Project description:Exposure to cadmium is associated with a variety of human diseases. At low concentrations, cadmium activates the transcription of stress-responsive genes, which can prevent or repair the adverse effects caused by this metal. Using C. elegans, 290 genes were identified that are differentially expressed (≥1.5-fold) following a 4 or 24 hour exposure to cadmium. Several of these genes are known to be involved in metal detoxification, including mtl-1, mtl-2, cdr-1 and ttm-1, confirming the efficacy of the study. The majority, however, were not previously associated with metal-responsiveness and are novel. Gene Ontology analysis mapped these genes to cellular/ion trafficking, metabolic enzymes and proteolysis categories. RNAi-mediated inhibition of 50 cadmium-responsive genes resulted in an increased sensitivity to cadmium toxicity, demonstrating that these genes are involved in the resistance to cadmium toxicity. Several functional protein interacting networks were identified by interactome analysis. Within one network, the signaling protein KEL-8 was identified. Kel-8 protects C. elegans from cadmium toxicity in a mek-1 (MAPKK)-dependent manner. Because many C. elegans genes and signal transduction pathways are evolutionarily conserved, these results may contribute to the understanding of the functional roles of various genes in cadmium toxicity in higher organisms. Keywords: gene expression time course
Project description:This SuperSeries is composed of the following subset Series: GSE21008: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: atrazine GSE21010: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: cadmium GSE21011: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: fluoranthene Refer to individual Series
Project description:Effective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression. The objective of this research is to determine genomic and proteomic responses in the model nematode C. elegans to exposures to representatives of several classes of toxic industrial chemicals/materials (TICs/TIMs). A total of 3 chemicals (acrylamide, cadmium chloride, and mercuric chloride) were used in these experiments. Affymetrix GeneChip for C. elegans was used to examine genome-wide responses in the 19,000+ genes of this model organism. Mid-vulval L4 worms were exposed to one of four concentrations of acrylamide, cadmium or mercury for 4h and 8h. Exposures were performed in triplicate.
Project description:Infection of Pseudomonas donghuensis HYS strain and its fur deletion mutant in Caenorhabditis elegans was conducted to assess changes in the expression profile of Caenorhabditis elegans, and potential core virulence factors were identified by measuring the gene expression levels of the HYS colonizing the nematode's intestine. Preliminary studies indicate that P. donghuensis HYS exhibits significant toxicity towards Caenorhabditis elegans, yet the underlying mechanisms of this pronounced toxicity remain unclear. Previous work identified several virulence factors contributing to the toxicity of HYS through detection and functional validation; however, the molecular mechanisms responsible for its strong toxicity have not been elucidated. Therefore, we aim to analyze the mechanisms underlying HYS's pronounced toxicity by examining the responses of infected Caenorhabditis elegans. The Ferric uptake regulator (Fur) is responsible for maintaining iron homeostasis in Gram-negative bacteria, and given that HYS possesses a greater iron uptake capacity than other common species in the same genus, such as Pseudomonas aeruginosa, we hypothesize that Fur may play a critical role in the strong toxicity exhibited by HYS. Consequently, we infected Caenorhabditis elegans with both HYS and its fur deletion mutant and analyzed the changes in the expression profile of Caenorhabditis elegans. We observed a significant reduction in toxicity following the deletion of fur, indicating that Fur regulates core virulence factors. To identify these core virulence factors, we conducted transcriptomic sequencing of the pathogenic bacteria under various conditions and performed a screening for virulence factors.
Project description:Cadmium is a naturally occurring heavy metal, and it is widely used in industry. Due to its persistent toxic effect, cadmium is classified as a category one human carcinogen. Its toxicity has been extensively studied in different organisms, including the nematode Caenorhabditis elegans. To investigate the transcriptomic responses following cadmium during early life exposure, C. elegans larval were exposed either from L1 to L3 stage or L1 to L4 stage to 20 µM cadmium chloride. RNAseq was applied to identified the changes of the transcriptome and the pathways which are specific to each stage. Overall, the result revealed that the highest responsive genes in both exposure scenario were linked to oxidative stress, lipid metabolism and ion binding. Additionally, some of these genes are well characterized and linked to specific functions, but some have no known function, however these uncharacterized genes are differentially expressed in both stages as a result of cadmium toxicity.Numerous transcripts were identified in one stage but not at the other. Furthermore, a general trend was observed where a larger number of genes were differentially expressed at L3 stage compared to L4, which suggest stage specific sensitivity in response to cadmium exposure.
Project description:Effective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression. The objective of this research is to determine genomic and proteomic responses in the model nematode C. elegans to exposures to representatives of several classes of toxic industrial chemicals/materials (TICs/TIMs). A total of 3 chemicals (acrylamide, cadmium chloride, and mercuric chloride) were used in these experiments. Affymetrix GeneChip for C. elegans was used to examine genome-wide responses in the 19,000+ genes of this model organism.