Caenorhabditis Elegans Research Articles

Monomeric far-red and near-infrared fluorescent biliproteins of ultrahigh brightness.

Far-red and near-infrared fluorescent proteins have regions of maximum transmission in most tissues and can be widely used as fluorescent biomarkers. We report that fluorescent phycobiliproteins originating from the phycobilisome core subunit ApcF2 can covalently bind biliverdin, named BDFPs. To further improve BDFPs, we conducted a series of studies. Firstly, we mutated K53Q and T144A of BDFPs to increase their effective brightness up to 190% in vivo. Secondly, by homochromatic tandem fusion of high-brightness BDFPs to achieve monomerization, which increases the effective brightness by up to 180% in vivo, and can effectively improve the labeling effect. By combining the above two approaches, the brightness of the tandem BDFPs was much improved compared with that of the previously reported fluorescent proteins in a similar spectral range. The tandem BDFPs were expressed stably while maintaining fluorescence in mammalian cells and Caenorhabditis elegans. They were also photostable and resistant to high temperature, low pH, and chemical denaturation. The tandem BDFPs advantages were proved in applications as biomarkers for imaging in super-resolution microscopy.

Distinct members of the Caenorhabditis elegans CeMbio reference microbiota exert cryptic virulence that is masked by host defense.

Microbiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. Understanding the ability of each distinct community member to promote or impair host health, alone or in the context of the community, is imperative for understanding how differences in community structure affect host health and vice versa. Recently, a reference 12-member microbiota for the model organism Caenorhabditis elegans, known as CeMbio, was defined. Here, we show the differential ability of each CeMbio bacterial species to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh-WNT, and HLH-30/TFEB pathways. Although distinct CeMbio members differed in their ability to activate the PMK-1/p38 pathway, the ability to do so did not correlate with bacterial-induced lifespan reduction in wild-type or immunodeficient animals. In contrast, most species activated HLH-30/TFEB and showed virulence toward hlh-30-deficient animals. These results suggest that the microbiota of C. elegans is rife with bacteria that can shorten the host's lifespan if host defense is compromised and that HLH-30/TFEB is a fundamental and key host protective factor.

Label-free Brillouin endo-microscopy for the quantitative 3D imaging of sub-micrometre biology.

This report presents an optical fibre-based endo-microscopic imaging tool that simultaneously measures the topographic profile and 3D viscoelastic properties of biological specimens through the phenomenon of time-resolved Brillouin scattering. This uses the intrinsic viscoelasticity of the specimen as a contrast mechanism without fluorescent tags or photoacoustic contrast mechanisms. We demonstrate 2 μm lateral resolution and 320 nm axial resolution for the 3D imaging of biological cells and Caenorhabditis elegans larvae. This has enabled the first ever 3D stiffness imaging and characterisation of the C. elegans larva cuticle in-situ. A label-free, subcellular resolution, and endoscopic compatible technique that reveals structural biologically-relevant material properties of tissue could pave the way toward in-vivo elasticity-based diagnostics down to the single cell level.

Unveiling of Indanone‐Benzimidazole Hybrids as Anti‐Alzheimer's Agents: Computational and Experimental Studies

AbstractThe growing concern of Alzheimer's disease underscores the urgent requirement for the development of novel therapeutic agents. In this study, a series of 15 hybrid molecules containing Indanone‐Benzimidazole heterocycles were designed utilizing the molecular hybridization approach. The synthesized molecules were characterized by spectroscopic techniques and their anti‐Alzheimer's behaviour were examined. Biological assessment demonstrated that compounds 14 and 15 exhibited significant reduction of “human” amyloid beta (Aβ) peptide aggregation, expressing on transgenic Caenorhabditis elegans (C. elegans) strain CL4176. These compounds were further evaluated for their AChE inhibitory effects in transgenic C. elegans strain CL2006 and found significant. Molecular docking investigations have elucidated the commendable affinity exhibited by the studied ligands towards the Aβ pentamer (PDB: 2BEG) and acetylcholinesterase (AChE) (PDB: 4EY7). Subsequent to these docking studies, molecular dynamics simulations were conducted, affirming the stability of both ligands in association with the Aβ pentamer and ACh. Additionally, Density functional theory (DFT) calculations were performed by using B3LYP energy level with the basis set 6–311 G (d, p) basis set to correlate with experimental results. Taken together, all these findings evidenced the experimental results and this study sheds light on the anti‐Alzheimer's potential of Indanone‐Benzimidazole hybrids.

