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[
Nat Methods,
2006]
RNA interference (RNAi) and automated high-throughput screening is a promising combination. But the first systematic large-scale mapping of genetic interactions in an animal shows that manual methods still have advantages over sophisticated automated screens.
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[
Nat Genet,
1992]
Predicting coding regions from genomic sequence is not entirely accurate, and predicting expression patterns of candidate genes is still a fantasy. Both of these concerns can be addressed by analysing expressed sequences (cDNA) in addition to genomic sequences. The genomic sequencing of the nematode Caenorhabditis elegans has begun; in parallel, several groups (including the genomic sequencing participants) are isolating, sequencing and mapping C. elegans cDNA clones. The first results of this endeavor, including the analysis of about 1,600 independent cDNA sequences, appear in this issue.
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[
New York Times,
1991]
Through a microscope, they look like tiny crystal serpents, curving and slithering across the dish with an almost opiated languor, doubling back on themselves as though discovering their tails for the first time, or bumping up against a neighbor clumsily and then slowly recoiling. Beneath their translucent skin the pulsing muscle cells and nerve fibers are clearly visible, a sight so strange and so exquisite that it is hard to believe these creatures are common roundworms, found in gardens and compost heaps everywhere. And it is harder still to believe that such slippery squiggles of life are fast changing the face of fundamental biology.
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[
Nature,
1998]
The human genome is predicted to contain between 50,000 and 100,000 genes. To work out what these genes do, an array of techniques is needed to evaluate the protein-protein interactions and biochemical pathways of any gene product. The nematode worm Caenorhabditis elegans is an excellent system for such studies because of its well-understood genetics and development, evolutionary conservation to human genes, small genome size and relatively short life cycle. The 100-megabase-pair genome will be completely sequenced this year, and a total of 17,000 genes have been predicted, many with human counterparts. Approaches used to manipulate gene expression in C. elegans include transposon-mediated deletion, antisense inhibition and direct isolation of deletions after mutagenesis. Although these methods have proved useful, limitations still exist.
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[
Nature,
1998]
Cytochrome c leads a double life. When a cell is called on to commit apoptotic suicide, cytochrome c relocalizes from the mitochondria to the cytosol. There, it helps to activate the foot-soldiers of apoptosis - the death proteases known as caspases. How cytochrome c escapes from the mitochondria is still a matter of debate, but it is clear that certain elements within the apoptotic regulatory hierarchy do not condone such behavior. In particular, overexpression of the cell-death suppressors Bcl-2 and Bcl-xL prevents the release of cytochrome c, suggesting that these proteins act upstream of cytochrome c in the pathway to death. However, on pages 449 and 496 of this issue, Zhivotovsky et al. and Rosse et al. show that Bcl-2 can also protect cells downstream of cytochrome c release, forcing a re-evaluation of this newly acquired dogma.