Line Elnif Thomsen et al. (2006) European Worm Meeting "Caenorhabditis elegans is a model host for Listeria monocytogenes"

Bente M. Jensen, Line Elnif Thomsen, Birgitte H. Kallipolitis, Nils J. Fargeman, Hanne Ingmer

[European Worm Meeting, 2006]

Line Elnif Thomsen1, Bente M. Jensen2, Nils J. Frgeman2, Birgitte H. Kallipolitis2 and Hanne Ingmer1. Several bacterial pathogens, both Gram-positive and Gram-negative, kill the nematode Caenorhabditis elegans when supplied as a food source, and a variety of bacterial virulence factors, known to play a role in mouse-models, have been shown also to play a role in nematode pathogenesis. The gram-positive facultative intracellular food-borne pathogen Listeria monocytogenes is associated with serious invasive infections in humans and animals. We have investigated the possibility of using C. elegans as a model to analyse the virulence of various L. monocytogenes strains. We found that L. monocytogenes kill C. elegans over the course of several days, as a consequence of an accumulation of bacteria in the worm intestine, and that there is an overlap between L. monocytogenes virulence factors required for mammalian and nematode pathogenesis. C. elegans is therefore an attractive model to study the virulence of this pathogen and potentially to identify new virulence factors and further work might reveal the genetic repertoire required for infection of the nematode by L. monocytogenes.

Zdraljevic, S. et al. (2017) International Worm Meeting "Multiple interacting loci contribute to topoisomerase II poison responses in Caenorhabditis elegans."

Kim, T.W., Cook, D.E., Andersen, E.C., Brady, S.C., Kameny, L.P., Hippleheuser, S.W., Zdraljevic, S.

[International Worm Meeting, 2017]

Interacting genetic and environmental factors influence responses to anti-neoplastic treatments causing large differences in efficacy among individuals in the human population. Understanding the causes of these population-wide differences is a critical step towards the elucidation of markers that are predictive of patient responses in the clinic to personalize treatments and improve existing medications. In an attempt to disentangle this complexity, we used an unbiased linkage mapping approach in Caenorhabditis elegans to identify genetic determinants underlying response to a broadly administered class of anti-neoplastic compounds that poison the activity of topoisomerase II (TOP-2) enzymes. We identified numerous quantitative trait loci (QTL) that explain phenotypic variation among a panel of recombinant inbred advanced intercross lines generated between the Bristol and Hawaiian strains in response to amsacrine, dactinomycin, and etoposide. Interestingly, multiple overlapping QTL located on the center of chromosome V explain phenotypic variation in response to these three poisons, suggesting a common mechanism underlying the responses to these compounds. We constructed reciprocal Bristol and Hawaiian near-isogenic lines (NILs) that encompass all six chrV QTL. Interestingly, these NILs only recapitulated the etoposide and dactinomycin QTL effects, but failed to recapitulate the amsacrine QTL effects. We used these NILs to generate 80 recombinant NILs with smaller introgressed regions to separate a possible amsacrine-specific multi-locus interaction within the NIL region and to narrow the QTL confidence intervals associated with responses to all three drugs. Phenotypic analysis of these sub-interval NILs isolated the two etoposide and dactinomycin-specific QTL within the original NIL region and uncoupled an amsacrine-specific incompatibility locus from an amsacrine-specific QTL. These results highlight the complexity of genetic factors that influence metazoan responses to anti-neoplastic compounds.

McGhee JD (1987) Biochemistry "Purification and characterization of a carboxylesterase from the intestine of the nematode Caenorhabditis elegans."

McGhee JD

[Biochemistry, 1987]

The major intestinal esterase from the nematode Caenorhabditis elegans has been purified to essential homogeneity. Starting from whole worms, the overall purification is 9000-fold with a 10% recovery of activity. The esterase is a single polypeptide chain of Mr 60,000 and is stoichiometrically inhibited by organophosphates. Substrate preferences and inhibition patterns classify the enzyme as a carboxylesterase (EC 3.1.1.1), but the physiological function is unknown. The sequence of 13 amino acid residues at the esterase N- terminus has been determined. This partial sequence shows a surprisingly high degree of similarity to the N-terminal sequence of two carboxylesterases recently isolated from Drosophila mojavensis [Pen, J., van Beeumen, J., & Beintema, J. J. (1986) Biochem. J. 238, 691-699].

Murakami S et al. (1999) Curr Biol "Life extension and stress resistance in Caenorhabditis elegans modulated by the tkr-1 gene."

Johnson TE, Murakami S

[Curr Biol, 1999]

In this Brief Communication, which appeared in the 14 September 1998 issue of Current Biology, the UV dose was reported erroneously. The dose reported was 20 J/m2 but the actual dose used was 0.4 J/cm2. Also, the gene formally referred to as tkr-1 has since been renamed old-1 (overexpression longevity determination).

Bernstein, Max et al. (2013) International Worm Meeting "The hunt for quantitative trait nucleotides: a near-isogenic line based approach in C. elegans."

