Wender, Nora et al. (2011) International Worm Meeting "Analysis of cellular toxicity mechanisms of alpha-synuclein in C. elegans."

Wender, Nora, Hegermann, Jan, Eimer, Stefan

[International Worm Meeting, 2011]

Aggregation of a-synuclein (aS) in Lewy bodies is one of the pathological hallmarks of Parkinson's disease (PD). Mutations in aS as well as increased aS expression levels have been associated with PD. As the PD mutants of aS are more prone to forming fibrillar aggregates, these fibrils were initially considered to be causing toxicity. However, in different model systems no clear correlation between toxicity and fibril formation was found. This indicates that small oligomeric precursors rather than fibrils might be the toxic species. In order to investigate which form of aS is causing toxicity, we were making use of a designed variant of aS that stops at the stage of soluble oligomers. This variant is called TP aS (triple proline aS) as it was derived from wt aS by introduction of three proline residues. In vitro NMR studies as well as in vivo analysis of the aggregation of aS variants tagged with YFP in C. elegans muscle cells confirmed that the occurrence of aS fibrils was strongly reduced in TP aS. Next we were assessing toxicity of TP aS in comparison to wt aS as well as PD mutants of aS by investigation of neurite degeneration and impairment of dopamine-associated behavior upon expression of different aS variants in C. elegans dopaminergic neurons. We found that TP is the most toxic aS variant, exhibiting the most severe effects on dopaminergic neuron morphology and function. This suggests that indeed the small oligomers rather than aS fibrils are causing toxicity. So far, the cellular function of aS and the mechanisms causing toxicity remain unclear. It is known that aS binds to intracellular membranes including the mitochondrial membrane. Furthermore, mitochondrial impairment upon expression of wt and mutant aS was reported. Recently it has been reported that several PD-associated genes play a role in mitochondrial dynamics and that loss of function or overexpression leads to morphological changes in the mitochondrial network. Therefore we aimed in understanding how expression of different variants of aS affects mitochondrial dynamics. Thus we were analyzing mitochondrial morphology and distribution by Electron Microscopy as well as Spinning Disk Microscopy. We found that expression of aS in C. elegans muscles and neurons leads to mitochondrial fragmentation and severe changes in mitochondrial morphology. Remarkably, similar changes could be observed in aged worms not expressing aS. It is therefore tempting to suggest that increased expression levels of aS accelerate mitochondrial aging.

Cain, S. et al. (2019) International Worm Meeting "Genome Browsing at WormBase."

Gao, S., Grove, C., Nuin, P., Stein, L., Harris, T., Wright, A., Cain, S.

[International Worm Meeting, 2019]

Here we present recent updates to the genome browser at WormBase, JBrowse. Since it's introduction three years ago, JBrowse's presence in WormBase has grown, as has its functionality. JBrowse updates include the addition of new datasets, display improvements and increased functionality. Dataset changes include the addition of common and rare predicted introns from RNAseq data as well as the ability to add modERN and other public datasets. Visualization changes include improvements to how modENCODE tracks are displayed as well as the addition of new and improved glyphs throughout the app.

Michael Han et al. (2007) International Worm Meeting "WormBase: Comparative Genomics."

Michael Han, Todd Harris, Sheldon McKay

[International Worm Meeting, 2007]

WormBase is the reference database for multiple Caenorhabditae species and provides comprehensive information on comparative Nematode genomics. The comparative genomics data in Wormbase has been extended by including more species, additional methods for comparison and by more regular updates. Data on the new Caenorhabditis briggsae assembly and the draft Caenorhabditis remanei genome has been included as well as the first draft of the Caenorhabditis sp 2801. Additional and updated ortholog predictions like EnsEMBL - Compara, TreeFam and InParanoid, supplemental experimental evidence and tighter integration with EnsEMBL provides a wider range of species for intergenome comparisons as well as a more comprehensive view of currently available data. Pairwise genome alignments from WABA as well as multiple genome alignments using MLAGAN / PECAN can be accessed through the new syntheny viewer in addition to being downloadable as flatfiles from the WormBase FTP-servers.

Queiros, Libania et al. (2021) International Worm Meeting "Evidence for the inclusion of Caenorhabditis elegans in Environmental Risk Assessment routines"

Queiros, Libania, J. M. Goncalves, Fernando, Pereira, Patricia, Pacheco, Mario, Aschner, Michael, L. Pereira, Joana

[International Worm Meeting, 2021]

Caenorhabditis elegans has long been used as a choice for a laboratory model organism, and it has been linked to several discoveries that have led to Nobel Prizes. Although C. elegans' journey as an invaluable model in developmental biology and neurobiology is long, dating to the 1960s, its application in other research fields such as environmental toxicology is more recent. As a well-known experimental organism bearing high sensitivity to different environmental contaminants, and representing important functional levels in soil and aquatic ecosystems, C. elegans has high potential to be extensively integrated within Environmental Risk Assessment (ERA) routines. The major advantages supporting the inclusion of C. elegans in lower tiers of ERA, where a first screening of potential hazardous scenarios to the biota of both environmental compartments is performed, as well as the large array of endpoints that can be tested in this context, are herein presented. In addition, its sensitivity to contaminants such as metals and pesticides, as well as specific strengths and limitations, are compared to other laboratorial model organisms commonly used in ERA, such as Daphnia magna (crustacean) and Eisenia fetida (earthworm). The inclusion of C. elegans in ERA routines is encouraged, since it may provide ecologically relevant insights on the effects of contaminants, thus improving the establishment of appropriate environmental protection benchmarks.

