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The New York Times,
1997]
His tall figure bent over a computer screen in his laboratory at the Massachusetts General Hospital, Dr. Gary Ruvkun rummages through a distant genetic data base for matches to a gene he believes is involved in diabetes. ?You learn how to read these as they are ratcheting by,? he says, while lines of data streak up his screen. ?I think MTV is good training.?
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Traffic,
2002]
t is almost 40 years since Sydney Brenner introduced Caenorhabditis elegans as a model genetic system. During that time mutants with defects in intracellular trafficking have been identified in a diverse range of screens for abnormalities. This should, of course, come as no surprise as it is hard to imagine any biological process in which the regulated movement of vesicles within the cells is not critical at some step. Almost all of these genes have mammalian homologs, and yet the role of many of these homologs has not been investigated. Perhaps the protein that regulates your favorite trafficking step has already been identified in C elegans? Here I provide a brief overview of those trafficking mutants identified in C elegans and where you can read more about them.
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Science,
1997]
When I began working on the small nematode Caenorhabditis elegans in the early '70s, not long after Sydney Brenner had chosen it as a model organism for studying animal development and behavior, one could read most of the essentials then published about the creature in an afternoon. As more people joined the worm community and wrote papers that demanded attention, newcomers and interested spectators faced an ever bigger job trying to familiarize themselves with the field. In 1988, a book, The Nematode Caenorhabditis elegans, came to the rescue. "Worm I" reviewed the worm's genome, anatomy, embryology, sex determination, muscle development, and behavior, among other things. Appendixes contained a list of all 959 somatic hermaphrodite cells and their lineages, a list of 774 mapped genes and mutant phenotypes, and a compilation of laboratory methods. "Worm I" has aged gracefully but is irrevocably stuck at 1988. Enter "Worm II".
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J Cell Sci,
2004]
Junctional adhesion molecules (JAMs) are members of an immunoglobulin subfamily expressed by leukocytes and platelets as well as by epithelial and endothelial cells, in which they localize to cell-cell contacts and are specifically enriched at tight junctions. The recent identification of extracellular ligands and intracellular binding proteins for JAMs suggests two functions for JAMs. JAMs associate through their extracellular domains with the leukocyte beta2 integrins LFA-1 and Mac-1 as well as with the beta1 integrin alpha4beta1. All three integrins are involved in the regulation of leukocyte-endothelial cell interactions. Through their cytoplasmic domains, JAMs directly associate with various tight junction-associated proteins including ZO-1, AF-6, MUPP1 and the cell polarity protein PAR-3. PAR-3 is part of a ternary protein complex that contains PAR-3, atypical protein kinase C and PAR-6. This complex is highly conserved through evolution and is involved in the regulation of cell polarity in organisms from Caenorhabditis elegans and Drosophila to vertebrates. These findings point to dual functions for JAMs: they appear to regulate both leukocyte/platelet/endothelial cell interactions in the immune system and tight junction formation in epithelial and endothelial cells during the acquisition of cell polarity.
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Biotechnol Adv,
2016]
Billions of people and animals are infected with parasitic worms (helminths). Many of these worms cause diseases that have a major socioeconomic impact worldwide, and are challenging to control because existing treatment methods are often inadequate. There is, therefore, a need to work toward developing new intervention methods, built on a sound understanding of parasitic worms at molecular level, the relationships that they have with their animal hosts, and/or the diseases that they cause. Decoding the genomes and transcriptomes of these parasites brings us a step closer to this goal. The key focus of this article is to critically review and discuss bioinformatic tools used for the assembly and annotation of these genomes and transcriptomes, as well as various post-genomic analyses of transcription profiles, biological pathways, synteny, phylogeny, biogeography and the prediction and prioritisation of drug target candidates. Bioinformatic pipelines implemented and established recently provide practical and efficient tools for the assembly and annotation of genomes of parasitic worms, and will be applicable to a wide range of other parasites and eukaryotic organisms. Future research will need to assess the utility of long-read sequence data sets for enhanced genomic assemblies, and develop improved algorithms for gene prediction and post-genomic analyses, to enable comprehensive systems biology explorations of parasitic organisms.
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Arch Toxicol,
2017]
In view of increased life expectancy the risk for disturbed integrity of genetic information increases. This inevitably holds the implication for higher incidence of age-related diseases leading to considerable cost increase in health care systems. To develop preventive strategies it is crucial to evaluate external and internal noxae as possible threats to our DNA. Especially the interplay of DNA damage response (DDR) and DNA repair (DR) mechanisms needs further deciphering. Moreover, there is a distinct need for alternative in vivo test systems for basic research and also risk assessment in toxicology. Especially the evaluation of combinational toxicity of environmentally present genotoxins and adverse effects of clinically used DNA damaging anticancer drugs is a major challenge for modern toxicology. This review focuses on the applicability of Caenorhabditis elegans as a model organism to unravel and tackle scientific questions related to the biological consequences of genotoxin exposure and highlights methods for studying DDR and DR. In this regard large-scale in vivo screens of mixtures of chemicals and extensive parallel sequencing are highlighted as unique advantages of C. elegans. In addition, concise information regarding evolutionary conserved molecular mechanisms of the DDR and DR as well as currently available data obtained from the use of prototypical genotoxins and preferential read-outs of genotoxin testing are discussed. The use of established protocols, which are already available in the community, is encouraged to facilitate and further improve the implementation of C. elegans as a powerful genetic model system in genetic toxicology and biomedicine.