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[
International Worm Meeting,
2017]
Caenorhabditis elegans is used as a model in over 1,100 labs around the world and has enabled biological discoveries in many diverse fields. These advances have been fueled by an extensive genetic toolkit, including strains, reagents, and databases. However, the majority of C. elegans research focuses on the laboratory-domesticated N2 strain, neglecting potential insights gleaned from natural populations. Studies of C. elegans natural variation can identify the genetic factors underlying biomedically relevant traits and genome evolution. To address the need for resources to study natural variation, we developed the Caenorhabditis elegans Natural Diversity Resource (CeNDR) - available at www.elegansvariation.org. The web-based CeNDR platform includes three areas: (1) a central repository for the deposition, organization, and dissemination of wild C. elegans strains, including detailed information for each strain (e.g. collection date, GPS location, substrate, and elevation); (2) a data portal for dissemination of whole-genome sequence data in BAM or CRAM formats and variant data in VCF format for each of the 383 wild isolates, including a powerful interactive genome browser that can be used to interrogate genetic variation across the population for genes or regions of interest; (3) a genome-wide association mapping portal to enable mappings of quantitative traits measured using wild C. elegans strains, including a comprehensive report of significance, variation, measures of selection, etc. We believe that CeNDR will become an indispensable tool within the C. elegans genetic toolkit to enable researchers to examine natural populations and identify interesting new biological phenomena.
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[
Development,
2024]
The mitotic kinase Aurora A has been shown to regulate the anterior-posterior polarity in developing Caenorhabditis elegans embryos. In a new study, Daniel Dickinson and colleagues find that Aurora A has temporally distinct roles in coordinating the localization of Partitioning defective (PAR) proteins to establish cell polarity during development. To find out more about the story behind the paper, we caught up with first author Nadia Manzi and corresponding author Daniel Dickinson, Assistant Professor at the University of Texas at Austin.
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[
MicroPubl Biol,
2022]
Chemotaxis assays are used extensively to study behavioral responses of Caenorhabditis nematodes to environmental cues. These assays result in a chemotaxis index (CI) that denotes the behavioral response of a population of nematodes to a particular compound and can range from 1 (maximum attraction) to -1 (maximum avoidance). Traditional chemotaxis assays have low throughput because researchers must manually setup experimental populations and score CIs. Here, we describe an automated methodology that increases throughput by using liquid-handling robots to setup experimental populations and a custom image analysis package, ct, to automate the scoring of CIs from plate images.
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[
J Fr Ophtalmol,
1991]
A new case of conjunctival allergic nodule is reported in a Guinean man. This lesion was first described by Ashton and Cook in 1979. Histologically, this nodule consists of amorphous eosinophilic material surrounded by epithelioid and giant cells arranged in a pallisade; some eosinophils are often found in the inflammatory reaction. This lesion usually resolves spontaneously. In documented cases, nematodes and particularly filaria such as Mansonella perstans are usually isolated. Our observation is the first documented case with Onchocerca volvulus. Microfilariae were detected by examination of normal saline containing the biopsy specimen. The new major antifilarial treatment ivermectin was associated.
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[
Development,
2019]
Animal cytokinesis is driven by an actomyosin ring that assembles at the cell equator and constricts to physically separate the two daughters. Although myosin is known to be essential for cytokinesis in multiple systems, whether this requirement reflects its motor or actin crosslinking activities has recently been a matter of contention. A new paper in Development now addresses this problem using the first divisions of the <i>Caenorhabditis elegans</i> embryo as a model. We caught up with the paper's three first authors Daniel Osorio, Elaine Chan and Joana Saramago, and their supervisor Ana Carvalho, Principal Investigator at the University of Porto's
i3S consortium, to find out more about the story.
