Adams A (1999) Worm Breeder's Gazette "Philadelphia's Northeast High School Worm Project experiment on the space shuttle Discovery"

Adams A

[Worm Breeder's Gazette, 1999]

We recently had a chance to do something only a handful of people have ever done: send an experiment up into space. We sent up an 'experimental' group of dauer larvae on the space shuttle Discovery's ten-day mission. ITA of Exton, PA, granted us a very small space on the shuttle. So we decided on the relatively small C. elegans. We figured since John Glenn was going up into space to see the effects on him, we'd do a similar study. We wanted to see if the conditions of space had any effect on the C. elegans normal 18-24 day life span. With every science experiment there is a control group and an experimental group. The control group of about 1000 worms stayed in Philadelphia at Northeast High School the other 1000 worms were blasted off into orbit October 29, 1998.

Zahreddine Fahs, Hala et al. (2021) International Worm Meeting "Multi-species nematode screening uncovers a new broad-spectrum class of anthelmintic compounds targeting mitochondrial lipid metabolism"

Gopinadhan, Suma, Refai, Fathima, White, Robert, Pearson, Yanthe, Kremb, Stephan, Butterfoss, Glenn, Gunsalus, Kristin C., Zahreddine Fahs, Hala, Xie, Xin, Cipriani, Patricia, Page, Anthony, Piano, Fabio

[International Worm Meeting, 2021]

Parasitic worms infect more than 1.5 billion people and cause significant losses in livestock and crops. New anthelmintic drugs are urgently needed, as resistance to the existing drugs is emerging. We built a high-throughput (HTP) and high-content robotic screening platform to identify bioactive small molecules and their molecular targets, focusing on novel disease therapeutics and broad spectrum anthelmintics. The platform is capable of screening compound collections and genetic libraries in model organisms and mammalian cells in a fully integrated manner. To find novel anthelmintics we screened a ~2300 compound library containing most of the FDA-approved approved drugs, plus natural products and bioactive compounds for broad spectrum toxic effects on two distantly related free living nematodes C. elegans and P. pacificus as model animals while having low toxicity on human cell lines. The screen confirmed the effects of most known anthelmintics on these nematode models. Additionally, among a set of new compounds, we found six natural lipid molecules that exhibit broad-spectrum anthelmintic activity. These novel compounds kill C. elegans and P. pacificus when applied at various developmental stages, including the dauer and embryonic stages, in a dose-dependent manner. Importantly, these compounds cause mortality in all three veterinary parasite species we tested: the hookworm Haemonchus contortus (ruminants), Teladorsagia circumcincta (sheep and goat) and Heligmosomoides polygyrus (rodents). Further characterization of their mode of action using C. elegans revealed defects associated with mitochondrial function and lipid metabolism. The lethality phenotype in C. elegans is partially rescued by knocking down the enzymes acs-2, cpt-4, dif-1 and cpt-2, which facilitates mitochondrial lipid transfer, while drug inhibitors of CPT1 and CPT2 enhance the phenotype, suggesting that these compounds perturb specifically fatty acid oxidation in nematodes. These compounds constitute a new class of broad-spectrum anthelmintics targeting lipid metabolism.

Heimbucher, Thomas W et al. (2011) International Worm Meeting "A Biochemical Approach for the Identification of new DAF-16 Binding-partners."

Andrew, Dillin, Heimbucher, Thomas W, Bryan, Fonslow, Jonathan, Yates

[International Worm Meeting, 2011]

The FoxO transcription factor DAF-16 regulates a wide range of organismal functions: it is involved in C. elegans development and reproduction, in stress response and life span regulation. Association of DAF-16 with diverse binding partners might be crucial for mediating these heterogeneous functions (1-4). To identify DAF-16 regulators we established a biochemical approach for the purification of DAF-16 associated proteins. DAF-16 was fused to various epitop-tags. On the basis of a reporter assay it was analyzed whether the tagged DAF-16 versions were transcriptionally active and a dauer assay was used to test for their physiological activity in worms. A functional tagged DAF-16 variant was used for the generation of transgenic worms. DAF-16 protein complexes were isolated by tandem affinity purification and potential DAF-16 binding partners were identified by tandem mass-spectrometry (MudPIT). In an additional, reporter based screen DAF-16 co-regulators are currently validated and their potential roles in dauer formation, stress resistance and longevity are currently being pursued. We will discuss their identity and potential functions in insulin/IGF-1 signaling. (1): Essers, MA. et al., Science. 2005; 308(5725): 1181-1184 (2): Wolff, S. et al., Cell. 2006; 124(5): 1039-1053 (3): Berdichevsky, A. et al., Cell. 2006; 125(6): 1165-1177 (4): Li, J. et al., PLoS Biol. 2008; 6(9): 1870-1886 This work was supported in part by the Austrian Science Fund (FWF, grant J2734), by a grant from NIH, and by the Glenn Center for Aging Research.

