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NSERC Presents 2 Minutes with David Bundle
On Behalf of the Alberta Carbohydrate Science Group,
University of Alberta, University of Calgary


Summary

Video Name

2 Minutes with David Bundle

Author

NSERC Communications

Duration

3:11

Release Date

September 19, 2012

Description

Amid growing concern that many micro-organisms are becoming resistant to the drugs traditionally used to fight them, The Alberta Carbohydrate Science Group is working to help solve the problem. The five team members are focussing their cross-disciplinary expertise on the function of the glycome—the entirety of a cell's carbohydrates—to determine the fundamentals of cell communication. Understanding the molecular basis of the "glycocode" is necessary to battle human and animal infections through evidence-based design of vaccines that prevent infections and therapeutics that will neutralize toxins. This will help avoid the selective pressure that drives antibiotic resistance.

The research team—David Bundle, John Klassen and Todd Lowary of the University of Alberta; and Glen Armstrong and Kenneth Ng of the University of Calgary—integrates bioanalytical mass spectrometry, protein crystallography, synthetic chemistry and microbiology to make discoveries that are recognized to be at the forefront of glycobiology.

2 Minutes with David Bundle

Transcript
David Bundle

My own field of research is the interface of immunology and chemistry, so I'm particularly interested in carbohydrate antigens that occur on bacteria. And more recently, we've also been looking at toxins which bind to carbohydrates on the surface of human cells. And so, for example, the E. coli toxin that was made notorious by the outbreak of food poisoning at Walkerton, that's a toxin that binds to carbohydrates on the cell surface in order to get into the cell and to do the damage. So we've been studying that in the last 10 years.

This is the E. coli toxin that causes severe kidney failure in people who have E. coli 0157. I's also called hamburger disease. What you can see here is actually two molecules brought together by these very small molecules. Now, this is the toxin molecule minus its enzymic subunit, which is the part that actually does the damage to our cells when this gets inside. But this bigger molecule, the darker blue molecule, this is one we have in our circulation. And it's called serum amyloid P component. So our approach has been to try and stop this toxin from entering the cell.

So what we can do is design a molecule which is a bit like a dumbbell. And one end of the dumbbell binds to the light blue molecule, and the other end binds to the dark blue molecule. And when these two come together, this molecule, which is a bit like a molecular vacuum cleaner, goes around the circulation, picking up debris from dead cells, DNA and so forth, and it takes these molecules out to the liver and disposes of them.

In research, serendipity plays a huge role. And you can't predict exactly what the discoveries will be. I've always regarded research as very much a team effort. It's a team effort of the trainees that are in our group, but also more and more collaboration across disciplines is important. The nice thing about the amalgamation of our groups into a carbohydrate centre has been that we can go all the way from theoretical studies, crystallography, design, chemical synthesis, and then into animals and actually test them. So that's an unusual aspect of the arrangement that we have in this Alberta Carbohydrate Centre.

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