Seeing the shimmer of biology in action pg. 4
“So we have effectively a light bulb inside the cell,” Jansen says.
That light bulb is really quite weak—the mice do not actually glow like fireflies. But some of the photons of light do make their way out of the animal, and sophisticated charge couple device (CCD) cameras, cooled with liquid nitrogen to minimize noise, can capture them. Imaging systems such as those produced by Xenogen, which are available to Vanderbilt scientists via the new Institute of Imaging Science, make the process relatively straightforward. The systems manage everything from administration of the inhaled anesthetic to quantitation of the detected light.
Tumor cells were the early front-runners in the “cells-to-watch” category.
“It’s a pretty well-established paradigm now to incorporate a luciferase into a tumor cell line, implant those modified cells into animals, and then monitor the luciferase activity to find where the tumor cells become established and to follow the growth of the tumor,” says J. Oliver McIntyre, Ph.D., research professor of Cancer Biology at Vanderbilt.
And because of the high sensitivity of bioluminescence, the very early stages of tumorigenesis and of metastasis are open for study.
“Bioluminescence imaging lets us detect very small numbers of cells—in the hundreds—from the internal organs of a small animal,” says P. Charles Lin, Ph.D., associate professor of Radiation Oncology at Vanderbilt. “There is no other way right now to detect those cells.”
Watching tumor growth and metastasis in real time gives investigators a window to a tumor’s molecular environment and to its susceptibility to therapeutic interventions. McIntyre, who works with Lynn M. Matrisian, Ph.D., professor and chair of Cancer Biology at Vanderbilt, describes how the group has used bioluminescence to study the effect of an enzyme called MMP-9, which “chews up” the matrix material between cells, on tumor growth.
Heath Acuff, Ph.D., at the time a graduate student in the group, compared the establishment of lung tumors in mice with and without MMP-9. Luciferase-expressing tumor cells were injected into the tail vein of mice; they then homed to the lung and grew, and the investigators followed their growth by looking at the light being produced.
Mice lacking MMP-9 had fewer tumors at the end of the study, and by following the mice over time, the investigators knew this difference occurred very early, within the first 24 hours.
“The imaging really provides this temporal information from individual animals or groups of animals that is not so easy to obtain by other methods,” McIntyre says.
Shining light on a diabetes therapy
The high sensitivity of bioluminescence imaging was just what Alvin C. Powers, M.D., director of the Vanderbilt Diabetes Center, needed to track his favorite cells—those that populate pancreatic islets. Islets—so-named because they appear to be small cellular “islands” within the pancreas—are home to the insulin-producing beta cells and several other hormone-releasing cell types.
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