Matthews LR et al. (1994) Worm Breeder's Gazette "A Potential C. elegans E2F Homolog: Is it zyg-9?"

Galas S, Matthews LR

[Worm Breeder's Gazette, 1994]

A potential C. elegans E2F homolog: Is it zyg-9? Lisa Matthews and Simon Galas, CRBM, CNRS Montpellier, France

Berger S et al. (2018) Lab Chip "Correction: Long-term C. elegans immobilization enables high resolution developmental studies in vivo."

Aegerter-Wilmsen T, DeMello A, Berger S, Casadevall I Solvas X, Hengartner M, Hajnal A, Lattmann E

[Lab Chip, 2018]

Correction for 'Long-term C. elegans immobilization enables high resolution developmental studies in vivo' by Simon Berger et al., Lab Chip, 2018, 18, 1359-1368.

Charlesworth AG et al. (2019) Cell "Next-Gen Learning: The C.elegans Approach."

Claycomb JM, Seroussi U, Charlesworth AG

[Cell, 2019]

In this issue, Moore etal. and Posner etal., provide evidence for how the activity of the nervous system in C.elegans results in gene expression changes in the germline to pass on parental experiences and learned behavior to their progeny.

Moore RS et al. (2021) STAR Protoc "Protocol for transgenerational learned pathogen avoidance behavior assays in Caenorhabditis elegans."

Moore RS, Murphy CT, Kaletsky R

[STAR Protoc, 2021]

Animal experiences, including learned behaviors, can be passed down to several generations of progeny in a phenomenon known as transgenerational epigenetic inheritance. Yet, little is known regarding the molecular mechanisms regulating physiologically relevant transgenerational memories. Here, we present a method for <i>Caenorhabditis elegans</i> in which worms learn to avoid the pathogen <i>Pseudomonas aeruginosa</i> (PA14). Unlike previous protocols, this training paradigm, either using PA14 lawns or through exposure to a PA14 small RNA (P11), induces memory in four generations of progeny. For complete details on the use and execution of this protocol, please refer to Moore etal. (2019) and Kaletsky etal. (2020).

Vazquez-Prada, Mireya et al. (2021) International Worm Meeting "The microbiome-muscle connection: Native microbiota affect muscle ageing and motility"

Scanlon, Daniel, Karamalegos, Antonis, Dennis, Nathan, Moore, Simon, Aubrey, Liam, Vazquez-Prada, Mireya, Ezcurra, Marina, Xue, Wei-Feng

[International Worm Meeting, 2021]

Large-scale human metagenomic sequencing has identified associations between gut microbiome composition and host physiology, including immunity, nervous system function, and ageing. New findings in humans and model organisms suggest that the gut microbiome affects healthy ageing, and that the microbiome could be used to develop interventions to improve the way we age, but underlying mechanisms are not understood. To define host-microbiome interactions affecting ageing we have established a new model system consisting of the nematode C. elegans combined with an experimental microbiome of 11 bacterial isolates representing the most abundant genera of C. elegans in the wild. Cultivation with the experimental microbiome preserves age-related motility, an effect that requires components of the p38 MAP kinase pathway, including nsy-1 and pmk-1. The experimental microbiome also induces mitochondrial fragmentation in body-wall muscle in a non-pmk-1 dependent manner, suggesting multiple routes of communication by which the experimental microbiome may modulate age-related motility. In a transgenic proteotoxicity model expressing human AB42 in muscle, age-associated paralysis is suppressed by the experimental microbiome. Cell-free supernatant from the experimental microbiome suppresses paralysis and reduces AB42 aggregation in vitro, suggesting secretion of microbial bioactive compounds capable of abrogating AB42-associated toxicity. Together these findings show that molecular host-microbiome interactions modulate muscle function, mitochondrial dynamics and proteostasis during ageing to delay age-related decline in motility.

Davies JB (1993) Ann Trop Med Parasitol "Description of a computer model of forest onchocerciasis transmission and its application to field scenarios of vector control and chemotherapy."

