Review of Biological Effects of Acute and Chronic Radiation Exposure on Caenorhabditis elegans

Knowledge regarding complex radiation responses in biological systems can be enhanced using genetically amenable model organisms. In this manuscript, we reviewed the use of the nematode, Caenorhabditis elegans (C. elegans), as a model organism to investigate radiation’s biological effects. Diverse types of experiments were conducted on C. elegans, using acute and chronic exposure to different ionizing radiation types, and to assess various biological responses. These responses differed based on the type and dose of radiation and the chemical substances in which the worms were grown or maintained. A few studies compared responses to various radiation types and doses as well as other environmental exposures. Therefore, this paper focused on the effect of irradiation on C. elegans, based on the intensity of the radiation dose and the length of exposure and ways to decrease the effects of ionizing radiation. Moreover, we discussed several studies showing that dietary components such as vitamin A, polyunsaturated fatty acids, and polyphenol-rich food source may promote the resistance of C. elegans to ionizing radiation and increase their life span after irradiation.

Download Full-text

Materials and toxicological approaches to study metal and metal-oxide nanoparticles in the model organism Caenorhabditis elegans

Materials Horizons ◽

10.1039/c7mh00166e ◽

2017 ◽

Vol 4 (5) ◽

pp. 719-746 ◽

Cited By ~ 11

Author(s):

Laura Gonzalez-Moragas ◽

Laura L. Maurer ◽

Victoria M. Harms ◽

Joel N. Meyer ◽

Anna Laromaine ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Metal Oxide ◽

Metal Oxide Nanoparticles ◽

Model Organism ◽

Oxide Nanoparticles ◽

C Elegans ◽

Biological Responses ◽

Approaches To Study

The C. elegans biological responses to metal-based nanoparticles are reviewed. A cross-disciplinary workflow for nanoparticles screening in vivo is proposed.

Download Full-text

The glycomes of Caenorhabditis elegans and other model organisms

Biochemical Society Symposium ◽

10.1042/bss0690117 ◽

2002 ◽

Vol 69 ◽

pp. 117-134 ◽

Cited By ~ 47

Author(s):

Stuart M. Haslam ◽

David Gems ◽

Howard R. Morris ◽

Anne Dell

Keyword(s):

Caenorhabditis Elegans ◽

Current Knowledge ◽

Structural Data ◽

Model Organisms ◽

Entire Genome ◽

C Elegans ◽

The Face ◽

Area Of Concern ◽

Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

Download Full-text

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

Anesthesiology ◽

10.1097/00000542-199610000-00027 ◽

1996 ◽

Vol 85 (4) ◽

pp. 901-912 ◽

Cited By ~ 38

Author(s):

Michael C. Crowder ◽

Laynie D. Shebester ◽

Tim Schedl

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Time Course ◽

Model Organism ◽

Volatile Anesthetic ◽

Volatile Anesthetics ◽

Effective Concentration ◽

Forward Genetics ◽

C Elegans ◽

Median Effective Concentration

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.

Download Full-text

Stochastic left–right neuronal asymmetry in Caenorhabditis elegans

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2015.0407 ◽

2016 ◽

Vol 371 (1710) ◽

pp. 20150407 ◽

Cited By ~ 16

Author(s):

Amel Alqadah ◽

Yi-Wen Hsieh ◽

Rui Xiong ◽

Chiou-Fen Chuang

Keyword(s):

Caenorhabditis Elegans ◽

Molecular Mechanisms ◽

Neurological Diseases ◽

Calcium Signalling ◽

Model Organism ◽

Brain Asymmetry ◽

C Elegans ◽

Left And Right ◽

Left Right Asymmetry ◽

Neuronal Asymmetry

Left–right asymmetry in the nervous system is observed across species. Defects in left–right cerebral asymmetry are linked to several neurological diseases, but the molecular mechanisms underlying brain asymmetry in vertebrates are still not very well understood. The Caenorhabditis elegans left and right amphid wing ‘C’ (AWC) olfactory neurons communicate through intercellular calcium signalling in a transient embryonic gap junction neural network to specify two asymmetric subtypes, AWC OFF (default) and AWC ON (induced), in a stochastic manner. Here, we highlight the molecular mechanisms that establish and maintain stochastic AWC asymmetry. As the components of the AWC asymmetry pathway are highly conserved, insights from the model organism C. elegans may provide a window onto how brain asymmetry develops in humans. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.

