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  1. Article ; Online: Protocol for transgenerational learned pathogen avoidance behavior assays in Caenorhabditis elegans

    Rebecca S. Moore / Rachel Kaletsky / Coleen T. Murphy

    STAR Protocols, Vol 2, Iss 1, Pp 100384- (2021)

    2021  

    Abstract: Summary: Animal experiences, including learned behaviors, can be passed down to several generations of progeny in a phenomenon known as transgenerational epigenetic inheritance. Yet, little is known regarding the molecular mechanisms regulating ... ...

    Abstract Summary: Animal experiences, including learned behaviors, can be passed down to several generations of progeny in a phenomenon known as transgenerational epigenetic inheritance. Yet, little is known regarding the molecular mechanisms regulating physiologically relevant transgenerational memories. Here, we present a method for Caenorhabditis elegans in which worms learn to avoid the pathogen Pseudomonas aeruginosa (PA14). Unlike previous protocols, this training paradigm, either using PA14 lawns or through exposure to a PA14 small RNA (P11), induces memory in four generations of progeny.For complete details on the use and execution of this protocol, please refer to Moore et al. (2019) and Kaletsky et al. (2020).
    Keywords Genetics ; Model organisms ; Science (General) ; Q1-390
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Nervous system-wide profiling of presynaptic mRNAs reveals regulators of associative memory

    Rachel N. Arey / Rachel Kaletsky / Coleen T. Murphy

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 11

    Abstract: Abstract Presynaptic protein synthesis is important in the adult central nervous system; however, the nervous system-wide set of mRNAs localized to presynaptic areas has yet to be identified in any organism. Here we differentially labeled somatic and ... ...

    Abstract Abstract Presynaptic protein synthesis is important in the adult central nervous system; however, the nervous system-wide set of mRNAs localized to presynaptic areas has yet to be identified in any organism. Here we differentially labeled somatic and synaptic compartments in adult C. elegans with fluorescent proteins, and isolated synaptic and somatic regions from the same population of animals. We used this technique to determine the nervous system-wide presynaptic transcriptome by deep sequencing. Analysis of the synaptic transcriptome reveals that synaptic transcripts are predicted to have specialized functions in neurons. Differential expression analysis identified 542 genes enriched in synaptic regions relative to somatic regions, with synaptic functions conserved in higher organisms. We find that mRNAs for pumilio RNA-binding proteins are abundant in synaptic regions, which we confirmed through high-sensitivity in situ hybridization. Presynaptic PUMILIOs regulate associative memory. Our approach enables the identification of new mechanisms that regulate synaptic function and behavior.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates

    Salman Sohrabi / Danielle E. Mor / Rachel Kaletsky / William Keyes / Coleen T. Murphy

    Communications Biology, Vol 4, Iss 1, Pp 1-

    2021  Volume 9

    Abstract: Salman Sohrabi et al. develop an automated, high-throughput assay to study spasm-like curling behavior in C. elegans, which is related to motor control symptoms in Parkinson’s disease. They apply this screening approach to identify four candidate drugs ... ...

    Abstract Salman Sohrabi et al. develop an automated, high-throughput assay to study spasm-like curling behavior in C. elegans, which is related to motor control symptoms in Parkinson’s disease. They apply this screening approach to identify four candidate drugs for potential late-in-life interventions for Parkinson’s disease.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: GAIT-GM integrative cross-omics analyses reveal cholinergic defects in a C. elegans model of Parkinson’s disease

    Lauren M. McIntyre / Francisco Huertas / Alison M. Morse / Rachel Kaletsky / Coleen T. Murphy / Vrinda Kalia / Gary W. Miller / Olexander Moskalenko / Ana Conesa / Danielle E. Mor

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 9

    Abstract: Abstract Parkinson’s disease (PD) is a disabling neurodegenerative disorder in which multiple cell types, including dopaminergic and cholinergic neurons, are affected. The mechanisms of neurodegeneration in PD are not fully understood, limiting the ... ...

    Abstract Abstract Parkinson’s disease (PD) is a disabling neurodegenerative disorder in which multiple cell types, including dopaminergic and cholinergic neurons, are affected. The mechanisms of neurodegeneration in PD are not fully understood, limiting the development of therapies directed at disease-relevant molecular targets. C. elegans is a genetically tractable model system that can be used to disentangle disease mechanisms in complex diseases such as PD. Such mechanisms can be studied combining high-throughput molecular profiling technologies such as transcriptomics and metabolomics. However, the integrative analysis of multi-omics data in order to unravel disease mechanisms is a challenging task without advanced bioinformatics training. Galaxy, a widely-used resource for enabling bioinformatics analysis by the broad scientific community, has poor representation of multi-omics integration pipelines. We present the integrative analysis of gene expression and metabolite levels of a C. elegans PD model using GAIT-GM, a new Galaxy tool for multi-omics data analysis. Using GAIT-GM, we discovered an association between branched-chain amino acid metabolism and cholinergic neurons in the C. elegans PD model. An independent follow-up experiment uncovered cholinergic neurodegeneration in the C. elegans model that is consistent with cholinergic cell loss observed in PD. GAIT-GM is an easy to use Galaxy-based tool for generating novel testable hypotheses of disease mechanisms involving gene-metabolite relationships.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans

    Heehwa G. Son / Mihwa Seo / Seokjin Ham / Wooseon Hwang / Dongyeop Lee / Seon Woo A. An / Murat Artan / Keunhee Seo / Rachel Kaletsky / Rachel N. Arey / Youngjae Ryu / Chang Man Ha / Yoon Ki Kim / Coleen T. Murphy / Tae-Young Roh / Hong Gil Nam / Seung-Jae V. Lee

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 11

    Abstract: The decline of DNA and protein quality control contributes to organismal ageing. Here, Sonet al. report that nonsense-mediated mRNA decay, a RNA quality control mechanism, is enhanced in long-lived daf-2 mutant worms and contributes to their longevity by ...

    Abstract The decline of DNA and protein quality control contributes to organismal ageing. Here, Sonet al. report that nonsense-mediated mRNA decay, a RNA quality control mechanism, is enhanced in long-lived daf-2 mutant worms and contributes to their longevity by regulating expression of the yars-2/tyrosyl tRNA synthetase.
    Keywords Science ; Q
    Language English
    Publishing date 2017-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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