University of Saskatchewan

July 24, 2014   

U of S Researcher Unravels Secrets of DNA

Szafron shows off his computer model that mimics unraveling (Photo Credit: Scott Bell)
October 19, 2009

By Ishmael Daro

Michael Szafron has been trying to solve a mystery for over a decade—how our DNA untangles itself within the cell.

Knowing exactly how this happens could lead to the development of drugs that kill harmful cells by simply inhibiting the untangling process. This could have important implications in cancer treatment.

Using computer models, the University of Saskatchewan part-time post-doctoral student and sessional math lecturer hopes to shed light on an area of genetics few people have researched before.

DNA is tightly coiled and tangled within the nucleus of a cell. To replicate, it first needs to unknot itself with the help of enzymes known as topoisomerases, which cut and reattach tangled DNA strands.

“If you can somehow discourage these topoisomerases from doing their job, you can then discourage the replication process and therefore selectively mutate or kill cells,” says Szafron. But before that can happen, more needs to be learned about the topoisomerase enzymes.

Specifically, it is not known whether they attach themselves to strands of DNA randomly or whether there is a system in place.

Szafron is not a geneticist or a biologist, but approaches the problem as a mathematician. “Traditionally, math has always been based on solving some real-life problem. So it’s natural that mathematics and molecular biology are so interlinked,” he says.

His computer models are the first step in mimicking how DNA gets unknotted and, in time, he hopes to have enough information to show why the enzymes behave as they do.

Szafron and his PhD supervisor Chris Soteros will submit his preliminary findings to a peer-reviewed journal later this year. They will outline the unique computer models Szafron developed with federal Natural Sciences and Engineering Research Council funding, as well as the probabilities of certain kinds of knots developing within those models.

In the meantime, Szafron will continue collecting data. But even with the simple computer models and the powerful Westgrid computer grid available at the U of S, the greatest challenge he faces is technology.

“If I started it and let the computer simulation run, it would take years to get enough information,” he said.

Instead, Szafron continually tweaks his simulations in order to cut down processing time and, hopefully, understand the enzymes much sooner.

Szafron started thinking about unravelling this mystery back in 1998 while attending a conference in Berkeley, California. He learned how little was known about the effect of enzymes on unknotting DNA and decided he was the person for the job.

He pursued his masters and his PhD, becoming one of the first mathematicians to study the unknotting effect of enzymes. While doing research for his PhD, he read more than 170 different resources from such diverse fields as computer science, statistics and molecular biology.

He decided to write his dissertation as a practical guide allowing people new to the field to get up to speed in months, rather than the years it took him.

Some professors in California—at San Francisco State University and the University of California at Santa Barbara—are already using Szafron’s research as the teaching tool he intended.

Szafron also relied on his dissertation to train two undergraduate students who worked with him over the summer, both of whom were able to get up to speed on the enzyme problem and even help Szafron run the computer models.

For Szafron, the most exciting part of his research is seeing mathematics solve real-life problems and hopefully lead to a medical breakthrough like improved cancer treatment.

"I've been fortunate enough to have that ability (to do math), so I don't want to waste my superpower,” he laughs. “I want to try to do something good with it."

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Ishmael Daro is a third-year political studies student and a Sheaf editor working with U of S research communications through its Students Promoting Awareness of Research Knowledge (SPARK) program.

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