From Stone Age drawings on the walls of caves to Silicon Age micrographs of atoms aligned in a crystal, humans have created images of that which interests them so others can learn. What most interests Carolyn Larabell, a cell biologist and microscopist with Berkeley Lab's Life Sciences Division, are the proteins inside living cells and the things that they do. To image these proteins and their activities, Larabell has mastered both electron and confocal microscopy and is now blazing new trails with the x-ray microscope, XM-1, at Berkeley Lab's Advanced Light Source (ALS).
"We've been one of the first to do live-cell imaging," says Larabell of herself and her group, meaning that the cells are alive and intact when imaged rather than fixed in a solution or sliced into thin sections as required by other microscopy technologies. "This approach tells both a spatial and temporal story, which is important because proteins are dynamic rather than static."
Born and raised on a farm outside a small town in upper Michigan, Larabell came to be a pioneer in the fledgling field of x-ray microscopy somewhat circuitously, by way of a Ph.D. in zoology from Arizona State University. It was while doing postdoctoral research at UC Davis on developmental biology, that she got involved in electron microscopy in order to image calcium. In 1994 she came to Berkeley Lab to set up an intermediate voltage transmission electron microscope. She soon began working with visible light wavelengths used in a confocal microscope. The dual experience served her well for working with x-rays.
"Microscopists who work with visible light tend to use fast but harsh cell preparation techniques, because at that resolution they won't see their mistakes," she says. "With electron microscopy, every flaw is literally magnified so the preparation techniques are incredibly arduous. Having worked with both, I'm willing to change my protocols to find the best and most efficient."
Larabell's flexible approach has reaped major dividends for the field of cell biology. Her confocal images have graced the covers of numerous scientific publications and her x-ray images are now poised to do likewise. Working with the late x-ray microscope pioneer, Werner Myer-Illse, and others, she has developed a technique for using x-ray microscopy to obtain unprecedented images of labeled proteins inside of whole cells in a hydrated state. Images, produced at XM-1, already show four times better resolution than images from the best visible light microscopes.
"Our ultimate goal is to combine the spatial resolution power of x-ray microscopy with the temporal information you can get from visible light microscopy," Larabell says. "It's a lot of work but I think we're making pretty good progress."