BmATAD3A mediates mitochondrial ribosomal protein expression to maintain the mitochondrial energy metabolism of the silkworm, Bombyx mori.

ATAD3A is a mitochondrial membrane protein belonging to the ATPase family that contains the AAA+ domain. It is widely involved in mitochondrial metabolism, protein transport, cell growth, development and other important life processes. It has previously been reported that the deletion of ATAD3A causes growth and development defects in humans, mice and Caenorhabditis elegans. To delve into the mechanism underlying ATAD3A defects and their impact on development, we constructed a Bombyx mori ATAD3A (BmATAD3A) defect model in silkworm larvae. We aim to offer a reference for understanding ATAD3A genetic defects and elucidating the molecular regulatory mechanisms. The results showed that knockout of the BmATAD3A gene significantly affected the weight, survival rate, ATPase production and mitochondrial metabolism of individuals after 24h of incubation. Combined metabolomics and transcriptomics analysis further demonstrated that BmATAD3A knockout inhibits amino acid biosynthesis through the regulation of mitochondrial ribosomal protein expression. Simultaneously, our findings indicate that BmATAD3A knockout impeded mitochondrial activity and ATPase synthesis and suppressed the mitochondrial oxidative phosphorylation pathway through B.mori mitochondrial ribosomal protein L11 (BmmRpL11). These results provide novel insights into the molecular mechanisms involved in the inhibition of development caused by ATAD3A deficiency, offering a potential direction for targeted therapy in diseases associated with abnormal ATAD3A expression.

Interaction between a J-domain co-chaperone and a specific Argonaute protein contributes to microRNA function in animals.

MicroRNAs (miRNAs) are essential regulators of several biological processes. They are loaded onto Argonaute (AGO) proteins to achieve their repressive function, forming the microRNA-Induced Silencing Complex known asmiRISC. While several AGO proteins are expressed in plants and animals, it is still unclear why specific AGOs are strictly binding miRNAs. Here, we identified the co-chaperone DNJ-12 as a new interactor of ALG-1, one of the two major miRNA-specific AGOs in Caenorhabditis elegans. DNJ-12 does not interact with ALG-2, the other major miRNA-specific AGO, and PRG-1 and RDE-1, two AGOs involved in other small RNA pathways, making it a specific actor in ALG-1-dependent miRNA-mediated gene silencing. The loss of DNJ-12 causes developmental defects associated with defective miRNA function. Using the Auxin Inducible Degronsystem, a powerful tool to acutely degrade proteins in specific tissues, we show that DNJ-12 depletion hampers ALG-1 interaction with HSP70, a chaperone required for miRISC loading in vitro. Moreover, DNJ-12 depletion leads to the decrease of several miRNAs and prevents their loading onto ALG-1. This study uncovers the importance of a co-chaperone for the miRNA function in vivo and provides insights to explain how different small RNAs associate with specific AGO in animals.

Anti-Aging and Neurorescue Effects of Loquat in Caenorhabditis elegans and Electrochemical Quantification of Dopamine Neurotransmitter

Anti-Aging and Neurorescue Effects of Loquat in <i>Caenorhabditis elegans</i> and Electrochemical Quantification of Dopamine Neurotransmitter

A tonically active master neuron modulates mutually exclusive motor states at two timescales.

Continuity of behaviors requires animals to make smooth transitions between mutually exclusive behavioral states. Neural principles that govern these transitions are not well understood. Caenorhabditis elegans spontaneously switch between two opposite motor states, forward and backward movement, a phenomenon thought to reflect the reciprocal inhibition between interneurons AVB and AVA. Here, we report that spontaneous locomotion and their corresponding motor circuits are not separately controlled. AVA and AVB are neither functionally equivalent nor strictly reciprocally inhibitory. AVA, but not AVB, maintains a depolarized membrane potential. While AVA phasically inhibits the forward promoting interneuron AVB at a fast timescale, it maintains a tonic, extrasynaptic excitation on AVB over the longer timescale. We propose that AVA, with tonic and phasic activity of opposite polarities on different timescales, acts as a master neuron to break the symmetry between the underlying forward and backward motor circuits. This master neuron model offers a parsimonious solution for sustained locomotion consisted of mutually exclusive motor states.

