Researchers develop prototype for whole genome analysis

CAMBRIDGE, Mass. — 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.