Scientists Developing High-Speed Microscope for Real-Time View of
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.
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.
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.
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."
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.
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.
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."
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.
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.
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
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.
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.
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