Deciphering antifungal and antibiofilm mechanisms of isobavachalcone against Cryptococcus neoformans through RNA-seq and functional analyses

Cryptococcus neoformans has been designated as critical fungal pathogens by the World Health Organization, mainly due to limited treatment options and the prevalence of antifungal resistance. Consequently, the utilization of novel antifungal agents is crucial for the effective treatment of C. neoformans infections. This study exposed that the minimum inhibitory concentration (MIC) of isobavachalcone (IBC) against C. neoformans H99 was 8 µg/mL, and IBC dispersed 48-h mature biofilms by affecting cell viability at 16 µg/mL. The antifungal efficacy of IBC was further validated through microscopic observations using specific dyes and in vitro assays, which confirmed the disruption of cell wall/membrane integrity. RNA-Seq analysis was employed to decipher the effect of IBC on the C. neoformans H99 transcriptomic profiles. Real-time quantitative reverse transcription PCR (RT-qPCR) analysis was performed to validate the transcriptomic data and identify the differentially expressed genes. The results showed that IBC exhibited various mechanisms to impede the growth, biofilm formation, and virulence of C. neoformans H99 by modulating multiple dysregulated pathways related to cell wall/membrane, drug resistance, apoptosis, and mitochondrial homeostasis. The transcriptomic findings were corroborated by the antioxidant analyses, antifungal drug sensitivity, molecular docking, capsule, and melanin assays. In vivo antifungal activity analysis demonstrated that IBC extended the lifespan of C. neoformans-infected Caenorhabditis elegans. Overall, the current study unveiled that IBC targeted multiple pathways simultaneously to inhibit growth significantly, biofilm formation, and virulence, as well as to disperse mature biofilms of C. neoformans H99 and induce cell death.

Impacts of superfine grinding on structural characteristics and lipid‐lowering effect of bitter melon polysaccharides

SummaryIn this study, the effects of superfine grinding on the structural and physicochemical properties of bitter melon polysaccharides (BPS) were investigated, and Caenorhabditis elegans model was used to evaluate fat‐lowering bioactivities of BPS. Results illustrated that superfine grinding resulted in high extraction of BPSs yielding with altered microstructure, different monosaccharide compositions and molecular weights. In addition, improved water/oil‐holding capacity, solubility and swelling capacity of polysaccharides were observed following superfine grinding. Furthermore, C. elegans study revealed that BPSs exhibited strong inhibitory effects on lipid accumulation, especially BPS‐25 (extracted from bitter melon treated with superfine grinding) reducing the triglyceride content from 9.49 to 1.85 mg g−1.prot. Mechanistic study showed that the lipid‐lowering effects of BPSs largely dependent on the insulin signalling pathway, fatty acid oxidation or lipolysis pathways. In all, our study underscore that superfine grinding can effectively improve the lipid‐lowing effects of bitter melon polysaccharides.

Nematicidal Activity of 20-Deoxyingenol-3-angelate from Euphorbia peplus Latex Through Protein Kinase C Isotype TPA-1.

The latex of Euphorbia peplus and its major component 20-deoxyingenol-3-angelate (DI3A) displayed significant nematicidal activity against Caenorhabditis elegans and Panagrellus redivivus. DI3A treatment inhibited the growth and development of nematodes and caused significantly negative effects on locomotion behavior, reproduction, and accumulation of reactive oxygen species. Transcriptome analysis indicated that differential expression genes in DI3A-treated C. elegans were mainly associated with the metabolism, growth, and development process, which were further confirmed by RT-qPCR experiments. The expression level of TPA-1 gene encoding a protein kinase C isotype was obviously upregulated by DI3A treatment, and knockdown of TPA-1 by RNAi technology in the nematode could relieve the growth-inhibitory effect of DI3A. Metabolic analysis indicated that DI3A was hardly metabolized by C. elegans, but a glycosylated indole derivative was specifically accumulated likely due to the activation of detoxification. Overall, our findings suggested that DI3A from E. peplus latex exerted a potent nematicidal effect through the gene TPA-1, which provides a potential target for the control of nematodes and also suggests the potential application value of E. peplus latex and DI3A as botanical nematicides.

Phyllodulcin from the hexane fraction of Hydrangea macrophylla inhibits glucose-induced lipid accumulation and reactive oxygen species (ROS) generation in Caenorhabditis elegans.

