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About Sickkids
About SickKids

February 9, 2009

SickKids researchers solve a universal lab test mystery

It is a phenomenon that has boggled molecular scientists for decades … the protein size puzzle. It has to do with a lab test called SDS-PAGE, arguably the world’s most commonly used biochemical lab method. The procedure is used to identify and study proteins. But while it is widely used, it often doesn’t give correct readings for certain types of proteins and scientists have been at a loss to explain why.

A team led by Dr. Charles Deber, SickKids Senior Scientist and Professor in Biochemistry at the University of Toronto, believe they have solved the long standing mystery. The findings are published in the February 10th issue of the Proceedings of the National Academy of Sciences USA.

SDS-PAGE involves taking proteins and encasing them in soap-like detergents. They are then placed on a gel plate, where they move from one end to another. Generally, the smaller proteins move faster and bigger proteins mover slower. Where the proteins end up on the plate determines their size. But for years, researchers have found that readings for one type of proteins - membrane proteins (proteins that surround cells) - are not always accurate.

SickKids scientists have found that the detergent molecules can actually weigh the membrane proteins down.

“The detergent-binding amounts are extremely important, because if the proteins become too heavily encased in detergents, the protein molecules tend to become denatured (lose their original biological shape),” says lead author Arianna Rath, post-doctoral fellow.

Membrane proteins are coded for by 20-30 percent of all human genes, and represent 70 percent of drug targets approved by the FDA in the past decade. When the membrane proteins are absent or dysfunctional, diseases such as cystic fibrosis, diabetes and certain cancers can result.

“The proper identification and study of these proteins is essential. Our findings could help tailor future experiments. Scientists may now be able to determine some of the structural effects of disease-causing mutations, and to use the information to focus on proteins that will be the best candidates for structural studies,” says Dr. Deber.

The research was supported by the Canadian Institutes of Health Research, the Canadian Cystic Fibrosis Foundation, SickKids Foundation and SickKids RESTRACOMP.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. SickKids is committed to healthier children for a better world.

For more information, please contact:

Matet Nebres
The Hospital for Sick Children
Phone: 416-813-6380
email: matet.nebres@sickkids.ca