Davies JB

[Ann Trop Med Parasitol, 1993]

This paper describes a computer simulation model for onchocerciasis (SIMON). Using epidemiological and entomological data from a specific hyperendemic village in the forest area of Sierra Leone, the model is used to examine the effect of vector and chemotherapeutic control strategies, both separately and in combination, as well as the risk to an uninfected population caused by immigrant, infected Simulium damnosum and humans. The model suggests that, in this village, the human population of about 420 requires an average annual input of about 200 mature fecund, female Onchocerca volvulus per year to maintain a skin-snip prevalence of just under 70%. SIMON also predicts that 99% effective vector control would lead to eradication of all adult worms in 18 years, and that abandoning control before 14 years could lead to recrudescence. Chemotherapy with ivermectin at six-month intervals reaching 90% of eligible persons (effective 66%) might take 29 years to achieve eradication because of continuing transmission, particularly in the early years, but it would probably be possible to abandon treatments after 18 years because the residual worm population would no longer be self-sustaining. Combined ivermectin and vector control, both at reduced levels, could be as effective as 99% vector control. Immigrant infected flies are likely to pose a greater threat to an uninfected human population than small numbers of infected persons. The model suggests that, at levels of infection undetectable by skin-snip, the parasite could linger in the human population for 30 or more years sustained by sporadic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Reboul J et al. (2001) Nat Genet "Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans."

Doucette-Stamm L, Lamesch PE, Reboul J, Temple GF, Hartley JL, Brasch MA, Hill DE, Vaglio P, Thierry-Mieg N, Shin-i T, Lee H, Moore T, Vandenhaute J, Kohara Y, Vidal M, Jackson C, Thierry-Mieg J, Tzellas N, Thierry-Mieg D, Hitti J

[Nat Genet, 2001]

The genome sequences of Caenorhabditis elegans, Drosophila melanogaster and Arabidopsis thaliana have been predicted to contain 19,000, 13,600 and 25,500 genes, respectively. Before this information can be fully used for evolutionary and functional studies, several issues need to be addressed. First, the gene number estimates obtained in silico and not yet supported by any experimental data need to be verified. For example, it seems biologically paradoxical that C. elegans would have 50% more genes than Drosophilia. Second, intron/exon predictions need to be tested experimentally. Third, complete sets of open reading frames (ORFs), or "ORFeomes," need to be cloned into various expression vectors. To address these issues simultaneously, we have designed and applied to C. elegans the following strategy. Predicted ORFs are amplified by PCR from a highly representative cDNA library using ORF-specific primers, cloned by Gateway recombination cloning and then sequenced to generate ORF sequence tags (OSTs) as a way to verify identity and splicing. In a sample (n=1,222) of the nearly 10,000 genes predicted ab initio (that is, for which no expressed sequence tag (EST) is available so far), at least 70% were verified by OSTs. We also observed that 27% of these experimentally confirmed genes have a structure different from that predicted by GeneFinder. We now have experimental evidence that supports the existence of at least 17,300 genes in C. elegans. Hence we suggest that gene counts based primarily on ESTs may underestimate the number of genes in human and in other organisms.AD - Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.FAU - Reboul, JAU - Reboul JFAU - Vaglio, PAU - Vaglio PFAU - Tzellas, NAU - Tzellas NFAU - Thierry-Mieg, NAU - Thierry-Mieg NFAU - Moore, TAU - Moore TFAU - Jackson, CAU - Jackson CFAU - Shin-i, TAU - Shin-i TFAU - Kohara, YAU - Kohara YFAU - Thierry-Mieg, DAU - Thierry-Mieg DFAU - Thierry-Mieg, JAU - Thierry-Mieg JFAU - Lee, HAU - Lee HFAU - Hitti, JAU - Hitti JFAU - Doucette-Stamm, LAU - Doucette-Stamm LFAU - Hartley, J LAU - Hartley JLFAU - Temple, G FAU - Temple GFFAU - Brasch, M AAU - Brasch MAFAU - Vandenhaute, JAU - Vandenhaute JFAU - Lamesch, P EAU - Lamesch PEFAU - Hill, D EAU - Hill DEFAU - Vidal, MAU - Vidal MLA - engID - R21 CA81658 A 01/CA/NCIID - RO1 HG01715-01/HG/NHGRIPT - Journal ArticleCY - United StatesTA - Nat GenetJID - 9216904SB - IM