Download Full-text

An Evolutionarily Conserved Pathway Essential for Orsay Virus Infection of Caenorhabditis elegans

mBio ◽

10.1128/mbio.00940-17 ◽

2017 ◽

Vol 8 (5) ◽

Cited By ~ 13

Author(s):

Hongbing Jiang ◽

Kevin Chen ◽

Luis E. Sandoval ◽

Christian Leung ◽

David Wang

Keyword(s):

Caenorhabditis Elegans ◽

Virus Infection ◽

Tyrosine Kinase ◽

Model Organism ◽

Wiskott Aldrich Syndrome ◽

C Elegans ◽

Evolutionarily Conserved ◽

Conserved Genes ◽

Orsay Virus ◽

Syndrome Protein

ABSTRACT Many fundamental biological discoveries have been made in Caenorhabditis elegans. The discovery of Orsay virus has enabled studies of host-virus interactions in this model organism. To identify host factors critical for Orsay virus infection, we designed a forward genetic screen that utilizes a virally induced green fluorescent protein (GFP) reporter. Following chemical mutagenesis, two Viro (virus induced reporter off) mutants that failed to express GFP were mapped to sid-3, a nonreceptor tyrosine kinase, and B0280.13 (renamed viro-2), an ortholog of human Wiskott-Aldrich syndrome protein (WASP). Both mutants yielded Orsay virus RNA levels comparable to that of the residual input virus, suggesting that they are not permissive for Orsay virus replication. In addition, we demonstrated that both genes affect an early prereplication stage of Orsay virus infection. Furthermore, it is known that the human ortholog of SID-3, activated CDC42-associated kinase (ACK1/TNK2), is capable of phosphorylating human WASP, suggesting that VIRO-2 may be a substrate for SID-3 in C. elegans. A targeted RNA interference (RNAi) knockdown screen further identified the C. elegans gene nck-1, which has a human ortholog that interacts with TNK2 and WASP, as required for Orsay virus infection. Thus, genetic screening in C. elegans identified critical roles in virus infection for evolutionarily conserved genes in a known human pathway. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection.

Download Full-text

Neuroligin dependence of social behaviour in Caenorhabditis elegans provides a model to investigate an autism-associated gene

Human Molecular Genetics ◽

10.1093/hmg/ddaa232 ◽

2020 ◽

Author(s):

Helena Rawsthorne ◽

Fernando Calahorro ◽

Emily Feist ◽

Lindy Holden-Dye ◽

Vincent O’Connor ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Genetic Variants ◽

Social Behaviour ◽

Animal Studies ◽

Model Organism ◽

Autism Spectrum ◽

C Elegans ◽

Important Regulator ◽

Human Mutation ◽

The Impact

Abstract Autism spectrum disorder (ASD) is characterized by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neuroligin in social circuitry and the impact of genetic variation to this gene is not fully understood. Indeed, in animal studies designed to model autism, there remains controversy regarding the role of neuroligin dysfunction in the expression of disrupted social behaviours. The model organism, Caenorhabditis elegans, offers an informative experimental platform to investigate the impact of genetic variants on social behaviour. In a number of paradigms, it has been shown that inter-organismal communication by chemical cues regulates C. elegans social behaviour. We utilize this social behaviour to investigate the effect of autism-associated genetic variants within the social domain of the research domain criteria. We have identified neuroligin as an important regulator of social behaviour and segregate the importance of this gene to the recognition and/or processing of social cues. We also use CRISPR/Cas9 to edit an R-C mutation that mimics a highly penetrant human mutation associated with autism. C. elegans carrying this mutation phenocopy the behavioural dysfunction of a C. elegans neuroligin null mutant, thus confirming its significance in the regulation of animal social biology. This highlights that quantitative behaviour and precision genetic intervention can be used to manipulate discrete social circuits of the worm to provide further insight into complex social behaviour.

Download Full-text

CAENORHABDITIS ELEGANS AS A MODEL OF AIR POLLUTION TOXICITY DURING DEVELOPMENT AND LIFESPAN

Innovation in Aging ◽

10.1093/geroni/igz038.366 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S97-S97

Author(s):

Amin Haghani ◽

Hans M Dalton ◽

Nikoo Safi ◽

Farimah Shirmohammadi ◽

Constantinos Sioutas ◽

...

Keyword(s):

Air Pollution ◽

Caenorhabditis Elegans ◽

Mouse Models ◽

High Throughput ◽

Molecular Mechanisms ◽

Cultured Cells ◽

Exposure Model ◽

C Elegans ◽

Biological Responses ◽

Short Term Exposure

Abstract Air pollution (AirPoll) is among the leading human mortality risk factors and yet little is known about the molecular mechanisms of this global environmental toxin. Our recent studies using mouse models even showed genetic variation and sex can alter biological responses to air pollution. To expand genetic studies of AirPoll toxicity throughout the lifespan, we introduced Caenorhabditis elegans as a new AirPoll exposure model which has a short lifespan, high throughput capabilities and shared longevity pathways with mammals. Acute exposure of C. elegans to airborne nanosized AirPoll matter (nPM) caused similar gene expression changes to our prior findings in cell culture and mouse models. Initial C. elegans responses to nPM included antioxidant, inflammatory and Alzheimer homolog genes. The magnitude of changes was dependent on the developmental stage of the worms. Even short term exposure of C. elegans to nPM altered developmental and lifespan hormetic effects, with pathways that included skn-1/Nrf family antioxidant responses. We propose C. elegans as a new and complementary model for mouse and cultured cells to study AirPoll across the lifespan. Future chronic nPM exposure and high throughput genetic screening of C. elegans can identify other major regulators of the developmental and lifespan effects of air pollution. This work was supported by grants R01AG051521 (CEF); R21AG05020 (CEF); Cure Alzheimer’s Fund (CEF); R01GM109028 (SPC), F31AG051382 (HMD) and T32AG000037 (HMD), T32AG052374 (AH).

