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Cancer Metastasis Rev,
1999]
Genetic screens in the hermaphrodite nematode worm Caenorhabditis elegans resulted in the identification of the basal conserved machinery of apoptosis, arguably the single most important finding for our understanding of cell death. The last two years have seen enormous progress in the elucidation of the molecular interactions that lie at the heart of this conserved machinery, along with major insights both into how cell death is activated in the worm and into the mechanism of recognition and engulfment of the cell corpses. In this review, I set out the current models of cell death regulation and execution in C. elegans, focussing in particular on the similarities between cell death in C. elegans and vertebrates. Finally, I attempt to highlight key areas for future progress in cell death research in C. elegans and explore additional ways in which the worm can be used to understand the regulation of cell death in mammals.
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Genes Dev,
2001]
In the few years since the discovery of RNA interference, it has become clear that this process is ancient. RNAi, the oldest and most ubiquitous antiviral system, appeared before the divergence of plants and animals. Because aspects of RNAi, known as cosuppression, also control the expression of transposable elements and repetitive sequences, the interplay of RNAi and transposon activities have almost certainly shaped the structure of the genome of most organisms. Surprisingly, we are only now beginning to explore the molecular processes responsible for RNAi and to appreciate the breadth of its function in biology. Practical applications of this knowledge have allowed rapid surveys of gene functions (see Fraser et al. 2000 and Gonczey et al. 2000 for RNAi analysis of genes on chromosome I and III of Caenorhabditis elegans) and will possibly result in new therapeutic interventions.
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Genome Res,
1996]
If world oil prices dropped to zero next year, how would it change the world economy? Investments in oil field exploration would lose their value overnight, whereas shares in a factory making environmentally friendly combustion engines might go up. Everybody would feel the need to plan ahead, and many plans would change. In genetics and molecular biology, DNA sequences are the fuel of research, and their prices are falling dramatically. Within 5 years many complete genomes will be sequenced, and sequence data will be like tap water in Amsterdam-essential for life, but too cheap to measure. A project that was perfectly rational 2 years ago will be a total waste of time tomorrow, and projects that seemed impossible will become feasible. The aim of this review is to explore the consequences for biology of the wealth of DNA sequence data now becoming available. Several bacterial genomes have been sequenced already (Fleischmann et al. 1995; Fraser et al. 1995). The first animal to feel these changes will be the nematode Caenorhabditis elegans, and the worm" will be the focus of this review. The virtues of C. elegans as a model system in biology have recently been sung elsewhere (Hodgkin et al. 1995). In brief, it does everything that makes life interesting (eating, copulating, getting around, and relating to the environment) and manages to do so with only 959 cells, of which 302 form the brain. However, it is likely that much of what is said will apply equally to other species; thus, I hope that the review may also be of some interest outside of the C. elegans community.