Queen's University

Life on the small scale

Mark BatesMark Bates

 

For his novel research to obtain high-resolution images of biological cells and tissues, Mark Bates, Sc’97, was named the 2010 Grand Prize winner of the GE & Science Prize for Young Life Scientists. Mark won for his essay, “A New Approach to Fluorescence Microscopy,” published in the December 3 issue of Science (www.sciencemag.org).

The essay, based on Mark’s doctoral research at Harvard in 2009, describes his discovery of a new type of “optically switchable” fluorescent molecules, and how these molecules were used for high-resolution biological imaging.

Mark and his colleagues developed a microscope capable of seeing cellular features as small as 25 nanometers in size—10 times smaller than what is possible with a conventional light microscope.

Since the images are obtained using light, which is relatively harmless to the sample, their approach may be used to create time-lapse movies of living specimens with an unprecedented level of detail.

“Our method uses light to probe the smallest structural details of biological specimens. By improving the spatial resolution of the optical microscope by a factor of 10 or more, our goal is to enable researchers to see new aspects of life which have previously been hidden from view.”

Mark and his colleagues developed a microscope capable of seeing cellular features as small as 25 nanometers in size—10 times smaller than what is possible with a conventional light microscope.

At Queen's, Mark studied engineering physics. “I got my start in research while working with the group of Dr. Michael Sayer,” he says. “Professor Sayer was a particular source of inspiration because he was both a great teacher of applied physics and he had a strong intuition for designing practical and meaningful experiments. With his research group I studied functional ceramic materials for sensor applications during my undergraduate thesis year. I also spent a summer at Queen's working with his group.”

After graduation, Mark worked for Celestica, an electronics manufacturing company in Toronto, before moving back into research work. He moved to Montreal to study theoretical condensed matter physics at McGill. “My scientific interests were shifting more and more towards biology, and in particular to biophysics,” says Mark. “To the present day my primary research interest is in biophysics: addressing questions in biology using the methods of engineering and physics. It is my background in these fields which, I think, allows me to approach a biological question from a different viewpoint than other biologists, and to bring a different set of tools to bear on the problem. Historically, the interaction between these disciplines has resulted in important technical advances for biology, such as electron microscopy, X-ray crystallography, and gel electrophoresis.”

After finishing his MSc, Mark moved to Boston and began working as a research assistant in a biophysics laboratory. “I took courses in molecular biology and I enrolled as a doctoral student in the Applied Physics program at Harvard. While at Harvard I worked in the group of Professor Xiaowei Zhuang. Our lab was located in the chemistry department, and our group consisted of researchers from a wide range of disciplines, spanning biology, engineering, chemistry and physics.”

“As described in my essay, my PhD thesis research was focused on the development of a new method for biological microscopy. One interesting aspect to the work was that parts of it happened by chance - we did not set out to invent a new microscope. While carrying out unrelated experiments I was fortunate to notice a previously unreported "fluorescence switching" effect - effectively a fluorescent molecule which emits light that can be switched on and off like a light bulb. After studying the properties of these molecules for some time, their applications weren't obvious until a colleague sent me a paper suggesting link between high-resolution optical imaging and switchable fluorescent molecules. It was then that a fellow graduate student and I formulated an idea for a new way to make images using light, which would be able to see much finer details than a normal light microscope.

“As it turns out, this concept achieves image resolutions 10 times higher than conventional light microscopes, and effectively opens the door to many new research opportunities in biology. The interior of a mammalian cell, for example, is a very complex environment which is difficult to study due to its very small size. Whereas sub-cellular structures would appeared blurred when viewed through a conventional microscope, our method renders the images sharper, and allows the researcher to see more detail. One of the principal advantages of using light to view the sample is that a living organism can tolerate exposure to light, as opposed to the preparation required for electron microscopy which is not compatible with a living sample.”

I would encourage every graduating doctoral student in the life sciences to go through the process of writing that essay - it's a good way to put your work in context and a useful exercise in communicating what can be complicated scientific ideas into terms that a general audience can understand.”

The technology Mark and his colleagues developed is now in the process of commercialization by several major microscope manufacturers. “I'm happy to think that my doctoral research has contributed a new tool which may be used to help answer a wide range questions in fundamental biology, and perhaps also find application in clinical medicine. The GE & Science Prize for Young Life Scientists is a recognition of my thesis work and I am humbled and honored to be the winner for 2010. An important part of the prize is to write a 1000-word essay summarizing your PhD research. I would encourage every graduating doctoral student in the life sciences to go through the process of writing that essay - it's a good way to put your work in context and a useful exercise in communicating what can be complicated scientific ideas into terms that a general audience can understand.”

Mark is now a post-doctoral fellow at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany. There, he applies super-resolution fluorescence microscopy to study the time-dependent internal structure of prokaryotic cells.
 

Queen's Alumni Review, 2011 Issue #1Queen's Alumni Review
2011 Issue #1
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