Download Full-text

High-throughput transcriptome sequencing reveals extremely high doses of ionizing radiation-response genes in Caenorhabditis elegans

Toxicology Research ◽

10.1039/c9tx00101h ◽

2019 ◽

Vol 8 (5) ◽

pp. 754-766 ◽

Cited By ~ 1

Author(s):

Youqin Xu ◽

Lina Chen ◽

Mengyi Liu ◽

Yanfang Lu ◽

Yanwei Yue ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Ionizing Radiation ◽

Differential Expression ◽

Gene Families ◽

Rna Degradation ◽

Cellular Growth ◽

Radiation Response ◽

Signalling Pathways ◽

C Elegans ◽

High Doses

Abstract This study sought novel ionizing radiation-response (IR-response) genes in Caenorhabditis elegans (C. elegans). C. elegans was divided into three groups and exposed to different high doses of IR: 0 gray (Gy), 200 Gy, and 400 Gy. Total RNA was extracted from each group and sequenced. When the transcriptomes were compared among these groups, many genes were shown to be differentially expressed, and these genes were significantly enriched in IR-related biological processes and pathways, including gene ontology (GO) terms related to cellular behaviours, cellular growth and purine metabolism and kyoto encyclopedia of genes and genomes (KEGG) pathways related to ATP binding, GTPase regulator activity, and RNA degradation. Quantitative reverse-transcription PCR (qRT-PCR) confirmed that these genes displayed differential expression across the treatments. Further gene network analysis showed a cluster of novel gene families, such as the guanylate cyclase (GCY), Sm-like protein (LSM), diacylglycerol kinase (DGK), skp1-related protein (SKR), and glutathione S-transferase (GST) gene families which were upregulated. Thus, these genes likely play important roles in IR response. Meanwhile, some important genes that are well known to be involved in key signalling pathways, such as phosphoinositide-specific phospholipase C-3 (PLC-3), phosphatidylinositol 3-kinase age-1 (AGE-1), Raf homolog serine/threonine-protein kinase (LIN-45) and protein cbp-1 (CBP-1), also showed differential expression during IR response, suggesting that IR response might perturb these key signalling pathways. Our study revealed a series of novel IR-response genes in Caenorhabditis elegans that might act as regulators of IR response and represent promising markers of IR exposure.

Download Full-text

Caenorhabditis elegans as a Model Organism to Evaluate the Antioxidant Effects of Phytochemicals

Molecules ◽

10.3390/molecules25143194 ◽

2020 ◽

Vol 25 (14) ◽

pp. 3194

Author(s):

Begoña Ayuda-Durán ◽

Susana González-Manzano ◽

Ana M. González-Paramás ◽

Celestino Santos-Buelga

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Model Organism ◽

Lipid Peroxides ◽

Biological Research ◽

Loss Of Function ◽

Fluorescent Reporters ◽

C Elegans ◽

High Degree

The nematode Caenorhabditis elegans was introduced as a model organism in biological research by Sydney Brenner in the 1970s. Since then, it has been increasingly used for investigating processes such as ageing, oxidative stress, neurodegeneration, or inflammation, for which there is a high degree of homology between C. elegans and human pathways, so that the worm offers promising possibilities to study mechanisms of action and effects of phytochemicals of foods and plants. In this paper, the genes and pathways regulating oxidative stress in C. elegans are discussed, as well as the methodological approaches used for their evaluation in the worm. In particular, the following aspects are reviewed: the use of stress assays, determination of chemical and biochemical markers (e.g., ROS, carbonylated proteins, lipid peroxides or altered DNA), influence on gene expression and the employment of mutant worm strains, either carrying loss-of-function mutations or fluorescent reporters, such as the GFP.

Download Full-text

Caenorhabditis elegans as an Emerging Model for Virus-Host Interactions

Journal of Virology ◽

10.1128/jvi.00509-17 ◽

2017 ◽

Vol 91 (23) ◽

Cited By ~ 10

Author(s):

Don B. Gammon

Keyword(s):

Caenorhabditis Elegans ◽

Virus Infection ◽

Fungal Pathogens ◽

Model Organism ◽

Artificial Infection ◽

Viral Pathogen ◽

Content Type ◽

Host Interactions ◽

C Elegans ◽

Infection Models

ABSTRACT Since 1999, Caenorhabditis elegans has been extensively used to study microbe-host interactions due to its simple culture, genetic tractability, and susceptibility to numerous bacterial and fungal pathogens. In contrast, virus studies have been hampered by a lack of convenient virus infection models in nematodes. The recent discovery of a natural viral pathogen of C. elegans and development of diverse artificial infection models are providing new opportunities to explore virus-host interplay in this powerful model organism.

Download Full-text