Stormberg, A. I. et al. (2006) "Use of Transgenic Caenorhabditis elegans (HS-1 line) for Detection of Heavy Metals in Aquatic Media"

Glenn, T., Humphries, S., Williams, P. L., Stormberg, A. I., Barnes, J. M.

[2006]

Use of Transgenic Caenorhabditis elegans (HS-1 line) for Detection of Heavy Metals in Aquatic Media Stormberg A. I.1, Barnes, J. M.1, Humphries S.2, Glenn T.3, and Williams P. L.4. Detection and quantification of contaminants in water and soil continues to be of paramount importance in all areas of human activities, especially in those where waste is generated, treated and disposed-of. Bioassays have become the standard method for monitoring hazardous waste, and numerous approaches exist in the literature describing the use of invertebrates as sentinels for environmental health. In this study we describe a rapid, inexpensive assay of contaminant bioavailability. We used a transgenic line (HS-1) of the nematode Caenorhabditis elegans to develop dose-response assays for aqueous solutions of cadmium, zinc, mercury, lead, and nickel. This transgenic line carries an integrated promoter from the C. elegans metallothionein-2 gene (mtl-2), which controls the transcription of the green fluorescence protein (GFP). This line provides a very fast and sensitive assay for heavy metal exposure since the response can be directly detected with a fluorimeter and does not require additional reagents or co-factors. At high metal concentrations, the system requires only 4 hours of exposure and at lower levels, up to 24 hours.. This study shows that there is a positive correlation between the concentration of the specific metal used in the assay and the fluorescent emission. Work in progress will focus on testing the transgenic line under a mix of metals. In addition we are interested in determining if there is a linear correlation between GFP emission and metal concentration. The ultimate goal is to design a qualitative indicator system for the presence of heavy metals in aquatic samples.

Stormberg A. I. et al. (2006) European Worm Meeting "Use of Transgenic Caenorhabditis elegans (HS-1 line) for Detection of Heavy Metals in Aquatic Media"

Barnes J. M., Stormberg A. I., Glenn T., Williams P. L., Humphries S.

[European Worm Meeting, 2006]

Use of Transgenic Caenorhabditis elegans (HS-1 line) for Detection of Heavy Metals in Aquatic Media Stormberg A. I.1, Barnes, J. M.1, Humphries S.2, Glenn T.3, and Williams P. L.4. Detection and quantification of contaminants in water and soil continues to be of paramount importance in all areas of human activities, especially in those where waste is generated, treated and disposed-of. Bioassays have become the standard method for monitoring hazardous waste, and numerous approaches exist in the literature describing the use of invertebrates as sentinels for environmental health. In this study we describe a rapid, inexpensive assay of contaminant bioavailability. We used a transgenic line (HS-1) of the nematode Caenorhabditis elegans to develop dose-response assays for aqueous solutions of cadmium, zinc, mercury, lead, and nickel. This transgenic line carries an integrated promoter from the C. elegans metallothionein-2 gene (mtl-2), which controls the transcription of the green fluorescence protein (GFP). This line provides a very fast and sensitive assay for heavy metal exposure since the response can be directly detected with a fluorimeter and does not require additional reagents or co-factors. At high metal concentrations, the system requires only 4 hours of exposure and at lower levels, up to 24 hours.. This study shows that there is a positive correlation between the concentration of the specific metal used in the assay and the fluorescent emission. Work in progress will focus on testing the transgenic line under a mix of metals. In addition we are interested in determining if there is a linear correlation between GFP emission and metal concentration. The ultimate goal is to design a qualitative indicator system for the presence of heavy metals in aquatic samples.