Bioinformatics software aids Ebola research

kusalik and trost

When Brett Trost enrolled in computer science in 2009, he never imagined his University of Saskatchewan Ph.D. research would help international experts study the deadly Ebola virus.

Trost, now a recent graduate, and his supervisor, Dr. Anthony Kusalik, have developed PIIKA, a new software system currently used by the U.S. National Institutes of Health's integrated research facility in Maryland to study how Ebola infects cells and what cells do to fight the infection.

The Ebola virus, one of the most lethal in the world, causes severe hemorrhagic fever which has case fatality rates of up to 90 per cent.

"Clearly Ebola is a major concern given the unprecedented outbreak in Africa," Trost said. "Better understanding of how Ebola hijacks cell signalling mechanisms will ultimately allow us to develop better treatments."

The team is in the vanguard of a new field called bioinformatics, which combines computer science and molecular biology. When U of S biochemist Scott Napper needed a way to analyze massive data from a new microarray technology used in his cell signalling research, he turned to the computer science team.

The software is tailormade to analyze enzymes called kinases which tell cells how to maintain their normal functions and respond to external agents through signalling pathways. It allows researchers to compare data collected from several protein samples at the same time, making the process faster and more accurate.

The innovative software has been used by U of S graduate Jason Kindrachuk, Napper's former student, at the Maryland laboratory to study several infectious diseases including Ebola. Using the software, scientists can analyze huge volumes of data obtained from kinome microarrays, glass slides containing short protein segments.

"This new software system provides the scientific community with novel insight into the molecular mechanisms of Ebola," said Kindrachuk, who recently returned from Liberia, where he was scientific lead for a diagnostic laboratory that is part of the U.S. government Ebola support effort.

"PIIKA has become a critical tool in my research and will continue to be used because it provides powerful analysis, is easily available to the research community, and is user-friendly."

To help identify potential drug targets for Ebola, liver cell cultures were infected with the virus and the cell signalling responses were observed. Critical signalling pathways were then identified and interrupted with enzyme inhibitors.

The NIH-U of S team, led by Kindrachuk, was able to show in lab tests that if this signalling is interrupted, the virus does not replicate. The procedure also provided partial protection from Ebola in mice. The results were published this summer in the Journal of Virology.

"Scientists compared data collected from infected and non-infected cells, and our software validated their results from other experiments," said Trost, a co-author of the paper.

Trost, whose work is funded by the Natural Sciences and Engineering Research Council, was a U of S recipient of the prestigious Vanier Canada Graduate Scholarship in 2009. He thinks bioinformatics has great potential to improve human health.

"The chance that I might one day play even a small part in improving treatments for human diseases is a huge motivator for me."

- Federica Giannelli is a graduate student intern in the U of S research profile and impact unit.

Article Reference: Star Phoenix