Project description:The extent to which behavior is shaped by experience varies between individuals. Genetic differences contribute to this variation but the neural mechanisms are not understood. In this study, we identify a natural genetic variant of the dendritic scaffolding protein ARCP-1 that modifies individual behavioral flexibility in C. elegans. Disrupting ARCP-1 alters how previous oxygen experience modulates escape behavior in response to carbon dioxide. ARCP-1 normally suppresses CO2 aversion by inhibiting signaling from the BAG CO2-sensing neurons. To further investigate how disrupting ARCP-1 alters BAG function, we specifically labeled these neurons with GFP, used FACS to isolate the fluorescent cells from acutely dissociated arcp-1 mutant and control animals, and profiled their gene expression using RNA-Seq. We find transcriptional changes for a broad range of gene classes and link altered neuropeptide expression to increased CO2 aversion in the arcp-1 mutant.
Project description:To gain molecular insights on how NPR-8 regulates C. elegans defense against pathogen infection, we used RNA sequencing to profile gene expression in npr-8(ok1439) animals relative to wild-type animals with or without P. aeruginosa infection. We found that NPR-8 suppresses the expression of genes related to cuticle structure activity including collagen genes, and lack of NPR-8-mediated suppression in npr-8(ok1439) animals contributes to their improved survival against P. aeruginosa infection.
Project description:Purpose: The goals of this study are to identify cellular pathways to recover a-syn aggregation-mediated toxicity induced in response to CDC or BAG treatment on PD-iPSC derived mDA neurons. Methods: mRNA profiles of 30-day-old PD-mDA neurons with CDC or BAG treatment for 1 day were generated by deep sequencing, in duplicate, using Illumina HiSeq. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. Conclusions: Our study represents the detailed analysis of mDA neuronal transcriptomes in response to CDC or BAG treatments, with biologic replicates, generated by RNA-seq technology. Our results show that CDC or BAG treatment could rescue the toxcity from a-syn aggregation via purine metabolism / ion transport pathways.
Project description:Purpose: To uncover immune genes and pathways that are modulated by the GPCR/NPR-15 Methods: RNA was extracted from synchronized L4 stage npr-15(tm12539) and WT animals grown at 20 C using Qiagen extraction kits and following standard methods Results: RNA seq analyses shows enriched and signficant upregulated immune, neuropeptide, synaptic signaling and metabolism genes and pathways that are dependent on NPR-15 Conclusions: Our study uncovered NPR-15 to be modulator of the innate immunity in C. elegans
Project description:The Aryl hydrocarbon Receptor (AhR) is a transcription factor well known in vertebrate to play an essential role as xenobiotic sensor. On the contrary, no ligand has been identified to date for invertebrate AhR. In some model organisms such as D. melanogaster and C. elegans, AhR orthologs have physiological functions and their inability to bind prototypical ligands of vertebrate AhR such as tetrachlorodibenzo-p-dioxin (TCDD) suggests that the detoxification role of the receptor could be an adaptation acquired during evolution. To better understand the physiological roles of AhR, we studied AhR-1, the C. elegans ortholog and performed transcriptomic and metabolomic analysis respectively in neuronal cells expressing AhR-1 and in whole animals. Next, we designed a reporter system in order to investigate if the transcriptional activity of AhR-1 could be modulated. Cos-7 cells were transfected with AhR-1, its dimerization partner AhA-1 (C. elegans ARNT ortholog) and a Firefly luciferase gene under the control of the human cytochrome P450 1A1 promotor. The luciferase bioluminescence measurement allows the identification of C. elegans AhR-1 modulators. Transcriptional profiling in neurons expressing AhR-1 revealed 95 genes down-regulated, and 76 genes up-regulated in AhR-1 KO animals. These genes are associated with nervous system function (depleted) and fatty acid process, oxidative phosphorylation and glycolysis (enriched). Metabolomic profiling results indicate a role for AhR-1 in regulating several endogenous metabolic pathways: amino-acid metabolism, carbohydrate metabolism as well as fatty acid metabolism Then, with the COS-7 in vitro screening model, we identified positive and negative modulators such as bacterial, dietary or environmental compounds. Considering C. elegans environment, these results could be used to highlight the role of invertebrate AhR and identified new features in vertebrate AhR.
Project description:Purpose: To uncover immune genes and pathways that are modulated by the GPCR/NPR-15 during S. aureus infection Methods: RNA was extracted from synchronized L4 stage npr-15(tm12539) and WT animals grown at 20 C and infected with S. aureus for 8 hours, followed by Qiagen extraction kits and following standard methods Results: RNA seq analyses shows enriched and signficant upregulated immune, neuropeptide, synaptic signaling and metabolism genes and pathways that are dependent on NPR-15 Conclusions: Our study uncovered NPR-15 to be modulator of the innate immunity in C. elegans under infection