Johnson CJ et al. (1997) International C. elegans Meeting "CHARACTERIZATION OF A STRESS-RESPONSIVE REPORTER TRANSGENE"

Cypser JR, Johnson TE, Link CD, Johnson CJ

[International C. elegans Meeting, 1997]

We have characterized a set of integrated reporter transgenes that are inducible by a variety of physiological stresses. These transgenes are based on a construct employing an hsp-16-2 promoter element and GFP. In addition to a robust response to heat shock, these transgenes express GFP in response to induced reactive oxygen species (ROS) stress, as well as "endogenous" stresses. Specifically, these lines have been observed to express GFP in respone to incubation in juglone (a redox cycling quinone that generates intracellular superoxide), as well as hydrogen peroxide. Experiments examining transgene response to hyperbaric oxygen are currently underway. Expression of these reporter transgenes has also been observed in aging animals (not heat shocked), as well as in transgenic animals co-expressing beta amyloid peptide. As these transgenic lines allow visualization of stress response in living animals, they may be valuable in genetic screens designed to identify mutations that modulate the stress response.

Vivian Hsiu-chuan Liao et al. (2005) International Worm Meeting "gcs-1 confers resistance to arsenic-induced oxidative stress in Caenorhabditis elegans"

Chan-Wei Yu, Vivian Hsiu-chuan Liao

[International Worm Meeting, 2005]

47;-Glutamylcysteine synthetase (47;-GCS) catalyzes the first, rate-limiting step in the biosynthesis of glutathione (GSH). To evaluate the protective role of cellular GSH against arsenic-induced oxidative stress in Caenorhabditis elegans (C. elegans), we examined the effect of the C. elegans ortholog of GCS(h), gcs-1, in response to inorganic arsenic exposure. We have evaluated the responses of wild-type and gcs-1 mutant nematodes to both inorganic arsenite (As(III)) and arsenate (As(V)) ions and found that gcs-1 mutant nematodes are more sensitive to arsenic toxicity than that of wild-type animals. The amount of metal ion required to kill half of the population of worms falls in the order of wild-type / As(V) > gcs-1 / As(V) > wild-type / As(III) > gcs-1 / As(III). gcs-1 mutant nematodes also showed an earlier response to the exposure of As(III) and As(V) than that of wild-type animals. Addition of GSH significantly raised the survival rate of gcs-1mutant worms compared to As(III)-treated worms alone. These results indicate 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.

Nate Szewczyk et al. (2002) West Coast Worm Meeting "Constitutive promotion of muscle protein degradation by FGF is prevented by a DAF-2 signaling pathway"

Leah Parkinson, Brant Peterson, Nate Szewczyk, Lew Jacobson, Sami Barmada

[West Coast Worm Meeting, 2002]

In mammals, insulin and insulin-like growth factor (IGF) promote protein accumulation in muscle as the result of increased protein synthesis and decreased protein degradation. Under conditions of low insulin signaling (as in untreated diabetes) muscle wasting is observed as the result of decreased protein synthesis and increased protein degradation. Despite obvious clinical importance, intramuscular mechanisms by which insulin opposes protein degradation are not well characterized.

Ephraim Tsalik et al. (2002) West Coast Worm Meeting "AIY-Mediated Temperature Modulation of Behavior"

Ephraim Tsalik, Oliver Hobert

[West Coast Worm Meeting, 2002]

Thermotaxis has served as one of the key behavioral paradigms in C. elegans since its initial characterization in 1975 (Hedgecock and Russell, PNAS, 1975. 72(10):4061-5). With the neuronal pathway mediating thermosensation established, there has been comparatively little advance in understanding how temperature input might relate to other known C. elegans behaviors (Mori and Ohshima, Nature. 1995. 376:344-348). We have begun a preliminary analysis of how various behaviors are modulated by temperature as well as what role the AIY interneuron class plays in this modulation. By testing various mutant backgrounds as well as laser ablation studies, we have looked at known behaviors such as defecation, chemotaxis and radial locomotion. We have also analyzed a new behavior, which we call thermokinesis and define as the temperature and experience modulated movement of an animal with no specified body-axis orientation. This behavior is based on the previously described thrashing of worms in liquid media (Miller et al., PNAS, 1996. 93(22):12593-8), (Tsalik and Hobert, 2001 International C. elegans Meeting).

Rock Pulak et al. (2002) East Coast Worm Meeting "Multi-parameter & Dual Color Fluorescence Analysis and Flow Sorting of C. elegans."

Britta Moellers, Rock Pulak, Jen Kean

[East Coast Worm Meeting, 2002]

We have previously reported single color applications for the COPAS BIOSORT, such as live-from-dead assays (using propidium iodide or Sytox Green) or male-from-hermaphrodite separation (using wheat germ agglutinin-phycoerytherin), as well as protocols to isolate transgenic animals with predefined levels of expression of a fluorescent protein from specific promoters of interest. We now demonstrate multi-parameter and dual color analysis and how this is accomplished on the BIOSORT.

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.