We confirmed that the hexane layer of Hydrangea macrophylla leaf extract (HLH) is rich in phyllodulcin (PD), an alternative sweetener through HPLC analysis. To investigate in vivo activity of HLH and its PD, acute toxicity and growth rate of Caenorhabditis elegans were tested and there are no clinical abnormalities at 125-500μg/mL of HLH. HLH decreased the total lipid and TG contents dose-dependently glucose (GLU) induced obese worms. Also, HLH increased survival rates under oxidative and thermal stress and decreased body ROS contents significantly. Such antioxidant properties of HLH were attributed to the enhanced activity of the antioxidant enzyme catalase. To determine whether the effect of HLH was by PD, worms were treated with PD (concentration contained in HLH), and inhibitory effects on total lipids and ROS were observed. Our results suggest that HLH and its PD as a natural alternative sweetener can be material to improve metabolic diseases.

Non-Mammalian Models for Understanding Neurological Defects in RASopathies

RASopathies, a group of neurodevelopmental congenital disorders stemming from mutations in the RAS/MAPK pathway, present a unique opportunity to delve into the intricacies of complex neurological disorders. Afflicting approximately one in a thousand newborns, RASopathies manifest as abnormalities across multiple organ systems, with a pronounced impact on the central and peripheral nervous system. In the pursuit of understanding RASopathies’ neurobiology and establishing phenotype–genotype relationships, in vivo non-mammalian models have emerged as indispensable tools. Species such as Danio rerio, Drosophila melanogaster, Caenorhabditis elegans, Xenopus species and Gallus gallus embryos have proven to be invaluable in shedding light on the intricate pathways implicated in RASopathies. Despite some inherent weaknesses, these genetic models offer distinct advantages over traditional rodent models, providing a holistic perspective on complex genetics, multi-organ involvement, and the interplay among various pathway components, offering insights into the pathophysiological aspects of mutations-driven symptoms. This review underscores the value of investigating the genetic basis of RASopathies for unraveling the underlying mechanisms contributing to broader neurological complexities. It also emphasizes the pivotal role of non-mammalian models in serving as a crucial preliminary step for the development of innovative therapeutic strategies.

Fibration symmetries and cluster synchronization in the Caenorhabditis elegans connectome.

Capturing how the Caenorhabditis elegans connectome structure gives rise to its neuron functionality remains unclear. It is through fiber symmetries found in its neuronal connectivity that synchronization of a group of neurons can be determined. To understand these we investigate graph symmetries and search for such in the symmetrized versions of the forward and backward locomotive sub-networks of the Caenorhabditi elegans worm neuron network. The use of ordinarily differential equations simulations admissible to these graphs are used to validate the predictions of these fiber symmetries and are compared to the more restrictive orbit symmetries. Additionally fibration symmetries are used to decompose these graphs into their fundamental building blocks which reveal units formed by nested loops or multilayered fibers. It is found that fiber symmetries of the connectome can accurately predict neuronal synchronization even under not idealized connectivity as long as the dynamics are within stable regimes of simulations.

Sperm development and structure in Bursaphelenchus luxuriosae (Nematoda: Aphelenchoidea: Aphelenchoididae)

Summary Sperm development and structure in the wood-inhabiting fungal and plant-feeding nematode, Bursaphelenchus luxuriosae, were studied using transmission electron microscopy to evaluate interspecific similarities and differences of spermatozoa in nematodes. In general, spermatogenesis in B. luxuriosae fits the ‘rhabditid’ pattern supported by morphological and phylogenetic analysis of the order Rhabditida. Spermatocyte development includes formation of complexes of fibrous bodies (FBs) with membranous organelles (MOs), the complexes dissociate in the spermatids into separate components, and the immature sperm contain MOs but lack FBs, which transform into a dense matrix of sperm cytoplasm. The female spermatheca contains mature spermatozoa as bipolar cells subdivided into a pseudopod devoid of organelles and a main cell body containing a nucleus without a nuclear envelope, numerous mitochondria, and peripheral MOs as pouches opening to the exterior via pores. Data on B. luxuriosae are used for analysis of variable quantitative and morphological characteristics of spermatozoa in Aphelenchoidea. General size of spermatozoa and their MOs have little value for comparative analysis. The MO knobbles look uniform in immature spermatozoa of each aphelenchoidid species studied and may be considered as a taxonomically specific ultrastructural feature. The presence or absence of FBs in immature spermatozoa demonstrates the diagnostic value of the aphelenchoidid sperm structure at the species level. Analysis also shows close similarity of spermatozoa in Bursaphelenchus spp. and Caenorhabditis elegans, the model species with comprehensive data on sperm biology. This may be used to identify new ways for the control and suppression of harmful nematode species such as B. xylophilus.