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Cook, Daniel, Lee, Daehan, Paik, Young-Ki, Lee, Junho, Andersen, Erik, Kim, Heekyeong, Yang, Heeseung
[
International Worm Meeting,
2021]
Dispersal is crucial for many organisms. There are various strategies for efficient dispersal, and phoresy is one example. Animals can disperse efficiently by attaching to another organism, like hitchhiking. Caenorhabditis elegans dauers show a stage-specific standing behavior, called nictation, that can facilitate phoretic interactions of dauers. Standing and waving their body, dauers can interact with other organisms such as isopods. It helps dauers to escape from harsh conditions and move into a better environment for re-growing and reproduction. As C. elegans are found most frequently as dauer larvae in the wild, nictation is thought to play an important role in their life cycle. However, the genetic basis and the underlying regulatory mechanism of nictation are not well understood. Here, we try to figure out the genetic factors that regulate nictation and make nictation diversity between C. elegans wild isolates. Wild isolates from the worldwide region showed diverse nictation fractions in the same experimental conditions. A genome-wide association mapping of the nictation of 137 wild isolates identified a quantitative trait locus (QTL) for nictation. Using near-isogenic lines, we identified a QTL of 90 kb interval, and also found that this QTL affects other dauer-related phenotypes. Now we are testing and confirming candidate genes using CRISPR mutants and RNAi experiments. Elucidating nictation regulatory mechanisms will provide new insights into the genetic basis of phoretic behavior.
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Lee, Junho, Zdraljevic, Stefan, Andersen, Erik, Rodriguez, Briana, Lee, Daehan, Tanny, Robyn, Cook, Daniel, Brady, Shannon, Zamanian, M
[
International Worm Meeting,
2017]
Parasitic nematodes impose a debilitating health and economic burden across much of the world. The morbidity and mortality inflicted by these pathogens are partly curtailed by mass drug administration programs that depend on the continued efficacy of a limited portfolio of anthelmintic drugs. Benzimidazoles are WHO-designated "Essential Medicines" and an indispensable component of this limited arsenal. Nematode resistance to benzimidazole chemotherapy threatens parasite control efforts in both human and veterinary medicine. Despite this threat, the genetic landscape of potential resistance mechanisms to thiscritical drug class remains largely unexplored. There is an urgent and recognized need to identify molecular mechanisms and genetic markers that cause benzimidazole resistance. In order to identify conserved nematode drug responses, we exploit natural variation in two model roundworms, Caenorhabditis elegans and Caenorhabditis briggsae, to discover quantitative trait loci (QTL) that control benzimidazole sensitivity. Surprisingly, we found that resistance to benzimidazoles mapped to syntenic piRNA-enriched regions of the genome with few protein-coding genes in both Caenorhabditis species. We used near isogenic lines (NILs) to narrow the major-effect benzimidazole QTL in C. elegans to a smaller region of the genome and demonstrate that the benzimidazole-resistance phenotype results from piRNA variation that is dependent on the function of the piRNA-associated argonaute
prg-1. We identified candidate piRNAs causal to the resistance phenotype and putative genes targeted for silencing by downstream 22G RNAs. Our results indicate that small RNAs require consideration in drug resistance mechanisms in nematodes, because the piRNA pathway and related small RNA pathways are conserved in many medically and agriculturally important parasitic nematodes. Importantly, this resistance mechanism could be mediated through the heritable transgenerational effects of small RNAs. This finding has significant implications for parasite control and the management of drug resistance in other phyla and systems.
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[
Autophagy,
2024]
Professor Richard (Rick) Morimoto is the Bill and Gayle Cook Professor of Biology and Director of the Rice Institute for Biomedical Research at Northwestern University. He has made foundational contributions to our understanding of how cells respond to various stresses, and the role played in those responses by chaperones. Working across a variety of experimental models, from <i>C</i>. <i>elegans</i> to human neuronal cells, he has identified a number of important molecular components that sense and respond to stress, and he has dissected how stress alters cellular and organismal physiology. Together with colleagues, Professor Morimoto has coined the term "proteostasis" to signify the homeostatic control of protein expression and function, and in recent years he has been one of the leaders of a consortium trying to understand proteostasis in healthy and disease states. I took the opportunity to talk with Professor Morimoto about proteostasis in general, the aims of the consortium, and how autophagy is playing an important role in their research effort.
