Jackie Vogel

What Yeast Can Teach Us

By Dustin Driver

Dr. Jackie Vogel examines cell division in yeast at McGill University using microscopes and Macs.

We can learn a lot from yeast. At a cellular level, the tiny organisms mimic many of the processes found in every life form on earth. That’s why Vogel and a team of biologists at McGill University in Montreal are trying to understand exactly how yeast cells divide. In doing so, they hope to disentangle the complex molecular activities that cause cancer.

“We’re interested in trying to understand one highly conserved and fundamental process in all cells, using yeast as a very basic model,” she says. “This is only one aspect of cellular function, but the proteins involved are conserved all the way from yeast to humans. We believe that what we learn by working on yeast will serve as a launch point for what you would call cross-disciplinary interactions to help us understand how these things work in humans.”

Vogel and her team study the structure of proteins that act during cell division using powerful microscopes, high-resolution digital cameras and Power Mac G5s. The cameras generate gigabytes of image files that need to be stored, analyzed and archived for future use. To get the job done, Vogel and her colleagues have built a storage and processing solution using Xsan (Apple’s storage area networking file system), Xserve G5 servers and Xserve RAID. The Apple infrastructure allows Vogel and her team to collaborate with the biology department’s three subdivisions: classic field biology, cell and molecular biology and evolutionary biology.

“We believe that what we learn by working on yeast will serve as a launch point for what you would call cross-disciplinary interactions to help us understand how these things work in humans.”

Deconstructing Cell Architecture with 4D Microscopy

“I’m a yeast researcher,” says Vogel. “I focus on how a cell makes a decision to go through the final stage of cell division — how it separates its chromosomes and undergoes division of the cytoplasm — with an emphasis on how a cell protects and repairs problems in its biomechanical architecture during the process. We’re essentially looking at the signaling within the cell that controls these events in a temporal, spatial way.”

Vogel doesn’t just peer through a microscope to understand cell division; she pours through proteomic studies and teams up with the department’s statistical genetics researchers.

“We use microscopy of living cells that resolves molecules on the basis of time and space, also called 4D microscopy,” says Vogel. “We link this with proteomic studies — how molecules that are involved in these processes are changed over time. There’s also a very useful set of techniques that allow you to query a single gene mutation against mutations in over 70% of the genes in yeast, which is about 6,700. We can bring all these things together largely because we have a really fantastic computer infrastructure for these purposes.”

McGill’s Apple infrastructure allows researchers to efficiently share information regardless of whether they’re using Mac OS X, Windows or Linux. The ease of use and transparency between systems and file formats lets interdepartmental research and new ideas blossom.

Building a Custom Microscopy Lab

The biologists at Vogel’s lab needed more microscopic resolution than most pre-fabricated digital microscopy systems could provide. So they picked their own scopes, software and computers. “Most people go out and buy a system, but we didn’t take that approach,” says Vogel. “We bought parts and put them together into a customized system that would be appropriate for the kinds of things we do. Yeast is very demanding, image-wise. The signals are very small and very weak.”

Vogel and her team use two types of microscopes to scrutinize yeast cells. The first, a wide-field deconvolution microscope, captures images over the course of 15 minutes to an hour with a Hamamatsu ORCAII-ERG digital camera.

“We capture an optical stack (six to 10 frames) every minute or every two minutes or all the way down to every second,” says Vogel. “We are capable of detecting up to three different chromophores at a time from ultraviolet to infrared. And with a digital camera, you can do a lot of tricks to get the best possible images.”

The second microscope, a spinning-disc microscope, can capture up to 30 frames per second. The scope is so fast and detailed that Vogel and her team can watch microtubules and other cell structures growing and changing. The spinning-disc microscope generates between 20 and 30 megabytes of data per second. Typically, Vogel will run the scope for about two to three minutes, capturing up to five gigabytes of data at a time. A researcher in her lab can amass up to 40 or 50 gigabytes worth of image files a week. Any single yeast study can contain thousands of files, which are added to the department’s already vast stores of image data.

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