Scientists use Saskatoon synchrotron for atom-by-atom look at deadly heart defect

A research team from British Columbia is using the Canadian Light Source synchrotron to understand a genetic mutation that can create an irregular heartbeat.

Heart arrhythmia responsible for death of 40,000 Canadians every year

The Canadian Light Source synchrotron in Saskatoon was recently used to study a genetic condition that can cause irregular heartbeats. (Canadian Light Source Inc, cc-by-sa-2.0)

A research team from British Columbia is using the Canadian Light Source (CLS) synchrotron in Saskatoon to understand a genetic mutation that can create an irregular heartbeat.

Known as heart arrhythmia, irregular heartbeats can come with serious consequences and kills about 40,000 Canadians a year.

One form of the issue is caused by a genetic defect in a protein called calmodulin, which regulates the signals that tell the heart to beat.

"The problem is, if you want to study proteins involved in electrical signalling, every protein is very small," said lead researcher Filip Van Petegem, a professor in the University of British Columbia's Department of Biochemistry and Molecular Biology. "You can't see that with a regular microscope."

Van Petegem's team used the CLS, located on the University of Saskatchewan campus, to study the mutated gene. They fired intense X-rays at crystals of the protein, creating a high resolution, 3D look.

"We can see the individual atoms of the protein," Van Petegem told CBC Radio's Saskatoon Morning.

Researchers then compared the mutated version of the protein with the normal version.

A 3D model of the mutated protein. (Canadian Light Source/Supplied)

"Even though a mutation can be a small change in a very long string of code in the DNA, it can have a very large change in the 3D structure," he said. "It completely changes that protein."

Van Petegem also found different versions of the mutation can have different effects on the heart. 

"That was a major surprise," he said. "Even though they all lead to the same type of arrhythmia, the mechanism by which they do that is very different."

The team was surprised by how the mutated protein was still able to fulfil many of its regular functions in the body, even though it looked nothing like the regular version.

Professor Filip Van Petegem said the research could lead to better treatments for heart arrhythmia. (Canadian Light Source/Supplied)

Now that the team has a better idea of what the mutation looks like, researchers can use that information to develop better treatments. Right now, arrhythmias are treated with beta blockers, which don't always work, and implantable heart defibrillators which start the heart if it stops beating.

"The idea would be to target that bad copy using structural information like the one we obtained to somehow inactivate the bad copy," he said. "It could be a drug that somehow only recognizes the bad copy, another possibility is to use gene therapy."

Van Petegem's work was recently published in the Proceedings of the National Academy of Sciences.


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