Beyond the Genome

Sep 30, 2002

Northern Ohio Live Magazine, October 2002

by Anton Zuiker

Decoding the human genome was a good start. But now the real challenge begins. Genes may be the blueprints for life, telling our cells how to grow and divide, but it’s what cells do with those instructions that determines whether we will be healthy organisms or lifelong DEPENDENTS of the pharmaceutical companies.

In the past, a disease needed to progress into illness before physicians could catch it. Increasingly, though, diseases are being targeted at the cellular level, even before they cause sickness. For many diseases, we now believe, are the result of that process going mysteriously berserk or breaking down. Understanding how the process is supposed to work, and how to tell when it has gone awry, is no simple task, however, given the vast array of proteins at work inside a single cell. How do you begin to sort out what is going on in there, with some things going on underneath or behind other things?

Well, there’s been some progress. The expensive confocal microscope is providing exciting new images. Specific parts or proteins in the cell have been labeled with visible chemical tags so that, as the cells metabolize, reproduce or change according to their genetic instructions, researchers can RECORD the process. Using lasers, the confocal microscope takes pictures, as it were, of minute slices of the cell. A computer connected to the microscope then reconstructs the pictures into a colorful image of the cell, with the fluorescent mitochondria looking like a galaxy in outer space. Seen on a computer screen, the two-dimensional images of the cell, when rapidly shown one after the other, seem to rotate and move; the brain perceives this as three-dimensional.

Kent State University biologist Doug Kline recently used a confocal microscope to record where mitochondria – stained with a fluorescent chemical – were situated inside a bovine kidney cell, and where they moved over time. (Think of the visualizations that accompany a song when you listen to MP3 music on your computer.)

Upstairs, inside Kent’s Cell Imaging and Visualization Center lab, is a giant ImmersaDesk projector, not unlike a large screen projection television. Kline’s cell images can be programmed into yet another computer, and then displayed on the ImmersaDesk. A viewer dons special 3-D glasses, and suddenly the cell is there in full, holographic view.

“There’s an enormous educational use to all this science as well,”says Kent biologist James Blank, director of the school of biomedical sciences. “We’re using the technology to provide students with novel experiences.” Last year Kline worked with students at Kent Roosevelt and Streetsboro high schools. Using Internet connections and cheap 3-D glasses (like the kind you used to wear to watch horror movies), those students could see the Kent researchers’ cell experiments in progress, and interact with the researchers to ask specific questions about what they were seeing. Those pictures will be collected into a library of images that will be available to anyone with a high-speed Internet connection; you won’t need 3-D glasses, because Lee and his assistants will convert the images into a format showing the dimensions of the cell.

But those students took home another lesson, too: Never again will they be able to groan, over their trigonometry homework, that all this pointless math has nothing do to with real life. For these amazing images would not be possible without not only computers but math.

Austin Melton, professor of mathematics and computer science at Kent, who points out that the math involved in deciphering the human genome was so extensive, it had to be divided among numerous computers. Similarly, says Melton, the textbook on how a cell does what it does, and why, will be written in complex formulas and computer programs. In other words, it is good old computational math that will take biological science to the next level. And Melton and his colleagues, biologists Blank and Kline and physicist Mike Lee, are leading that charge. With their cell visualization and imaging project, they could very well be crafting the ways we’ll comprehend cells in the future.

Like physicists discovering smaller and smaller particles of matter, biologists are finding that there are countless proteins and procedures at work within a cell. Take the simple process of a cell’s breaking down a molecule of sugar. To write out the chemical formula that reflects the chain reaction of protein responses in that digestion would fill a classroom white board; but that much is already known, and already documented in scientific databases around the world. What the Kent State team is doing is much more ambitious.

Instead of just modeling known cell activities, they’re attempting to understand the laws of nature and physics that drive a cell, and to predict, with mathematical visualizations, the way a process will play out at the cellular level. “We don’t even know what some of the smallest parts of a cell will look like, so we’re building a mathematical model to predict what they’ll be like,” says Melton. And soon enough, he says, other groups of researchers around the world will come around to this approach.

KSU’s Cell Imaging and Visualization Center project is being funded by a $1.2 million federal appropriation and other grants from the Ohio Board of Regents; nearly $2 million more could be on the way, SAYS Senator George Voinovich, WHO toured the CIVC in July. “I was blown away with what they’re doing,” he told WKSU radio at the time, relating how the image of a human cheek cell stained in red and displayed in 3-D is so different from the science he encountered in school. “With what I saw today, I might have been a physicist.”

In time, says Melton, the KSU team will have a legitimate virtual representation of an entire cell that will allow researchers to replay, and study, a cell’s normal functions as well as test what a cell would do when introduced to some new disease or medication. This research, he says, will eventually help medical technicians detect cancer at a much earlier stage than was ever dreamed possible, making it much easier to nip the disease in the bud.

If, as they say, a picture is worth a thousand words, such images – each constructed from thousands of lines of computer code – will be beyond price.

Anton Zuiker ☄