gene that helps create sweat, digestive juices, and mucus. Normally, this mutated gene creates a protein that anchors itself to to the outer membrane, or skin, of cells in the sweat glands, lungs, pancreas and other organs. That protein works like a channel, connecting the inner part of the cell to the surrounding fluid and allowing chloride to move into the cell. When the gene mutates, however, the chloride gets trapped outside the cell, where it begins to attract sodium, creating excess salt.
Lukacs’s research has shown that mutations keep this channel from being built, while a small molecular tag called "ubiquitin" appears to speed up the junking of material brought up to the cell surface through the channel. Lukacs uses innovative biochemical, biophysical and morphological approaches to work out exactly what these mutations do to a cell and to the channel.
His research will help us understand the complex molecular machine behind mutant degradation. Once we have a better understanding of how cystic fibrosis develops, we can develop better ways to test for, and perhaps even prevent, this as yet incurable disease.