Dr. Zongchao Jia
Since a small boy, Dr. Jia watched his parents, both are scientists involved in pharmaceutical research, carrying out various experiments. However, it was not until university time did he realize the excitement and significance of the scientific research. One day, when his father showed him a three-dimensional crystal structure of a drug molecule in atomic detail, he was overwhelmed and fascinated by the fact that individual atoms of a molecule can be directly visualized. From that day on, he made up his mind that one day he would want to study three-dimensional molecular structure himself.
Some 25 years later, Dr. Jia, a professor of the Department of Biochemistry, Queen’s University, is now a Canada Research Chair in Structural Biology and NSERC Steacie Fellow. His research is primarily involved in protein crystallography, a technique used to reveal protein’s three-dimensional structure.
We all know the famous double-helix structure of DNA, the genetic codes of all living organism. In our body, hard at work are the proteins that are encoded by DNA. These proteins are the work horses that perform a diversity of biological function. To fully understand the function of these proteins (i.e. what they do and don’t do, for example) which are usually dictated by their three-dimensional structure, we need to be able to “visualize” the atomic structures of these proteins. First we need to make crystals from very pure protein (these protein crystals are just like table salt and sugar crystals but quite a lot smaller, usually 1/10 of millimeters). The process of crystallization is non-trial and often unpredictable, which is why some would call it “arts” instead of “science”. Once the crystal is obtained, it is bombarded with high-intensity X-ray beam which is very small and highly focused. The X-ray used in the diffraction experiment is similar to the chest X-ray, except much stronger beam is used by the former. Protein crystal will diffract the X-ray and the resulting image of diffraction can be captured by detectors (one type of detector is actually similar to digital camera). The information contained in these diffraction images is used to derive the final 3-D structure.
The detailed 3-D structure can be visualized on graphic computer workstations, with the aid with 3-D goggles (similar to those used in cinema for viewing 3-D movie except much more sophisticated). A picture is worth thousand words! A 3-D structure tells a lot about protein’s function. For example, if a drug molecule is bound to its receptor (a protein that recognizes and interacts with the drug molecule), we can directly visualize the interaction between the protein and drug and see how drug works. And if we look harder, we may even find some room for improvement for next round of drug design!
Dr. Jia’s lab studying a number of important protein families, including cancer-related proteins, proteins related to bacterial pathogenesis, proteins involved in (de)phosphorylation etc. For example, one target Dr. Jia has been working on is called calpain, a calcium-regulated protease that plays a role in diseases from Alzheimer's to Muscular Dystrophy and in heart attacks. The protein can wreak havoc when it works improperly because it is a protease – it cuts other proteins. Dr. Jia's atomic-level structural work, in collaboration with colleagues at Queen’s University, has revealed the precise reason why 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 when necessary, but won't interfere with the hundreds of other proteases in the body," says Dr. Jia.
For further information, please contact Dr. Zongchao Jia using the Email contact form or by phone at 613 533-6277
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