Images of Kc₁₆₇ (top) and S2R⁺ (bottom) cells, from the study by Kiger et al. [1] (reproduced with permission). Wild-type cells are on the far left.

When thinking of genetic screens in Drosophila, the Nobel-prize-winning screens for embryonic developmental phenotypes spring to mind. Loss-of-function mutational analysis has proved to be a powerful approach for dissecting complex processes such as morphogenesis and wing development. But historically the fruitfly community has focused much less on the study of cells in culture. All that may now be about to change. In this issue of Journal of Biology [1], Amy Kiger and colleagues describe the results of a powerful strategy for conducting high-throughput systematic loss-of-function screens in Drosophila tissue-culture cells (see 'The bottom line' box for a summary of the work).

The Perrimon group was very satisfied to see how successfully this pilot screen worked. Having established the 'proof of principle' they have now scaled up to perform whole-genome screens in Drosophila cells in culture (see the 'Behind the scenes' box for more on the development of the work). "It's really changing completely the way we do science," says Perrimon enthusiastically. "Everything now comes down to the assays that we design. You can be as imaginative as you want. We need to do more and more screens and to compile databases of annotated information so that we can build correlations between components of different pathways. The long-term experiment is to see how much of the complexity in the cell can actually be reduced by finding these kinds of correlations."

Completion of the Drosophila melanogaster genome-sequencing project three years ago [2] encouraged the fly community to explore new approaches. "Now we had 16,000 pieces of the puzzle, and working out what they each did was going to be an enormous challenge," says Perrimon. When RNA-interference (RNAi) technology appeared on the scene as a new way of inactivating genes whose sequence is known (see the 'Background' box), it seemed an appealing way to speed up the task of dissecting complex genetic pathways: genes could be systematically inactivated and loss-of-function phenotypes studied on a large scale. But applying the RNAi approach - which had worked so spectacularly in Caenorhabditis elegans [3,4] - to Drosophila proved not to be so straightforward, and early attempts at injecting interfering RNAs into embryos were plagued by technical problems and inconsistent results. It was not until Jack Dixon's group at the University of California in San Diego showed that gene silencing by RNAi works well in fly cells in culture [5] that the stage was set for a screen on the scale that fly geneticists are used to.