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Past Winner
2003 E.W.R. Steacie Memorial Fellowship

Zongchao Jia

Biochemistry

Queen's University


Zongchao Jia
Zongchao Jia

Fifty years ago, the science of genetics was revolutionized by the discovery of DNA's double helix structure. Today, Dr. Zongchao Jia is creating scientific buzz by turning the same x-ray imaging technique that revealed the secrets of DNA onto the proteins that DNA produces.

"The globular structures of proteins are far more complex than those of DNA," says Dr. Jia, a Queen's University associate professor of biochemistry and winner of one of six 2003 NSERC E.W.R. Steacie Memorial Fellowships. "With DNA, you only have the four base pairs for building blocks. With proteins, you have the amino acids – 20 potential building blocks. So it's a quantum leap in terms of complexity."

X-ray crystallography is the exquisitely challenging science equivalent of shining a flashlight on a child's elaborate Meccano building and then determining the 3-D structure from the shadow on the wall. Crystallographers take atomic-level pictures using intense x-ray beams focused on crystals of the protein. The x-rays, deflected by the atoms they hit, are recorded on detectors similar to those used, for example, in digital cameras. Computers are then used to deduce the intricate 3-D protein structure from the recorded images.

"We like to study the proteins that are the most medically relevant," says Dr. Jia, who is also the Canada Research Chair in Structural Biology.

His lab has led the way in the structural study of anti-freeze proteins. These proteins prevent the formation of ice crystals within cells. This enables some animals to freeze "solid" and thaw (such as with famous demonstrations of frozen frogs) with little or no tissue damage. His lab has identified the structure of four anti-freeze proteins including one in fish and the first ever in an insect. Dr. Jia's research has demonstrated that there are in fact a variety of ways that the different proteins block ice formation. It's work that's critical to the tantalizing possibility of creating ways to reversibly freeze human tissue.

In 1999, Dr. Jia's lab also won what, in essence, was a heated international race to determine the structure of a calcium-regulated protein that plays a role in diseases from Alzheimer's to Muscular Dystrophy and in heart attacks. The protein, calpain, can wreak havoc when it works improperly because it is a protease – it cuts other proteins. It is known to be regulated by calcium. Dr. Jia's atomic-level structural detective work revealed the precise reason that calcium is needed to activate calpain.

"By our identifying the active site, pharmaceutical companies can now try and develop drugs that will block this site, but won't interfere with the hundreds of other proteases in the body," says Dr. Jia.

He's currently just begun work to study cancer-related proteins that could be possible drug targets.

While an NSERC Steacie Fellow, Dr. Jia will continue his groundbreaking work on one of the most biologically important groups of proteins, those involved in phosphorylation and dephosphorylation. These proteins act as on/off switches for almost 30 per cent of the body's proteins. His 11-person lab will focus on phosphorylation proteins that are involved in cellular function, as well as on phytase, an enzyme that liberates the nutrient phosphorus stored in plant seeds. Many farm animals, including pigs, lack this enzyme. At present, phytase is added to agricultural feeds to help increase their nutrient value, but with only limited success.

"Identifying the structure of phytase can help us understand how it works," says Dr. Jia. "Once we understand it, we can then try and improve it through protein engineering, to make it more active and stable for instance."