[
Curr Top Dev Biol,
2005]
"Life is pleasant. Death is peaceful. It''s the transition that''s troublesome," said Isaac Asimov. Indeed, much scientific work over the last hundred years centered around attempts either to stave off or to induce the onset of death, at both the organismal and the cellular levels. In this quest, the nematode C. elegans has proven an invaluable tool, first, in the articulation of the genetic pathway by which programmed cell death proceeds, and also as a continuing source of inspiration. It is our purpose in this Chapter to familiarize the reader with the topic of programmed cell death in C. elegans and its relevance to current research in the fields of apoptosis and cell corpse clearance.
[
Cell,
1999]
Fluoxetine (a.k.a. Prozac) is well known for its ability to treat clinical depression, one of the most prevalent of all psychiatric disorders. Yet the mechanism by which fluoxetine actually functions to relieve depression is not well understood. Fluoxetine is the best-known member of a class of antidepressant drugs known as serotonin-selective reuptake inhibitors (SSRIs). In popular accounts, their antidepressant action is usually explained in the context of along-standing model of depression called the serotonin hypothesis. According to this model, levels of seratonergic neurotransmission in the forebrain are a key determinant of mood: high activity results in euphoria, low activity results in dysphoria. Depression is said to be caused by chronically low levels of serotonergic transmission. SSRIs interfere with the activity of the serotonin transporter (5-HTT), a reuptake molecule that removes serotonin from the synapse; thus, the putative low levels of synaptic serotonin in the depressed patient are elevated, and depression is relieved. Consistent with this model, many other antidepressants, including tricyclics (e.g., clomipramine) and monoamine oxidase inhibitors, also potentiate serotonergic transmission by interfering with serotonin reuptake or degradation.
[
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.