Roberts SB et al. (1985) International C. elegans Meeting "genomic organization and sequence analysis of C elegans histone genes."

Childs G, Roberts SB, Saltzberg L, Emmons SW, Sanicola M

[International C. elegans Meeting, 1985]

Yuen-Yi Tseng et al. (2007) International Worm Meeting "Caenorhabditis elegans expresses a functional ArsA ATPase."

Vivian Liao, Chan-Wei Yu, Jui-Tung Liu, Yuen-Yi Tseng

[International Worm Meeting, 2007]

As arsenic is the most prevalent environmental toxin, it is imperative for us to understand the mechanisms of metalloid detoxification. In prokaryotes, arsenic detoxification is accomplished by chromosomal and plasmid-borne operon-encoded efflux systems. The bacterial ArsA ATPase is the catalytic component of an oxyanion pump that is responsible for resistance to arsenite (As(III)) and antimonite (Sb(III)). Herein, we describe the identification of a Caenorhabditis elegans homologue (asna-1) that encodes the ATPase component of the Escherichia coli As(III) and Sb(III) transporter. We have evaluated the responses of wild-type and asna-1 mutant nematodes to various metal ions and found that asna-1 mutant nematodes are more sensitive to As(III) and Sb(III) toxicity than that of wild-type animals. These results provide evidence that ASNA-1 is required for C. elegans'' defense against As(III) and Sb(III) toxicity. A purified maltose-binding protein (MBP)- ASNA-1 fusion protein was biochemically characterized, and its properties were compared with those of ArsAs. ATPase activity of the ASNA-1 protein was dependent on the presence of As(III) or Sb(III). As(III) stimulated ATPase activity by 2 ± 0.2 (SEM) fold, while Sb(III) stimulated it by 4.6 ± 0.15 (SEM) fold. The results indicate that As(III)- and Sb(III)-stimulated ArsA ATPase activities are not restricted to bacteria but extend to animals by demonstrating that the asna-1 gene of the nematode, C. elegans, encodes a functional ArsA ATPase whose activity is stimulated by As(III) and Sb(III) and which is critical for As(III) and Sb(III) tolerance in the intact organism.

M Tijsterman et al. (1999) International C. elegans Meeting "A genetic approach to identify the molecular target of SB-204269 in Caenorhabditis elegans"

M Tijsterman, GP Livi, J Ahringer, RH Plasterk, S Rastan, H Herdon

[International C. elegans Meeting, 1999]

The compound SB-204269 shows potent anticonvulsant activity in a range of animal seizure models without any neurological or cardiovasular side-effects 1 . A stereospecific binding site has been identified in the rat brain 2 but the molecular nature of this unique binding site remains to be elucidated. We have started to use the strength of C. elegans genetics in an attempt to identify the molecular target of SB-204269. Exposure of mothers to SB-204269 (micromolar range) results in embryonic lethality in this organism whereas its enantiomer SB-204268 does not. A C. elegans strain with a general increased sensitivity to drugs ( pgp-1; pgp-3; mrp-1 ) are also more sensitive to SB-204269 than Bristol N2 and the obtained level of killing allows a large-scale selection for mutants that have gained resistance specifically to the compound. Besides the use of EMS as a source to introduce mutations into the C. elegans genome we crossed a mutator allele ( mut-7 ) into this genetic background to allow a more easy detection of the causal mutation via a transposon display experiment. Both EMS- and "mutator"-screens are currently ongoing. 1 Upton et al. (1997) Br. J. Pharmacol., 121, 1679-1686 2 Herdon et al. (1997) Br. J. Pharmacol. 121, 1687-1691

Sanicola M et al. (1987) International C. elegans Meeting "molecular characterization of the C elegans histone gene family."

Emmons SW, Sanicola M, Roberts SB, Childs G

[International C. elegans Meeting, 1987]

Sanicola M et al. (1985) International C. elegans Meeting "expression of the C elegans histone gene family."

Childs G, Roberts SB, Emmons SW, Sanicola M

[International C. elegans Meeting, 1985]

Emmons SW et al. (1983) International C. elegans Meeting "mutations in Bergerac induced by heat shock."

Emmons SW, Sanicola M, Rubinfeld BZ, Roberts SB, Katzenberg D

[International C. elegans Meeting, 1983]

Carta L (1998) East Coast Worm Meeting "TOXICITY OF 4 SERRATIA MARCESCENS BACTERIAL STRAINS TOWARD C. ELGANS N2, PGP-3 AND OTHER NEMATODES IS INVERSELY RELATED TO PIGMENT"

Carta L

[East Coast Worm Meeting, 1998]

We are testing a number of biocontrol bacteria (eg. Burkholderia, Pseudomonas and Stenotrophomonas) for toxicity to bacterial feeding nematodes including C. elegans N2 and pgp-3. Serratia marcescens in particular had a measurable effect on number of eggs over 24 hours and relative motility in microtiter wells. Serratia marcescens strains with increasing amounts of red pigmentation (BF1-5@ (albino), D1, N4-5, NIMA) were tested for relative motility to C. elegans N2, pgp3, Oscheius myriophila DF5020, Panagrellus redivivus PS 1163, Mesorhabditis sp. PS1170 and Zeldia punctata PS 1153. Toxicity directly increases with decreasing amount of pigment in Caenorhabditis, Oscheius and Panagrellus. The order of relative toxicity is reversed for the 2 highly pigmented strains and the 2 least pigmented strains (2143 vs. 1234) in Mesorhabditis and Zeldia. These nematodes are phylogenetically distant from C. elegans. Bacterial strains were provided by Phyllis Martin and Dan Roberts, USDA.