Rockman, Matthew, Bernstein, Max

[International Worm Meeting, 2013]

The individual nucleotides responsible for phenotypic diversity have been very difficult to isolate. The majority of known causal variants that affect traits in wild populations of a species occur within protein-coding regions. These variants are typically of very large effect and may not be typical of the sorts of alleles that drive evolution. There are many confounding effects that can explain the relative lack of causal variants, or quantitative trait nucleotides (QTNs), particularly alleles of small effect, epistasis, and gene-environment interactions. One way to elucidate quantitative trait loci (QTLs) is through the creation of near-isogenic lines (NILs), where the majority of the genome (>95%) is of one genomic background. NILs have previously been created for the nematode C. elegans and identified QTLs across the genome for several phenotypes. C. elegans is a naturally inbred species, which makes it ideal for isolating QTNs. Starting with a NIL that harbors a ~1.5 Mb segment on Chromosome X originating from the Hawaiian isolate CB4856, we have created a series of more than 1000 sub-NILs that break up this segment into smaller regions by recombination. These sub-NILs will be genotyped at 278 SNPs within the 1.5 Mb segment. We are currently piloting high-throughput fitness assays similar to previous work by Elvin et al (2011) and Ramani et al (2012). Additionally, we plan to do gene expression analysis on a subset of the sub-NIL panel to characterize expression QTNs (eQTNs). QTL mapping on simulated sub-NIL datasets shows that for a single QTL model, we can accurately map small effect (h2<0.1) causal variants. Due to the linkage disequilibrium pattern in the sub-NIL panel, traditional QTL mapping methods are not applicable. We show that pairwise comparisons among groups of similar sub-NIL genotypes provide a systematic method for identifying QTLs. We have also modeled more complex QTL scenarios, including multiple QTLs and epistatic interactions. These simulations have informed us of our potential statistical power for future QTL mapping experiments.

Ramos CG et al. (2014) J Bacteriol "Retraction for Ramos et al., MtvR is a global small noncoding regulatory RNA in Burkholderia cenocepacia."

Feliciano JR, da Costa PJ, Ramos CG, Grilo AM, Leitao JH

[J Bacteriol, 2014]

Volume 195, no. 16, p. 35143523, 2013. A number of problems related to images published in this paper have been brought to our attention. Figure 1D contains duplicated images in lanes S and LE, and Fig. 4D and 6B contain images previously published in articles in this journal and in Microbiology and Microbial Pathogenesis, i.e., the following: C. G. Ramos, S. A. Sousa, A. M. Grilo, J. R. Feliciano, and J. H. Leitao, J. Bacteriol. 193:15151526, 2011. doi:10.1128/JB.01374-11. S. A. Sousa, C. G. Ramos, L. M. Moreira, and J. H. Leitao, Microbiology 156:896908, 2010. doi:10.1099/mic.0.035139-0. C. G. Ramos, S. A. Sousa, A. M. Grilo, L. Eberl, and J. H. Leitao, Microb. Pathog. 48:168177, 2010. doi: 10.1016/j.micpath.2010.02.006. Therefore, we retract the paper. We deeply regret this situation and apologize for any inconvenience to the editors and readers of Journal of Bacteriology, Microbial Pathogenesis, and Microbiology.

Nillegoda NB et al. (2015) Nature "Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation."

Berynskyy M, Morimoto RI, Bukau B, Stengel F, Kirstein J, Szlachcic A, Arnsburg K, Stank A, Scior A, Nillegoda NB, Gao X, Guilbride DL, Aebersold R, Wade RC, Mayer MP

[Nature, 2015]

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states. Healthy metazoan cells effectively eliminate intracellular protein aggregates, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro. This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control.

Montgomery, Jordan et al. (2015) International Worm Meeting "Genetic mapping of hybrid developmental delay with novel near-isogenic lines of Caenorhabditis briggsae."

Montgomery, Jordan, Ross, Joseph

[International Worm Meeting, 2015]

When two organisms are able to reproduce, but their hybrid offspring exhibit reduced fitness, this is often evidence of the onset of speciation. Such hybrid incompatibility is a result of genetic differences between the parental populations. C. briggsae is a useful system for studying the onset of speciation because of its unique and distinct phylogeographic population structure. C. briggsae is also well suited for speciation studies because of empirical evidence suggesting that genetic differences between populations result in reduced hybrid fitness. For example, previous studies have shown that approximately 20% of F2 offspring from an AF16-HK104 cross exhibit a developmental delay phenotype. This phenotype is associated with homozygosity of AF16 alleles near the middle of chromosome III. Identifying the genetic basis of this hybrid dysfunction phenotype will aid in the identification of the genetic basis of a putative speciation event. To achieve this goal, we created a panel of replicate near-isogenic lines (NILs), with AF16 alleles on chromosome III introgressed onto the HK104 background.By comparing genotypes of the NILs able to produce developmentally delayed offspring with those that cannot, we propose that the locus on chromosome III partly responsible for the epistatic interaction producing the delay phenotype exists between 4.271 and 5.649 Mbp. Future studies will focus on high-resolution genotyping of the NILs, followed by fine-mapping and candidate gene approaches to identifying the molecular basis of this trait. Ultimately, these results assist in better understanding the evolutionary forces and genetic mechanisms driving speciation events.

Miller DM et al. (1992) Worm Breeder's Gazette "unc-4 LacZ Expression in A-Type Motor Neurons"

Miller DM, Niemeyer CJ

[Worm Breeder's Gazette, 1992]

unc-4 LacZ expression in A-type motor neurons David M. Miller and Charles J. Niemeyer, Dept. of Cell Biology, Duke Univ. Medical Ctr, Durham, NC 27710

Sommer RJ et al. (1994) Worm Breeder's Gazette "Evolution of Vulva-Formation: Part II: Species With a Central Vulva"

Sommer RJ, Sternberg PW

[Worm Breeder's Gazette, 1994]

Evolution of vulva-formation: Part II: Species with a central vulva Ralf J. Sommer & Paul W. Sternberg, California Institute of Technology, Division of Biology 156-29, Pasadena, CA 91125