Lars Nilsson et al. (2006) European Worm Meeting "C. elegans NUM-1 Modulates Endocytosis by Targeting the TAT-1 Phospholipid Flippase"

Lars Nilsson, Simon Tuck

[European Worm Meeting, 2006]

Lars Nilsson and Simon Tuck. We have previously reported that C. elegans NUM-1 modulates both endocytosis and the activity of LIN-12, a receptor that mediates a number of cell fate specification events in the worm. In order to understand better how NUM-1 functions, we carried out a yeast 2-hybrid screen for interacting proteins. One clone we isolated encodes TAT-1, a transmembrane P-type ATPase. Work in S. cerevisiae has shown that these proteins function as so-called inward phospholipid flippases to concentrate specific phospholipids to the cytosolic leaflet of biological membranes. They are known to be associated with endosomes and to be required for correct vesicle trafficking. We have found that TAT-1 is expressed in tissues in which NUM-1 functions. Mapping of the regions required for binding revealed that the PTB domain of NUM-1 associates with an NXXF motif at the C-terminus of TAT-1. RNAi experiments show that tat-1 affects membrane trafficking in C. elegans. Our results suggest that NUM-1 functions in the worm by modulating TAT-1 activity.

Ouyang YB et al. (1998) J Biol Chem "Molecular cloning and expression of human and mouse tyrosylprotein sulfotransferase-2 and a tyrosylprotein sulfotransferase homologue in Caenorhabditis elegans."

Moore KL, Ouyang YB

[J Biol Chem, 1998]

Tyrosine O-sulfation, a common post-translational modification in eukaryotes, is mediated by Golgi enzymes that catalyze the transfer of the sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate to tyrosine residues in polypeptides. We recently isolated cDNAs encoding human and mouse tyrosylprotein sulfotransferase-1 (Ouyang, Y. B., Lane, W. S., and Moore, K. L. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 2896-2901). Here we report the isolation of cDNAs encoding a second tyrosylprotein sulfotransferase (TPST), designated TPST-2. The human and mouse TPST-2 cDNAs predict type II transmembrane proteins of 377 and 376 amino acid residues, respectively. The cDNAs encode functional N-glycosylated enzymes when expressed in mammalian cells. In addition, preliminary analysis indicates that TPST-1 and TPST-2 have distinct specificities toward peptide substrates. The human TPST-2 gene is on chromosome 22q12.1, and the mouse gene is in the central region of chromosome 5. We have also identified a cDNA that encodes a TPST in the nematode Caenorhabditis elegans that maps to the right arm of chromosome III. Thus, we have identified two new members of a class of membrane-bound sulfotransferases that catalyze tyrosine O-sulfation. These enzymes may catalyze tyrosine O-sulfation of a variety of protein substrates involved in diverse physiologic functions.

JJ Yochem (1999) International C. elegans Meeting "Mutations that confer aspects of the molting defects seen with lrp-1 mutations or sterol starvation"

JJ Yochem

[International C. elegans Meeting, 1999]

Mutations that produce larvae that are completely stuck in old cuticle, that have rings of unshed cuticle that constrict regions of the body, or that have attached to the tail a train of old cuticle will be described. Such larvae can be detected with a dissecting microscope, permitting a semi-clonal screen. The search for such mutations was begun because a failure to complete molting is an aspect of the phenotype conferred by loss-of-function mutations in lrp-1 , the product of which resembles mammalian gp330/megalin, a large member of the LDL receptor family of proteins [Yochem et al., Development 126, 597 (1999)]. It is hoped that new mutations will reveal genes whose products are required for the same process as LRP-1. The mutations also have the potential for increasing our understanding of molting, a process that has not been much studied genetically in nematodes. To date, mutations have defined eight candidate genes. Of particular note are mlt-3(sv8) and mlt-7(sv16) , both of which closely resemble the lrp-1 mutant phenotype. Thanks to Simon Tuck, Min Han, and Bob Herman.