Exploring new directions with Ilka Heinemann, PhD
Ilka Heinemann, PhD, and her team at the Schulich School of Medicine & Dentistry spend their time trying to give structure to things that are literally invisible, and by doing so have proven a long-standing belief about how nature works is actually wrong.
Any microbiology textbook will tell you that all DNA replication and RNA transcription always proceed in the same direction and no polymerase (the enzyme responsible for the process) has ever been able to do it in the other direction.
Using X-ray diffraction, Heinemann and colleagues were able to map the tiniest of structures of a protein called tRNA(His) guanylyltransferase with its RNA substrate. What they were able to show is that this protein, responsible for tRNA editing, has a unique property that no one could have predicted.
While it has the same structural core as a forward polymerase, it actually works in reverse. The results were published in the December edition of Proceedings of the National Academy of Sciences of the United States of America.
“The implication of this is that it proves that we were wrong in assuming that polymerases can only go in one direction,” she said. “The question now is, if we know it is possible to go in reverse, why doesn’t nature do it the other way?”
Heinemann is one of Schulich Medicine & Dentistry’s newest researchers. She joined the Department of Biochemistry as an assistant professor in September and when she set out to map the structure of this protein during her post-doctoral fellowship at Yale, she didn’t have any idea that this would be the result.
“That’s what I like about science,” she said. “When you make really cool discoveries, it isn’t always a result of exactly what you set out to do.”
This discovery has opened up a whole host of new questions for Heinemann and her team.
Based on what they have learned from this project, she is now starting to investigate what mechanistically causes this particular polymerase to go in the opposite direction. And if she can determine those mechanisms, the next question is whether they can tweak a forward polymerase to go in reverse.
“What I love about the academic setting is that you are free to chase big ideas,” she said. “I think that’s a lot of fun.”