A team of University of Saskatchewan researchers are using the Canadian Light Source synchrotron to reveal how cystic fibrosis makes the lungs vulnerable to infection. Their findings, which have been published in the Proceedings of the National Academy of Sciences, uncover a previously unknown function of the immune system which has the potential to benefit those with cystic fibrosis.
The team, led by assistant professor of physiology Juan Ianowski, discovered that the lungs respond to inhaled bacteria by producing airway surface liquid (ASL), a mucus that traps bacteria, dust and other foreign particles to be swept out of the lungs by tiny hair-like cilia.
“So far it is very promising,” Ianowski said. “The research has shown that the secretion of ASL is absent in cystic fibrosis patients.”
ASL also has bactericidal properties, not only trapping potential disease-causing microbes, but deactivating and killing them. Over the last decade, scientists have hypothesized that in cystic fibrosis a mutation to a particular gene interferes with the production of ASL. The lungs of patients with the mutation fail to produce ASL as a response to inhaled irritants and other threats.
“The mucus is a critical aspect in cystic fibrosis… it’s not the cystic fibrosis that kills you but the infection that follows,” said Dean Chapman, a professor of anatomy and cell biology and co-author on the PNAS paper. Chapman holds the Canada Research Chair in X-ray imaging and also leads the biomedical imaging and therapy beamline at the CLS.
The team’s research suggests that the use of antibiotics to help the lungs secrete ASL may improve lung function in cystic fibrosis patients.
“No question, this is the highest-profile work we’ve done on this beamline so far,” Chapman said. “I think this will help answer some of the issues around cystic fibrosis and the creation of the mucus, because the bacteria are ultimately what cause death.”
Until recently, it was unknown if bacteria triggered the production of ASL in the airways. By using the synchrotron, the research team developed a new technique to measure ASL by exposing swine tracheas to bacteria that cause health problems with cystic fibrosis patients. The test animals all prompted increased secretion of airway fluid, confirming the role of ASL and therefore the effects of cystic fibrosis.
“Using the agar beads as a vehicle to get the bacteria into the trachea we could measure mucus creation,” Chapman said. “The beads were tagged two different ways: some had bacteria and some didn’t. That helped us understand if the bacteria had a role in the creation of mucus.”
The research, which began three years ago, was funded through a grant from Cystic Fibrosis Canada and supports a growing body of evidence that the failure to produce ASL is a primary cause of airway disease in cystic fibrosis patients.
Going forward, the team hopes to perform additional trials on a more powerful beamline and has looked at the idea of using animals with the cystic fibrosis mutation in future trials.
“This will be the beginning of more papers and more research about this topic,” Chapman said. “Soon we’ll be imaging live pigs with the cystic fibrosis genetic defect either later this year or early next year.”
Graduate student Xiaojie Luan was also on the team and was instrumental to the project’s success. “His performance was outstanding. Without him, none of this would have happened,” Ianowski said.
“It took a village to make this work,” Chapman said.
According to Chapman, the most difficult part of the project was securing enough time on the beamline to perform the trials. “Beam time here is limited… most things happen in little increments.”
For Ianowski, the biggest challenge was developing the research methods from scratch.
“It took us the better part of two years to get the technique working,” Ianowski said. “Once we had the technique, it took us about a year to get results.”
Chapman attributed the success of the project to the collaboration of many colleges and disciplines.
“What makes this extraordinary is that the synchrotron is on campus,” Chapman said. “I don’t think there’s another synchrotron that is suited as well for this kind of work. Having it on campus is a tremendous opportunity.”
Photo: Supplied/Canadian Light Service