Researchers develop prototype for whole genome analysis
CAMBRIDGE, Mass. (Dec. 9, 2004) — One of the
best ways to discover a gene’s function is to
disable it and then see how that affects the cell. But
doing this for an entire genome is a complicated process
requiring a great deal of time and machinery. Researchers
at Whitehead Institute for Biomedical Research, however,
have developed a prototype for testing every gene in
a whole genome using only four glass slides.
This platform, described in Nature Methods, harnesses
the power of a new technology called RNAi (shorthand
for “RNA interference”). Scientists synthesize
small RNA molecules designed to target and “knock
out” a specific gene by blocking its ability to
create protein. And since each RNAi molecule is specially
designed for its target gene, studying a 20,000-gene
genome, such as the fruit fly, would require generating
20,000 RNAi molecules. Whitehead scientists invented
a process in which this can be done much more simply.
“Our experiment was proof of principle,”
says Douglas Wheeler, a technical assistant in the lab
of Whitehead Associate Member David
Sabatini. “We proved that this technique has
the potential to scale up and test a whole genome on
just four glass slides.”
In order to test these principles, Wheeler printed
384 RNAi molecules onto a slide and then covered it
with a cellular matrix. Each RNAi was absorbed into
a different cell where it knocked out its designated
gene. Wheeler was then able to glean insights into these
disabled genes by examining how their loss of function
affected each cell.
Currently, Wheeler is working on using this technique
to test the entire fruit fly genome.
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