Dr. Stacey Wetmore explores the reactions between DNA and various harmful chemicals to understand how DNA is damaged.


Dr. Stacey Wetmore

Professor, Department of Chemistry & Biochemistry
University of Lethbridge
Tier 2 Canada Research Chair in Computational Chemistry

Research area
Dr. Wetmore’s group uses WestGrid and Compute Canada resources to explore the reactions between DNA and various harmful chemicals in order to understand how DNA is damaged, which can lead to cancer and other diseases. She then studies how the natural mechanisms in our bodies are able to repair this damage.

Research relevance
The results of this research have the potential increase our general knowledge of DNA damage and repair processes, which will allow for the design of novel ways to diagnose, treat and prevent disease.

When did you first start using Compute Canada resources?
I initially used Acenet in 2001 when I started as a faculty member at Mount Allison University in New Brunswick. I didn’t have the budget to buy my own equipment and even if I did, it would have taken some time to arrive and set up.

What did that mean for your research?
I could hit the ground running with my entire research project, hire students right away and attract funding sooner. This included grants from the Canada Foundation for Innovation for my own dedicated HPC (high performance computing) resources. Then I got two other CFI grants for HPC resources when I moved to the University of Lethbridge which allowed me to set up two computer clusters, one in Lethbridge and the other at the University of Calgary, with support from WestGrid.

Your research is investigating the mechanisms associated with DNA damage and repair. What are the main research questions you are exploring?
In terms of DNA damage we’re interested in the addition of bulky DNA adducts (widely used indicators of DNA damage), which arise through many different environmental, natural, pharmaceutical and industrial sources. Some show up in charred (burnt) meats, others in pesticides. Even estrogen used in hormone replacement therapies can lead to these adducts. We are using computer models to understand how these adducts affect the DNA.

And what are you trying to discover on the DNA repair side?
Our body has repair enzymes that work to fix DNA damage. We’re interested in the chemistry of how these repair enzymes work. For example, different cancer drugs induce DNA damage as a way to kill the cancer cells. The last thing we want is for the repair enzymes to fix this damage. If we know how the repair enzymes work we’ll be in a better position to try to control their function, which would make cancer drugs more effective.

You’re a chemist, but you don’t have a chemistry lab?
That’s right. I’m a computational chemist. The major equipment for my group is computers, which we use to access Compute Canada infrastructure. In order to look at the chemistry of a DNA helix and understand the interactions with the enzymes that can fix it, we need to physically model every atom that’s in the DNA strand of that enzyme. We’re talking about molecules that live for a very short time, so it’s impossible to learn about them using traditional experiments. The computing power provided by WestGrid and Compute Canada allows me to work with large-scale models at very fast speeds. I couldn’t get any research results back without Compute Canada.

Are there other ways that Compute Canada is helping to support your research?
I relied on the WestGrid technicians in Calgary to help set up these clusters, which is really important when you’re at a smaller university where the technical staff are bogged down with other jobs. Trying to figure out how to run HPC systems is a big task. The WestGrid guys know exactly what they’re doing. For example, we’ve really noticed a reduction in the amount of downtime. You also have access to a database of people you can email to get help from. Not only do they respond quickly, they know the answer right away. This is a huge resource to us.

If Compute Canada tripled or quadrupled the amount of computing power and your time on this resource, could you use it?
Computational chemists could always use more time. In short, more computing time means more accurate calculations on bigger models.

Looking down the road, what are the potential clinic applications of your research?
On the DNA repair side, it could lead to the design of cancer drugs that stop the repair enzymes from fixing the DNA damage that’s needed to kill tumours. On the DNA damage side, it’s important to understand that there are already examples of pesticides that cause these adducts. That research has provided the evidence needed to ban its use. If we can make that connection with other things, then that strengthens our position to influence legislators to stop or limit the public’s exposure to carcinogens.