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Angew Chem Int Ed Engl,
2011]
This Review discusses the potential usefulness of the worm Caenorhabditis elegans as a model organism for chemists interested in studying living systems. C. elegans, a 1 mm long roundworm, is a popular model organism in almost all areas of modern biology. The worm has several features that make it attractive for biology: it is small (<1000 cells), transparent, and genetically tractable. Despite its simplicity, the worm exhibits complex phenotypes associated with multicellularity: the worm has differentiated cells and organs, it ages and has a well-defined lifespan, and it is capable of learning and remembering. This Review argues that the balance between simplicity and complexity in the worm will make it a useful tool in determining the relationship between molecular-scale phenomena and organism-level phenomena, such as aging, behavior, cognition, and disease. Following an introduction to worm biology, the Review provides examples of current research with C. elegans that is chemically relevant. It also describes tools-biological, chemical, and physical-that are available to researchers studying the worm.
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Yakugaku Zasshi,
2008]
Selenium (Se) is an essential trace element. Se is found as selenocysteine (Sec) in Se-proteins. Sec is the 21(st) amino acid, because Sec has its tRNA, the codon UGA and those components in its translational machinery. Sec UGA codon shares with major stop codon UGA. We purified Sec synthesizing enzymes, such as seryl-tRNA synthetase (SerRS), Sec synthetase (SecS) and selenophosphate synthetase (SePS). I described the procedures to prepare Sec tRNA, SerRS, SecS, SePS and [(75)Se]H(2)Se in detail. We clarified that SecS composed of two proteins, SecSalpha and SecSbeta. Sec synthesizing and incorporating systems present in Monela, Animalia and Protoctista but not in Plantae and Fungi. We showed that protozoa had Sec tRNA on which Sec was synthesized from Ser-tRNA by bovine and protozoa SecS. Some worms, such as Caenorhabditis elegans and Fasiola gigantica, also had Sec tRNA on which Sec was synthesized by bovine liver SecS or C. elegans enzymes. We showed recognition sites of mammalian Sec tRNA by SecS. The identitiy units of Sec tRNA are 9 bp aminoacyl- and 6 bp D-stems. This recognition is not the base-specific manner but the length-specific manner. From comparison of the phylogeny trees of Sec synthesizing system and translation system, we concluded that the evolution of Sec synthesizing system is older than that of the translation system.
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J Am Soc Nephrol,
2005]
The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.
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Mechanisms of Ageing & Development,
2005]
Recent results indicate that the longevity of both invertebrates and vertebrates can be altered through genetic manipulation and pharmacological intervention. Most of these interventions involve alterations of one or more of the following: insulin/IGF-I signaling pathway, caloric intake, stress resistance and nuclear structure. How longevity regulation relates to aging per se is less clear, but longevity increases are usually accompanied by extended periods of good health. How these results will translate to primate aging and longevity remains to be shown.
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Exp Gerontol,
2006]
A powerful approach to understanding complex processes such as aging is to study longevity in organisms that are amenable to genetic dissection. The nematode Caenorhabditis elegans represents a superb model system in which to study the effects of mitochondrial function on longevity. Several mutant strains have been identified that indicate that mitochondrial function is a major factor affecting the organism''s lifespan. Taken as a group, these mutant strains indicate that metabolic rate, per se, only affects longevity indirectly. Mutations causing lowered metabolic rate potential are capable of decreasing or increasing longevity.
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Criollo A, Vitale I, Morselli E, Galluzzi L, Markaki M, Megalou E, Maiuri MC, Michaud M, Tavernarakis N, Madeo F, Palikaras K, Malik SA, Kroemer G, Pasparaki A
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Autophagy,
2010]
The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by the established link between caloric restriction and Sirtuin-1 activation, we decided to investigate the putative implication of Sirtuin-1 in the response of human cancer cells and Caenorhabditis elegans to multiple triggers of autophagy. Our data indicate that the activation of Sirtuin-1 (by the pharmacological agent resveratrol and/or genetic means) per se ignites autophagy, and that Sirtuin-1 is required for the autophagic response to nutrient deprivation, in both human and nematode cells, but not for autophagy triggered by downstream signals such as the inhibition of mTOR or
p53. Since the life spanextending effects of Sirtuin-1 activators are lost in autophagy-deficient C. elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy.
