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[
Worm Breeder's Gazette,
1994]
Cloning
mua-3: some observations on the new Molecular Era John Plenefisch and Edward Hedgecock, Dept. of Biology, Johns Hopkins University, Baltimore MD 21218
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[
Worm Breeder's Gazette,
1994]
Tc4 and Tc5: what makes them move and why it matters Christi Parham, Kristie Butze, Joanna Beinhorn and John Collins. Dept. of Biochemistry and Molecular Biology, University of New Hampshire. Durham, NH 03824
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[
Worm Breeder's Gazette,
1994]
Function of a Domain of the Myosin Heavy Chain Implicated in Familial Hypertrophic Cardiomyopathy Craig A. Almeida, Kerry E. Swift and John J. Collins Department of Biochemistry and Molecular, University of New Hampshire, Durham, NH 03820
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[
J Neurobiol,
1993]
Mutations causing a touch-insensitive phenotype in the nematode Caenorhabditis elegans have been the basis of studies on the specification of neuronal cell fate, inherited neurodegeneration, and the molecular nature of mechanosensory transduction. (C) 1993 John Wiley & sons, Inc.
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[
International Worm Meeting,
2015]
More than 2 billion people world-wide are estimated to be infected with parasitic nematodes, resulting in major economic and personal impacts from the years of life lost to poor health and premature mortality. The identification of drugs that can cheaply and effectively treat parasitic nematode infections is a critical global health need. However, the journey from initial drug development to approval for use in humans is long and costly, and screening directly on parasitic nematodes has intrinsic difficulties caused by the requirements for culturing and maintaining populations of parasites. It is likely that compounds that kill C. elegans will also kill parasitic nematodes, making C. elegans a cost-effective and rapid screening tool to identify new anthelmintics. To expedite the identification of drugs that can be rapidly translated into clinical use for parasite treatment, we are screening commercially available libraries of drugs approved for use in humans. These libraries represent drugs with known safety, bioavailability, and dosage information for use in humans that can be rapidly repurposed for treatment of parasitic nematode infections. Initial library screening has identified 92 compounds that kill C. elegans. These include known anthelmintics (Mebendazole, Pyrvinium pamoate, Tiabendazole, Niridazole, Levamisole, Pentamidine isethionate, Fenbendazole, Avermectin B1), as well as unexpected hits such as anti-Parkinsonian drugs. Numerous therapeutic groups are represented in the hits, including analgesics, antibacterial agents, antidepressants, antifungals, antihistamines, and antipsychotics. Continued testing will select for agents that are effective against multiple life stages (embryos, larval, dauer, and adult). Candidates will also be screened against databases of existing information to select agents with oral bioavailability, few side-effects in humans, and low cost for production. Compounds meeting these criteria will be given preference for follow-up testing. Our preliminary results indicate C. elegans may represent a powerful surrogate for large scale anti-nematode drug screening.
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[
International Worm Meeting,
2015]
Accumulation of the protein TDP-43 in neuronal aggregates is the major pathological feature of two devastating neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTLD-TDP). TDP-43 is an essential protein and is involved in many aspects of RNA metabolism from transcription to translation, although its most critical contribution may be regulation of the majority of cellular mRNA splicing events. Disruption of the normal activity of TDP-43, either by mutation of TDP-43 or alterations in TDP-43 regulatory pathways, promotes neuronal dysfuction and degeneration in a variety of model systems including C. elegans, Drosophila, zebrafish, mammalian cell culture, and mice. To study the cellular, molecular, and genetic underpinnings of TDP-43 mediated neurotoxicity in a tractable model system, we have developed C. elegans models of TDP-43 proteinopathy expressing either wild type or disease-causing mutant TDP-43 pan-neuronally (TDP-43 tg). These transgenic animals display early, progressive motor dysfunction, decreased lifespan, and age-dependent degeneration of specific types of neurons, including GABA-ergic and dopaminergic neurons (1). However, not all TDP-43 expressing neurons undergo apparent neurodegeneration, indicating differences in sensitivities of specific populations of neurons to the presence of TDP-43. Surveying the range of responses to TDP-43 may provide a set of shared characteristics for populations of neurons susceptible or resistant to aberrant TDP-43. To investigate neuronal function in TDP-43 tg animals, we are utilizing a panel of behavioral, stress response, and stress survival assays. Results from these assays have identified individual sensory neurons with functional impairments in the absence of early neuronal cell body degeneration. These TDP-43 sensitive neurons will allow dissection of the effects of neurotoxic TDP-43 on neuronal function, and provide insight into the upstream processes leading to TDP-43 dependent neurodegeneration. 1. N. F. Liachko, C. R. Guthrie, B. C. Kraemer, Phosphorylation Promotes Neurotoxicity in a Caenorhabditis elegans Model of TDP-43 Proteinopathy. J Neurosci 30, 16208-16219 (2010).
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[
Worm Breeder's Gazette,
1994]
Mutations that enhance
glp-1 identify genes required for various aspects of germline development. Eleanor Maine, Li Qiao, Jim Lissemore-, Pei Shu, Anne Smardon, and Melanie Gelber. Biology Dept., Syracuse University, Syracuse, NY 13244 and Biology Dept., John Carroll University, Cleveland, OH 44118.
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[
Nature,
1998]
In 1983, John Sulston and Alan Coulson began to construct a complete physical map of the genome of the nematode worm Caenorhabditis elegans, and started what became known as the C. elegans Genome Project. At the time, several people wondered why John, who had just described all of the cell divisions in C. elegans (the cell lineage), was interested in this project rather than in a more 'biological' problem. He replied by joking that he had a "weakness for grandiose, meaningless projects". In 1989, as the physical map approached completion, the Genome Project, now including Bob Waterston and his group, embarked on the even more ambitious goal of obtaining the complete genomic sequence
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[
Parasitol Today,
1993]
Arrested development dramatically alters the life history of some species of soil-transmitted nematodes and elicits profound variations in the epidemiology of the infections they cause. Here, Peter Hotez, John Hawdon and Gerhard Schad show how an understanding of the cellular and molecular bases of arrested development may lead to new approaches for the control of ancylostomiasis and related infections.
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[
J Neurogenet
]
John Sulston changed the way we do science, not once, but three times - initially with the complete cell lineage of the nematode <i>Caenorhabditis elegans</i>, next with completion of the genome sequences of the worm and human genomes and finally with his strong and active advocacy for open data sharing. His contributions were widely recognized and in 2002 he received the Nobel Prize in Physiology and Medicine.