Chitosan-based delivery of fish codon-optimised Caenorhabditis elegans FAT-1 and FAT-2 boosts EPA and DHA biosynthesis in Sparus aurata

AbstractOmega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) are essential fatty acids required in healthy balanced diets for humans. To induce sustained production of n-3 LC-PUFA in gilthead seabream (Sparus aurata), chitosan-tripolyphosphate (TPP) nanoparticles encapsulating plasmids expressing fish codon-optimised Caenorhabditis elegans FAT-1 and FAT-2 were intraperitoneally administered every 4 weeks (3 doses in total, each of 10 μg plasmid per g of body weight). Growth performance and metabolic effects of chitosan-TPP complexed with pSG5 (empty plasmid), pSG5-FAT-1, pSG5-FAT-2 and pSG5-FAT-1 + pSG5-FAT-2 were assessed 70 days post-treatment. Tissue distribution analysis showed high expression levels of fish codon-optimised FAT-1 and FAT-2 in the liver (&gt; 200-fold). Expression of fat-1 and fat-1 + fat-2 increased weight gain. Fatty acid methyl esters assay revealed that co-expression of fat-1 and fat-2 increased liver production and muscle accumulation of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and total n-3 LC-PUFA, while decreased the n-6/n-3 ratio. Co-expression of fat-1 and fat-2 downregulated srebf1 and genes encoding rate-limiting enzymes for de novo lipogenesis in the liver, leading to decreased circulating triglycerides and cholesterol. In contrast, FAT-2 and FAT-1 + FAT-2 upregulated hepatic hnf4a, nr1h3 and key enzymes in glycolysis and the pentose phosphate pathway. Our findings demonstrate for the first time efficient and sustained production of EPA and DHA in animals after long-term treatment with chitosan-TPP-DNA nanoparticles expressing FAT-1 and FAT-2, which enabled the production of functional fish rich in n-3 LC-PUFA for human consumption.

Anti-aging effect of peptides on Caenorhabditis elegans: a meta-analysis.

Peptides have been studied in Caenorhabditis elegans for anti-aging research recently. Due to the lack of sufficient evidence, we conducted this meta-analysis focusing on the anti-aging effect of peptides in C. elegans to provide more convincing evidence. A literature search in PubMed, SCOUPUS, and Web of Science databases yielded 2879 articles. After removing duplicates and based on inclusion criteria and STAIR checklist quality assessment, 9 articles were selected. Data extraction and analysis showed that, compared to the control group without peptide intervention, peptide supplementation significantly reduced nematode mortality risk (HR= 0.54, 95% CI = 0.47, 0.62; p < 0.05), significantly increased the pharyngeal pumping rate (SMD = 1.64, 95% CI = 0.87, 2.41; p < 0.05), bending frequency (SMD = 1.67, 95% CI =1.16, 2.18; p < 0.05), and significantly decreased the accumulation of lipofuscin levels within nematodes (SMD = -4.48, 95% CI = -6.85, -2.12; p < 0.05). Additionally, subgroup analysis showed that doses ranging from 0.1-1 kg m3 ^-1 (HR= 0.50, 95% CI = 0.38, 0.65; p < 0.05) displayed better anti-aging effects compared to other dose ranges. The findings suggest that peptides can significantly extend the lifespan of C. elegans under normal circumstances and improve three indicators of healthylife. More importantly, subgroup analysis revealed that a dosage of 0.1-1 kg m3 ^-1 demonstrated superior anti-aging effects. This meta-analysis provides more convincing evidence that peptides can play an anti-aging role in C. elegans. This article is protected by copyright. All rights reserved.

Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans.