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Int J Parasitol,
1998]
Caenorhabditis elegans has become a popular model system for genetic and molecular research, since it is easy to maintain and has a very fast life-cycle. Its genome is small and a virtually complete physical map in the form of cosmids and YAC clones exists. Thus it was chosen as a model system by the Genome Project for sequencing, and it is expected that by 1998 the complete sequence (100 million bp) will be available. The accumulated wealth of information about C. elegans should be a boon for nematode parasitologists, as many aspects of gene regulation and function can be studied in this simple model system. A large array of techniques is available to study many aspects of C. elegans biology. In combination with genome projects for parasitic nematodes, conserved genes can be identified rapidly. We expect many new areas of fertile research that will lead to new insights in helminth parasitology, which are based not only on the information gained from C. elegans per se, but also from its use as a heterologous system to study parasitic genes.
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Mech Ageing Dev,
2002]
It strikes me that among our relatively small community of gerontologists concerned with genetic approaches to our science, there is somewhat of a dichotomization. On the one hand, there are those of us, like myself, who tend to be dour ''complificationists''. Journalists talk to us, but are usually disappointed by the encounter. We are perhaps too impressed with the enormous diversity of genetic modulations of human senescence and with our interpretations of the implications of the evolutionary biological theory of senescence, namely that senescent phenotypes per se are non-adaptive, non-determinative, subject to stochastic events as well as highly polygenic modulations, with resulting wide variability in mechanisms of senescence among and within species. Quite happily, however, there are wonderful optimists among us. They seem to be convinced that there are likely to be a rather small number of major gene effects for a few major mechanisms. They include most Saccharomyces cerevisiae and Caenorhabditis elegans geneticists, some Drosophila melanogaster geneticists, and some mouse geneticists. They also include caloric restriction enthusiasts. Let''s call these colleagues ''simplificationists''. Journalists and friends generally find them to be delightful companions. Where does the truth lie? Perhaps the truth lies somewhere between these two extremes and is largely dependent upon the organisms and the range of environments being investigated.
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J Exp Zool,
1999]
The recent findings that key developmental genes are conserved across animal phyla have led to descriptions of evolutionary change in development based on the recruitment of these few molecules. This approach, however, encounters problems in assigning homology across long evolutionary distances. By contrast, reproducibility of the cell lineage of free-living soil nematodes (order Rhabditida) and conservation of larval blast cells across nematode species permit evolutionary comparisons of developmental mechanisms among nematodes at the cellular level. Such comparative studies uncover an unexpected flexibility of developmental mechanisms: Large evolutionary differences have been described between invariant and noninvariant lineages, in the cellular mechanisms specifying a given cell (for instance, the gonadal anchor cell), in the subcellular events leading to asymmetric divisions (for instance, the first division of the egg), and in redundant networks of cell interactions (for instance, those specifying the centered pattern of vulva precursor fates). Interestingly, redundancy of developmental mechanisms favored by selective pressure allows in turn for evolution of these mechanisms. Such evolutionary changes in developmental mechanisms specifying cell fates can occur in the absence of obvious morphological change, which rather correlates with evolution of cell fates per se: death, division, migration, and differentiation (for instance, in the reduction of the posterior gonadal arm in monodelphic species or in change in vulva position).
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Mol Cell Neurosci,
1997]
The Notch gene encodes a cell surface protein that regulates cell fate choices in vertebrates and invertebrates. Given the wide variety of cell types influenced by Notch, it would seem that the signal relayed through Notch activation is not an instructive one per se. Rather, Notch signaling is thought to influence the cell's ability to respond to instructive signals responsible for specific cell fates. Expression and functional studies of Notch support this idea; however, the possibility of additional functions for Notch cannot be excluded. Much of what we know about the Notch signaling pathway comes from studies with Drosophila Notch and the Caenorhabditis elegans Notch-related genes
lin-12 and
glp-1. With the isolation of multiple vertebrate Notch genes we are beginning to understand and define Notch signaling in vertebrates as well. A number of excellent reviews have been published summarizing the current status of Notch/LIN-12/GLP-1 signaling in Drosophila and C. elegans, as well as recent findings with the vertebrate counterparts. Here I review the structure of the various Notch proteins and their putative ligands, and discuss possible interactions between Notch, its ligands, and other cellular components that affect Notch signal transduction. A role for Notch signaling during normal development and in disease processes is discussed in an accompanying review by T. Gridley (1997, Mol. Cell. Neurosci. 9: 103-108).