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U.Va. Scientists Developing High-Speed Microscope for Real-Time View of Living Cells

January 29, 1999 -- The University of Virginia's Center for Cellular Imaging has received a $1 million grant from the W. M. Keck Foundation of Los Angeles for the further development of a new type of high-speed, high-resolution microscope that will allow medical researchers to visualize dynamic biological processes in living cells. The new high-speed microscopes will make real-time video movies of molecular events in cells as they occur.

Research using these new microscopes is expected to lead to better understanding and treatment of human diseases and injuries such as the spread of tumors, origin of birth defects and spinal cord trauma.

"This grant is allowing us to further develop a new breed of microscope that lets us image real-time molecular events involving proteins inside living cells," says David L. Brautigan, a professor in the School of Medicine and director of the Center for Cell Signaling who is the principal investigator for the project.

Brautigan says protein interactions within cells instruct, or "signal" cells to divide, die, or convert into other types of cells. Visualizing the activity of protein molecules is key to the future development of pharmaceuticals that may inhibit or block the progress of many diseases. "This research is allowing us to answer fundamental questions in cellular and molecular biology that will be used for applied medical research. The instruments promise to provide spectacular insight into the dynamics of cellular signaling events."

"We are building a user-friendly state-of-the-art imaging system that utilizes advanced technology for overcoming the limitations of conventional optical microscopes so that we can record and visualize in four-dimensions, the cellular events as they occur in living specimens," says Ammasi Periasamy, (pictured at right) an optical physicist and biomedical engineer who is director of the Center for Cellular Imaging.

The center was created in 1995 with seed money from the University of Virginia's Board of Visitors as an Academic Enhancement Project grant, and with grants from the National Science Foundation. "This is the second time that the W. M. Keck Foundation has recognized scientific efforts that were initiated by the University's Academic Enhancement Program, the first being the NSF Center for Biological Timing," says Gene Block, vice president for research and public service and director of the Center for Biological Timing.

Periasamy is collaborating with molecular and developmental biologists to design and develop the new microscopes. These microscopes use the physics of energy absorption and fluorescence resonance energy transfer allowing visualization of protein-protein interactions inside living cells. "This gives a display of signaling events rather than physical objects, which are what microscopes have always shown," says Periasamy. "These dynamic events can also be visualized in cells deep inside the tissue using high-resolution non-linear microscopes."

The Keck money will allow further improvements to the system for temporal resolution, creating real-time two-dimensional and three-dimensional moving images of signaling events in cells. This requires ultra-high speed lasers to excite labeled molecules inside cells, and super-high speed detectors to scan a two imensional field of a million points in a fraction of a second.

According to Brautigan, several research groups and individuals are collaborating in the development and use of the microscope facilities, including the interdisciplinary Centers for Cell Signaling, Cellular Imaging, and Biological Timing. Researchers from the School of Medicine, Biomedical Engineering, and the Departments of Chemistry and Biology from the College of Arts and Sciences are also involved.

Currently there are two lead projects using the microscope facilities. One is a study led by Thomas J. Parsons, chair of the Department of Microbiology, who is studying how cancer cells, which are aggressively motile, migrate from one location to another. Using the present microscopes, Parsons and his group have obtained time-lapse images of how proteins assemble adhesions as they "crawl" to new sites where they can establish new colonies. With microscope improvements made possible by the new Keck grant, the researchers will be able to produce real-time movie videos to further their knowledge in this area.

Another study, led by Biology Professor Raymond Keller, is looking at how cells in a developing frog embryo migrate in different patterns to develop a body plan. Keller's group is trying to understand how cells signal to one another in deciding what tissue to become, such as spinal cord, as opposed to skin tissue, for example. One can imagine the information leading to ways to modify or stimulate cell growth, in tumors or wounds.

About two-thirds of the Keck grant will be used for acquiring the advanced instrumentation needed to develop sophisticated microscopes, and one-third for hiring staff and training scientists and graduate students in the use of the new equipment.

The cellular imaging center will be renamed the W. M. Keck Center for Cellular Imaging (http://shiva.bio.virginia.edu/cci/). The W. M. Keck Foundation is one of the nation's largest philanthropic organizations, focusing primarily on higher education, medical research, science and engineering.

FOR ADDITIONAL INFORMATION: please contact the Office of University Relations at (804) 924-7116. Television reporters should contact the TV News Office at (804) 924-7550.
SOURCE: U.Va. News Services

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