Reduced insulin/IGF-1 signalling (rIIS) improves survival across diverse taxa and there is a growing interest in its role in regulating immune function. Whilst rIIS can improve anti-bacterial resistance, the consequences for anti-viral immunity are yet to be systematically examined. Here, we show that rIIS in adult Caenorhabditis elegans increases the expression of key genes in two different anti-viral immunity pathways, whilst reducing viral load in old age, increasing survival and reducing rate-of-senescence under infection by naturally occurring positive-sense single-stranded RNA Orsay virus. We found that both drh-1 in the anti-viral RNA interference (RNAi) pathway and cde-1 in the terminal uridylation-based degradation of viral RNA pathway were upregulated in early adulthood under rIIS and increased anti-viral resistance was not associated with reproductive costs. Remarkably, rIIS increased anti-viral gene expression only in infected worms, potentially to curb the costs of constitutively upregulated immunity. RNA viruses are found across taxa from plants to mammals and we demonstrate a novel role for rIIS in regulating resistance to viral infection. We therefore highlight this evolutionarily conserved signalling pathway as a promising therapeutic target to improve anti-viral immunity.

Caenorhabditis elegans telomere-binding proteins TEBP-1 and TEBP-2 adapt the Myb module to dimerize and bind telomeric DNA

Protecting chromosome ends from misrecognition as double-stranded (ds) DNA breaks is fundamental to eukaryotic viability. The protein complex shelterin prevents a DNA damage response at mammalian telomeres. Mammalian shelterin proteins TRF1 and TRF2 and their homologs in yeast and protozoa protect telomeric dsDNA. N-terminal homodimerization and C-terminal Myb-domain-mediated dsDNA binding are two structural hallmarks of end protection by TRF homologs. Yet our understanding of how Caenorhabditis elegans protects its telomeric dsDNA is limited. Recently identified C. elegans proteins TEBP-1 (also called DTN-1) and TEBP-2 (also called DTN-2) are functional homologs of TRF proteins, but how they bind DNA and whether or how they dimerize is not known. TEBP-1 and TEBP-2 harbor three Myb-containing domains (MCDs) and no obvious dimerization domain. We demonstrate biochemically that only the third MCD binds DNA. We solve the X-ray crystal structure of TEBP-2 MCD3 with telomeric dsDNA to reveal the structural mechanism of telomeric dsDNA protection in C. elegans. Mutagenesis of the DNA-binding site of TEBP-1 and TEBP-2 compromises DNA binding in vitro, and increases DNA damage signaling, lengthens telomeres, and decreases brood size in vivo. Via an X-ray crystal structure, biochemical validation of the dimerization interface, and SEC-MALS analysis, we demonstrate that MCD1 and MCD2 form a composite dimerization module that facilitates not only TEBP-1 and TEBP-2 homodimerization but also heterodimerization. These findings provide fundamental insights into C. elegans telomeric dsDNA protection and highlight how different eukaryotes have evolved distinct strategies to solve the chromosome end protection problem.

Tryptophanyl-tRNA synthetase-1 (WARS-1) depletion and high tryptophan concentration lead to genomic instability in Caenorhabditis elegans

The fidelity of translation is ensured by a family of proteins named aminoacyl-tRNA synthetases (ARSs), making them crucial for development and survival. More recently, mutations in the tryptophanyl-tRNA synthetase 1 (WARS1) have been linked to various human diseases, from intellectual disability to various types of cancer. To understand the function of WARS1, we investigated the effect of WARS-1 depletion during the mitotic and meiotic cell cycle in the developing germline of Caenorhabditis elegans (C. elegans) and demonstrated the role of WARS-1 in genome integrity. wars-1 knockdown results in cell cycle arrest of the mitotically active germ cells. Such mitotic arrest is also associated with canonical DNA damage-induced checkpoint signaling in mitotic and meiotic germ cells. Significantly, such DNA checkpoint activation is associated with the morphological anomalies in chromatin structures that are the hallmarks of genome instability, such as the formation of chromatin bridges, micronuclei, and chromatin buds. We demonstrated that knocking down wars-1 results in an elevation of the intracellular concentration of tryptophan and its catabolites, a surprising finding emphasizing the impact of cellular amino acid availability and organismal/individual dietary uptake on genome integrity. Our result demonstrates that exposing C. elegans to a high tryptophan dosage leads to DNA damage checkpoint activation and a significant increase in the tryptophan metabolites. Targeting tryptophan catabolism, the least utilized amino acid in nature, can be important in developing new cancer therapeutic approaches. All in all, we have strong evidence that knocking down wars-1 results in defects in genomic integrity.