Plenefisch JD et al. (1994) Worm Breeder's Gazette "Cloning mua-3: Some Observations on the New Molecular Era"

Plenefisch JD, Hedgecock EM

[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

Parham C et al. (1994) Worm Breeder's Gazette "Tc4 and Tc5: What Makes Them Move and Why It Matters"

Beinhorn J, Collins JJ, Butze K, Parham C

[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

Almeida CA et al. (1994) Worm Breeder's Gazette "Function of a Domain of the Myosin Heavy Chain Implicated in Familial Hypertrophic Cardiomyopathy"

Collins JJ, Almeida CA, Swift KE

[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

Chalfie M (1993) J Neurobiol "Touch receptor development and function in Caenorhabditis elegans."

Chalfie M

[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.

Maine EM et al. (1994) Worm Breeder's Gazette "Mutations That Enhance glp-1 Identify Genes Required For Various Aspects of Germline Development."

Gelber MB, Smardon AM, Shu P, Qiao L, Maine EM, Lissemore JL

[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.

Chalfie M (1998) Nature "Genome sequencing. The worm revealed."

Chalfie M

[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

Latheef, Sharmilah L.J. et al. (2013) International Worm Meeting "The use of C.elegans to identify novel mutations that confer benzimidazole resistance."

Latheef, Sharmilah L.J., Gilleard, John S., Stasiuk, Susan S.

[International Worm Meeting, 2013]

Parasitic nematodes are a huge threat to the livestock industry as well as human health. Livestock infections cause billions of dollars in production loss per annum whilst infections in humans are a leading cause of disability and poverty especially in the developing world. Intensive use of the limited number of anthelmintics available for the treatment of parasitic nematode infections in livestock has resulted in the widespread development of resistance in many regions of the world. The recent increase in community-wide anthelmintic treatment programs in humans in the developing world-using the same drug classes used in livestock- is raising concerns of similar emergence of resistance in human parasites. Hence, there is an urgent need to understand the causal mechanisms of resistance and develop new diagnostic tests and control measures. Benzimidazoles (BZ) are an important drug class for both human and animal parasite control. It is known that amino acid substitutions in the isotype-1 b-tubulin drug target at positions 167, 198 and 200 can prevent drug binding and lead to drug resistance in several parasitic livestock species. The major objective of this project is to identify additional novel causal mutations of BZ resistance using the natural genetic variation found in wild C.elegans populations. The effect of albendazole on the motility of 16 natural C.elegans isolates was tested and two strains were identified that had a high level of resistance compared to the N2 strain. The ben-1 locus was sequenced in these two strains and a novel mutation resulting in an Alanine to Proline substitution at amino acid position 185 was found in one strain and a frame-shift in the other. The functional significance of the identified non-synonymous polymorphisms was confirmed by genetic complementation studies with the ben-1(e1880) reference strain. Hence, we have identified naturally occurring strains with a high level of resistance to BZ drugs which leads to questions regarding the role of environmental pollution as a selective force. We've also identified a previously unreported amino acid substitution in the ben-1 locus that is capable of conferring resistance which has yet to be reported in parasitic nematodes.

Hotez PJ et al. (1993) Parasitol Today "Hookworm larval infectivity, arrest and amphiparatenesis: the Caenorhabditis elegans Daf-c paradigm."

Hotez PJ, Schad GA, Hawdon JM

[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.

Stasiuk, Susan J et al. (2013) International Worm Meeting "Metabolism of benzimidazole anthelmintics in Caenorhabditis elegans, and the ruminant parasite, Haemonchus contortus."

Gilleard, John S, Ro, Dae-Qyun, Stasiuk, Susan J, MacNevin, Gillian

[International Worm Meeting, 2013]

Widespread anthelmintic resistance among animal parasites and concerns regarding its emergence among human parasites makes the understanding of how parasites metabolize and eliminate anthelmintics an important goal. We have previously shown that albendazole, an anthelmintic commonly used in humans and livestock, is metabolized to a glucoside derivative in C. elegans. Glycation of drugs is rare in mammals and had not been previously reported for the benzimidazoles. We have investigated whether other members of the benzimidazole (BZ) family were also glycosylated in C. elegans and in H. contortus, a parasitic nematode that is a model for anthelmintic drug discovery and resistance research. Using HPLC and LC/MS we have characterised the metabolites produced by C. elegans following exposure to albendazole, mebendazole, thiabendazole, oxfenbendazole, and fenbendazole. Each of the BZ were modified by the addition of a glucose ( plus or minus other) moiety. This glycation appears to be nematode specific, since mammals have been shown to metabolize these substances by sulfo-conjugation reactions only. Furthermore, the metabolites were found mainly in the media suggesting they are efficiently eliminated from the worms. We have shown that the parasite H. contortus metabolizes the BZs to the same glucoside derivatives as C. elegans. One approach to identifying the enzymes responsible for the metabolism is to examine the transcriptomic response. We have shown earlier that a small number of C. elegans genes are up-regulated in response to albendazole (including cyp-35C1, cyp-35A2, cyp-35A5, ugt-16, ugt-63 and gst-5). We have tested the specificity of this response using QRT-PCR and have found that these genes were up-regulated by the other BZs, although the relative levels of up-regulation differed between drugs. By manipulating the expression levels of these genes in C. elegans we will test the effect on BZ metabolism and potency. In summary, metabolism of BZs differ dramatically between mammals and nematodes but is very similar in C. elegans and H. contortus suggesting C. elegans is a valid model for the functional analysis of these processes in strongylid parasites.

Waterston RH et al. J Neurogenet "John Sulston (1942-2018): a personal perspective."

Waterston RH, Moerman DG

[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.