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[
MicroPubl Biol,
2021]
The AID system has emerged as a powerful tool to conditionally deplete proteins in a wide-range of organisms and cell types (Nishimura et al. 2009; Holland et al. 2012; Zhang et al. 2015; Natsume et al. 2016; Trost et al. 2016; Brown et al. 2017; Daniel et al. 2018; Chen et al. 2018; Camlin and Evans 2019). The system is comprised of two components. A plant F-box protein Transport Inhibitor Response 1 (TIR1) is expressed and forms a complex with endogenous Skp1 and Cul1 proteins to form a functional SCF ubiquitin ligase (Nishimura et al. 2009; Natsume and Kanemaki 2017). TIR1 can either be expressed constitutively or in a tissue-specific manner depending on promoter choice. A degron sequence from the IAA17 protein is fused to the protein of interest (Nishimura et al. 2009; Natsume and Kanemaki 2017). Commonly used auxin-inducible degrons include 44 amino acid (AID*) and 68 amino acid (mAID) fragments of IAA17 (Morawska and Ulrich 2013; Li et al. 2019). Addition of the plant hormone auxin bridges an interaction between TIR1 and the degron and the SCF ligase ubiquitylates the degron-fused protein leading to proteasomal degradation.
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Stevens, Lewis, Buchanan, Claire, Andersen, Erik, Stinson, Loraina, Dilks, Clayton, Tanny, Robyn, Lu, Dan, Zhang, Gaotian, Evans, Kathryn, Zdraljevic, Stefan, Crombie, Tim, Lee, Daehan, Roberto, Nicole, Wang, Ye, Cook, Daniel
[
International Worm Meeting,
2021]
Caenorhabditis elegans isolated from the Hawaiian Islands are known to harbor a high degree of genetic diversity relative to non-Hawaiian isolates. It was recently suggested that Hawaiian C. elegans can be partitioned into at least four genetically distinct groups. An analysis of geospatial environmental data further suggested that the genetic groups might associate with environmental parameters such as elevation and temperature, although the sample size for that study was small (n = 43 isolates). To better characterize the niche and genetic diversity of Hawaiian C. elegans and further define the associations of genetic groups with environmental parameters, we sampled different substrates and niches across the Hawaiian Islands six times over a three-year period. In total, we isolated 7,107 nematodes from 2,400 of 4,506 substrate samples (53% success rate). Among the nematodes we isolated, we identified five Caenorhabditis species, including 499 C. elegans, 377 C. briggsae, and 55 C. tropicalis isolates. We measured several environmental parameters at each sampling site and combined them with environmental parameters from geospatial databases to reveal that C. elegans is typically found in cooler and relatively drier climates at higher elevation than the other two selfing Caenorhabditis species. We isolated C. elegans most frequently from montane-alpine mesic forest habitat dominated by plant species native to the Hawaiian Islands. When possible, we cryopreserved C. elegans isolates and sequenced their genomes. To date, including Hawaiian isolates from collaborators, we have sequenced the genomes of 505 Hawaiian C. elegans isolates. With these data, we grouped the isolates into 163 isotypes (strains belonging to a single isotype have >0.9997 genome-wide concordance). We found that some of the isotypes were collected from the same locations over the three-year sampling period, and most of the collections of the same isotype were found within 500 meters of each other. Principal component analysis (PCA) of genetic variation revealed that the 163 isotypes fall into seven genetically distinct groups, three more than previously found on the islands with a smaller sample. Taken together, our findings begin to outline the spatiotemporal patterns of C. elegans genetic diversity on the Hawaiian Islands and raise new questions about evolutionary forces driving the genetic structure we have uncovered. For example, are these groups isolated by ecological or geographic distances, or perhaps both, and to what extent do reproductive incompatibilities contribute to the structure we have observed?