A few days after conception, humans are still just balls of indistinguishable
cells. The specialized cells of our eyes, skin, muscles and other
component parts are the result of the right genes being turned
on at the right time. Biologists want to understand this process,
and have long sought
to visualize the gene activity in the cells of a developing organism,
or growing tumor.
A team of UCSD biologists recently
pioneered a technique that relies on different colored fluorescent
dyes to label different active genes.
The new technique allows
researchers to simultaneously visualize the activity of multiple
genes in the same cell.
“When using the microscope to measure the fluorescence, the light
is fanned out into a rainbow, and each color is read through a separate
channel,” explains Ethan Bier, the professor of
biology who led the research team. “That way, if the light
is 90 percent blue and 10 percent
yellow, it might look blue to the naked eye, but the microscope
detects each color present.”
Multiplex labeling, as the technique
is called, tags RNA with a fluorescent molecule
to signal that a gene is turned on. When a gene is “on” it
produces RNA copies (gene
transcripts) of itself. The biologists designed fluorescently tagged
RNA molecules that
are complementary to the gene transcripts, and bind to them like
Velcro. Therefore the
active gene appears as a fluorescent beacon.
So far the researchers have used multiplex labeling to visualize
the activity of up to seven genes at the same time, but they predict
it will be possible to increase this to 50.
There are many potential applications for this technique,” says Bier. “For
example,
it could be used to understand how tumors arise and grow, by revealing what
genes are turned on and when. With this information, it should be possible
for cancer
biologists
to predict how aggressive a tumor will be from its early patterns of gene expression.”
“Up until now, visualizing gene transcripts has been more art than science,” says
Dave Kosman, lead author of an August 6, 2004 Science paper describing
the
technique. Kosman, who is a researcher with Bier, and Bill McGinnis, biology
professor,
are both co-authors on the paper. “But we have developed a reliable technique
that is powerful enough to generate a molecular fingerprint of the gene activity
in a single cell,” adds Kosman. 
— Sherry
Seethaler
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