New University Of Colorado Electron Microscopes Provide Cell Images Never Seen Before

The microscopes, which were purchased for a total of nearly $3 million, are furthering the reputation of the molecular, cellular and developmental biology department as a nationally recognized research center, said Distinguished Professor Richard McIntosh. The department already has a three-story tall, 1 million-volt electron microscope that has been used by researchers from around the world since it was acquired by former faculty member Keith Porter in 1972.

"These new instruments are supported by a small fleet of exceptionally powerful personal computers that run programs developed by CU-Boulder researchers to reconstruct parts of cells in 3-D using the mathematics of tomography, just as doctors use a CAT scan or MRI to visualize the head or chest of a patient," said McIntosh. The resulting images reveal aspects of cellular organization at unprecedented resolution in 3-D.

"The Laboratory for Three-Dimensional Cell Structure uses electron microscopy to investigate the internal organization of cells," said McIntosh, who directs the facility. "What makes the addition of these new microscopes important isthat we are able to image portions of cells in three dimensions at a resolutionthat has not previously been possible."

The 3-D lab has been developing technologies with which to image cells at high resolution, using computer-facilitated image processing to reconstruct and visualize cells from a wide range of organisms from both normal and diseased states, said McIntosh.

"The images are providing scientists with a new window on the structural details of cellular organelles, thereby settling some long-standing controversies about how various cellular processes work," he said. "Each of the new electron microscopes stand more than 7 and a half feet tall and are equipped with large control consoles not unlike consoles that are used to control small airplanes."

The 3-D laboratory in MCD biology is being supported by more than $10 million over the next five years, thanks to funds from CU, gifts from local philanthropists, the non-profit Agouron Foundation in Pasadena, Calif., as well as grants from the National Institutes of Health.

On Monday Nov. 26 at 4:30 p.m., the lab will host an open house to demonstrate to faculty, staff, students and the public the newly purchased instruments and the images of cells that have been obtained by electron microscope tomography.

Collection of data for 3-D reconstruction will be demonstrated on the lab’s high-voltage electron microscope, showing how computer control speeds and facilitates modern microscopy. Results from recent studies that have revealed previously unknown aspects of cell architecture will be displayed by computer graphics.

The new electron microscopes can tilt the specimen in various orientations, allowing researchers to take photos of cell "slabs" from 140 different angles, said McIntosh. "We basically get many views of a single slab -- about one-tenth of a cell’s thickness – and then do the same for successive slabs."

The slabs are cut from the cell in "serial order," producing an almost complete picture of the cell in three dimensions, he said.

The new electron microscopes also are equipped with better cameras and a special "electron gun" located at the top of the microscope. "This releases a beam of electrons that penetrate the cell slabs, creating a shadow of the organelles inside," McIntosh said.

Lab personnel include McIntosh, the principal investigator, and David Mastronarde, co-director of the facility. Research personnel include Linda Batlin, Richard Gaudette, Mark Ladinsky, Brad Marsh, Mary Morphew, David Morgan, Eileen O’Toole, Iffat Rahim and Cindi Schwartz.

"The new computers and software, in concert with the microscopes, allow us to get an unprecedented amount of information out of images," said McIntosh, who received his bachelor and doctorate degrees from Harvard University. McIntosh specializes in studying the mechanisms of chromosome movement within cells, including identifying molecules that are associated with cell division.

McIntosh has been a Guggenheim Fellow and American Cancer Society Scholar, the president of the American Society for Cell Biology, and is now a research professor of the American Cancer Society and a member of the prestigious National Academy of Sciences and the American Academy of Arts and Sciences. He also is one of only 18 CU-Boulder Distinguished Professors.