Douglas, C.D. et al. (2011) International Worm Meeting "The effects of nickel toxicity upon survival, growth, and reproduction in nematodes."

Ingersoll, C.G., Besser, J.M., Douglas, C.D., Rudel, D.

[International Worm Meeting, 2011]

Nickel is one of the most prevalent heavy metal contaminants in the dust floating in the air we breath, in soils, and in many waterways. Contamination continues to increase largely due to human activities like mining, manufacturing, and waste management. Ni2+ is a carcinogen to plants and animals, and a major concern for the health and safety both of humans and food crops. In addition to mutagenesis and cancer, nickel exposure leads to a variety of other deleterious health conditions. In collaboration with the United States Geological Survey, an assay to evaluate the effects of substrate bound nickel and soluble nickel on survival, growth, and fecundity using C. elegans and Pristionchus pacificus has been developed. Synchronized L1 (C. elegans) or J2 (P. pacificus) larvae were added to sediment and water samples in twelve-well tissue culture plates with a defined amount of freshly killed bacteria as a food source. Animals were grown for 96 hours at 20degC and harvested. Harvested animals were assayed for survival, growth, and fertility. Growth in eight sediment-types collected at discrete uncontaminated sites along the Missouri/Mississippi river basin suggests that both nematodes grow well in organic based sediments and less well in more sandy/inorganic based sediments. Growth in sediments spiked with increasing amounts of environmentally relevant levels of sediment-bound nickel showed that C. elegans was highly sensitive to nickel in the environment of the sediment. Treatment was lethal prior to adulthood. Growth in nickel spiked liquid media with freshly killed food and cholesterol, i.e. hard H20 pH 7.5, distilled (DI) H20, SB Media (hard H20), and SB Media (DI H20), showed that C. elegans has a strong tolerance for environmentally relevant levels of soluble nickel. Adult survivors of nickel treatments showed no significant effects on adult length/width measurements or the presence of fertilized eggs in the uterus. As nickel has other known cell stress effects, we will also assay total germline apoptosis as an measure of DNA damage.

Chan-Wei Yu et al. (2007) International Worm Meeting "Characterization and regulation of the C. elegans GCS-1 by arsenite."

Chan-Wei Yu, Vivian Liao

[International Worm Meeting, 2007]

Arsenic is a potent toxin and carcinogen. We previously demonstrated that GCS-1 is essential for the synthesis of intracellular GSH in C. elegans and consequently that the intracellular GSH status plays a critical role in protection of C. elegans from arsenic-induced oxidative stress (Yu and Liao, 2005). Herein we investigate the regulation of GCS-1 in response to As(III). Our results showed that As(III) caused a concentration-dependent increase in the GSH levels up to a concentration of 10 <font face=symbol>m</font>M. Real-time RT-PCR analysis shows that gcs-1 mRNA transcript is most abundant in L1, L2 and adult stages. Whereas GCS-1 mRNA at L1 and dauer stages exhibited higher induction ratio after 1 h of As(III) exposure. Moreover, we observed that the increase in GCS-1 mRNA expression level caused by As(III) shows dose-dependence fashion, in parallel with the increase in the GSH level. RNAi feeding assay showed that worms that were fed GCS-1 dsRNA and were grown in the presence of 0.25 mM As(III) were obviously small and development arrest. Transcription of gcs-1 was observed in the pharynx, ASI chemosensory neurons, and intestine of post-embryonic C. elegans and upon exposure to As(III), As(V), or Sb(III), the intestinal expression increases dramatically; whereas Cd(II) induced significant expression in the pharynx. Together, our results indicated that GCS-1 is developmentally regulated and it plays a critical role for the protection of C. elegans against arsenic-induced oxidative stress.

McKnight S et al. (1998) West Coast Worm Meeting "PRELIMINARY STUDIES OF A CANDIDATE REGULATOR OF AMOEBOID CELL MOTILITY"

McKnight S, Dill K, Ward S

[West Coast Worm Meeting, 1998]

One of the many distinctive features of C. elegans spermatozoa is their amoeboid motility system. These cells extend a dynamic pseudopod whose movements are proposed to be fueled by polymerization of filaments of the Major Sperm Protein under the plasma membrane. The major sperm protein (MSP) comprises 15% of the total protein in these cells and is the main component of the spermatozoon cytoskeleton. The in vitro reconstruction of the MSP-based motility system of the nematode Ascaris suum, by Tom Roberts and colleagues, demonstrated that the polymerization of MSP filaments could move vesicles derived from the plasma membrane; but, this polymerization is dependent on the presence of a phosphorylated protein associated with the cytoplasmic side of the vesicles. Recently, database searching identified a gene in C. elegans, Aplysia, humans, yeast, plants and several other organisms, which bears homology to the MSP genes. Curiously, the Aplysia gene, VAP-33, is involved in synaptic vesicle release. In C. elegans, the expression of this homolog's transcript is not restricted to sperm. The C. elegans gene was designated MPL-1 (for Major Sperm Protein Like), and appears to be a longer more ancient form of the MSP gene. The N-terminal portion of the protein shares homology with MSP, while the C-terminal portion contains strongly predicted transmembrane and coiled-coil domains. Despite its expression in other tissues besides the testis, the overall topology of MPL-1 and its homology with MSP qualify MPL-1 as a candidate for a protein which regulates cell motility by nucleating MSP filament assembly at the plasma membrane. To investigate the possibility that MPL-1 nucleates MSP filament assembly, we have tested the MPL-1 gene product for a physical interaction with MSP in the Yeast Two-Hybrid system. Currently, we have suggestive evidence that MPL-1 interacts with MSP in vivo.