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[
Nat Genet,
1999]
One of the founders of molecular biology, Al Hershey, proffered a vision of heaven, in which one would come into the lab every morning knowing what experiment to do, knowing that it was going to work and knowing that the results would be important. Whether the authors of the Caenorhabditis elegans genome project, published recently in Science felt they had ascended into heaven while performing this gigantic piece of work is unclear, but the project seems to fulfill Hershey's criteria.
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[
Nature,
1996]
During the development of many, if not all, complex organisms, specific cells are marked out for elimination in a process known as programmed cell death, or apoptosis, a form of cell suicide. For example, during the development of the hermaphrodite nematode worm Caenorhabditis elegans, 131 of the 1,090 cells produced are genetically destined to die. Drosophila embryos without the necessary genes to execute this death programme do not survive. In vertebrates, failure to delete malformed or potentially autoreactive immune cells during development can eventually lead to autoimmunity or leukaemia. So too much or too little cell death threatens the whole organism.
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[
Nature,
1996]
Classical results in experimental embryology established long ago that cells of the developing animal have a regional identity. They can be characterized not only as 'skin', 'nerve' and 'bone', but also as 'arm' and 'leg'. But how cells know what body region they belong to, and what to do there, is not known. Results reported in this issue and in Development describe unexpected properties of a key player, one of the Hox genes-the dynamic, lineage-based regulation of a Hox gene in the nematode Caenorhabditis elegans is at odds with a traditional view of Hox genes as relatively fixed markers of regional identity.
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[
Nature,
1998]
Many species rely on chromosome-based systems-such as one X versus two X chromosomes-to trigger the differences between males and females. To do this they must find ways to count the sex chromosomes and to activate the process of dosage compensation, which corrects the imbalance of sex-linked genes. A paper by Carmi, Kopczynski and Meyer on page 168 of this issue brings us closer to understand chromosome counting in the nematode worm Caenorhabditis elegans. The authors have identified an X-linked gene that encodes a protein related to nuclear-hormone receptors. This protein, SEX-1, represses the transcription of
xol-1, the pivotal gene involved in both dosage compensation and sex determination.
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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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[
Science,
1996]
Geoffrey Gold, a physiologist at the Monell Chemical Senses Center in Philadelphia, had wanted for years to put to rest a nagging question: How do odors trigger olfactory neurons to fire off action potentials to the brain? The dogma for the past 5 years had been that odors fall into two catagories, each of which acts via a different inracellular messenger molecule. But Gold believed this view was wrong, and that all odors work by increasing the production of the intracellular messenger cyclic AMP (cAMP). One day last spring, Gold got a phone call out of the blue from neurobiologist John Ngai, at the University of California (UC), Berkeley, offering the possibility of answering this question. It was my dream come true," says Gold. ......
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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.
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[
Nature,
1999]
Advances in human genetics have meant that the genes mutated in human diseases can be identified exclusively by their location in the genome. But how do we work out the cellular functions of the associated protein products? Reports on pages 383 and 386 of this issue begin to address this problem for two proteins - polycystin-1 (PKD1) and polycystin-2 (PKD2) - that are defective in human kidney disease. From their studies of the nematode worm Caenorhabditis elegans, Barr and Sternberg present evidence that homologues of the polycystins act together in a signal-transduction pathway in sensory neurons. Chen et al., by contrast, have used an oocyte-expression system in the from Xenopus laevis to show that a homologue of PKD2 is associated with the activity of a cation channel. These results support the hypothesis that polycystin-related proteins belong to a hitherto unknown class of signal-transduction molecules.
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[
Esquire,
1985]
In the end, it is attention to detail that makes all the difference. It's the center fielder's extra two steps to the left, the salesman's memory for names, the lover's phone call, the soldier's clean weapon. It is the thing that separates the men from the boys, and, very often, the living from the dead. Professional success depends on it, regardless of the field. But in big-time genetic research, attention to detail is more than just a good work habit, more than a necessary part of the routine. In big-time genetic research, attention to detail is the very meat and the god of science. It isn't something that's expected; it is simply the way of things. Those in the field, particularly those who lead the field, are slaves to detail. They labor in submerged mines of it, and haul great loads of it up from the bottom of an unseen ocean-the invisible sea of biological phenomena, upon which all living things float. Detail's rule over genetics is total and cruel. Months and even years of work have literally gone down the drain because of the most minor miscalculations. Indeed, perhaps the greatest discovery in the history of the discipline-the double-helix structure of DNA-might have been made by Linus Pauling instead of James D. Watson and Francis H. C. Crick. But Pauling's equations contained a simple mistake in undergraduate-level chemistry, a sin against detail that is now part of the legend. Each of the six scientists singled out here has made his mark by mastering his own particular set of