Curtis D (1994) Bioessays "Translational repression as a conserved mechanism for the regulation of embryonic polarity."

Curtis D

[Bioessays, 1994]

The mechanisms used to establish embryonic polarity are still largely unknown. A recent paper((1)) describes the expression pattern of the gene glp-1, which is required for induction events during development of the nematode Caenorhabditis elegans. Although glg-1 RNA is found throughout the early embryo, Glp-1 protein is only expressed in anterior cells. This negative translational regulation in posterior cells is shown to be mediated through sequences in the glp-1 3'untranslated region (3'UTR). Thus in nematodes, as in Drosophila, translational repression is one mechanism used to establish the embryonic anterior-posterior axis.

Asif, Muhammad Zaka et al. (2021) MicroPubl Biol

Van der Gaag, Victoria L., Edison, Arthur S., Muzio, Cole J., Asif, Muhammad Zaka, Nocilla, Kelsey A., Guo, Jane

[MicroPubl Biol, 2021]

1-Hydroxyphenazine (1-HP) is a small molecule produced by Pseudomonas aeruginosa, a bacterium that is used for pathogenesis models in C. elegans (Cezairliyan et al., 2013; Mahajan-Miklos, Tan, Rahme, & Ausubel, 1999). 1-HP is an especially interesting toxin to study as it has been shown to interact with human cells causing ciliary-slowing associated with dyskinesia and ciliostasis (Wilson et al., 1987). Prior research in our lab has shown that this molecule is toxic to C. elegans, with an LD50 between 150 and 200 M, but C. elegans can glycosylate 1-HP, which detoxifies the molecule (Stupp et al., 2013).

Campbell HD et al. (1993) Proc Natl Acad Sci U S A "The Drosophila melanogaster flightless-I gene involved in gastrulation and muscle degeneration encodes gelsolin-like and leucine-rich repeat domains and is conserved in Caenorhabditis elegans and humans."

Campbell HD, Kasprzak AB, Ozsarac N, Cotsell JN, Miklos GLG, Claudianos C, Schimansky T, Young IG, de Couet HG

[Proc Natl Acad Sci U S A, 1993]

Mutations at the flightless-I locus (fliI) of Drosophila melanogaster cause flightlessness or, when severe, incomplete cellularization during early embryogenesis, with subsequent abnormalities in mesoderm invagination and in gastrulation. After chromosome walking, deficiency mapping, and transgenic analysis, we have isolated and characterized flightless-I cDNAs, enabling prediction of the complete amino acid sequence of the 1256-residue protein. Data base searches revealed a homologous gene in Caenorhabditis elegans, and we have isolated and characterized corresponding cDNAs. By using the polymerase chain reaction with nested sets of degenerate oligonucleotide primers based on conserved regions of the C. elegans and D. melanogaster proteins, we have cloned a homologous human cDNA. The predicted C. elegans and human proteins are, respectively, 49and 58-134223489dentical to the D. melanogaster protein. The predicted proteins have significant sequence similarity to the actin-binding protein gelsolin and related proteins and, in addition, have an N-terminal domain consisting of a repetitive amphipathic leucine-rich motif. This repeat is found in D. melanogaster, Saccharomyces cerevisiae, and mammalian proteins known to be involved in cell adhesion and in binding to other proteins. The structure of the maternally expressed flightless-I protein suggests that it may play a key role in embryonic cellularization by interacting with both the cytoskeleton and other cellular components. The presence of a highly conserved homologue in nematodes, flies, and humans is indicative of a fundamental role for this protein in many metazoans.

Rubin GM et al. (2000) Science "Comparative genomics of the eukaryotes."

Ashburner M, Boguski MS, Miklos GLG, Brody T, Hariharan IK, Wortman JR, Birney E, Rubin GM, Fleischmann W, Fortini ME, Nelson CR, Brokstein P -COMMENT et al, Misra S, Cherry JM, Li PW, Yandell MD, Apweiler R, Henikoff S, Skupski MP

[Science, 2000]

A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.

Mirza, Z. et al. (2019) International Worm Meeting "Developmental slowing of Caenorhabditis elegans larvae on Pseudomonas aeruginosa strain CF18."

Ambros, V. R., Walhout, A. J. M., Mirza, Z.

[International Worm Meeting, 2019]

The development of Caenorhabditis elegans is very robust and it takes two days to reach adulthood under standard laboratory conditions. However, in the wild, developing animals face many challenges that are not necessarily present in a sterile and controlled laboratory environment, such as pathogen stress and dietary limitations. We investigated how development is influenced by pathogen stress using C. elegans larvae and 35 Pseudomonas aeruginosa strains under modified slow-killing conditions. We observed that C. elegans larvae exhibit three developmental phenotypes when fed with different P. aeruginosa strains: normal development, slow development and very slow development. Normal and slow development are classified as reaching adulthood in 2 days and 3 days, respectively; the third group causes extreme developmental slowing and P. aeruginosa strain CF18 fed larvae do not reach adulthood. To determine the mechanism of very slow development caused by CF18, we investigated three possible mechanisms: larval gut colonization status, bacterial nutrient deficiencies and pathogenesis/toxins1,2. We found that the larva's gut is not colonized by CF18. The larvae were able to reach adulthood on UV radiated CF18 lawn, suggesting that it is not nutrient deficiency but the pathogenicity of the strain that causes this developmental slowing. Secreted compounds by CF18 in the medium were also required for the very slow development phenotype. To determine the bacterial effectors causing this developmental delay, we have generated a transposon insertion library in the CF18 background and examined the developmental phenotype of larvae when fed with these mutants. We have found that transposon insertion in certain bacterial genes, including quorum sensing and two-component system genes, allow C. elegans larvae to overcome developmental slowing. 1. Tan, M.-W., Mahajan-Miklos, S. & Ausubel, F. M. Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc. Natl. Acad. Sci. 96, 715-720 (1999). 2. Watson, E. et al. Interspecies systems biology uncovers metabolites affecting C. elegans gene expression and life history traits. Cell 156, 759-770 (2014).

G Alloing et al. (1999) International C. elegans Meeting "Analysis of C. elegans host defense response to bacterial pathogen Pseudomonas aeruginosa"

M Tan, S Mahajan-Miklos, FM Ausubel, R Feinbaum, G Alloing

[International C. elegans Meeting, 1999]

Pathogenic bacteria are one of the major causes of disease in both animals and plants. Despite the specificity of the interaction between a bacterial pathogen and its host, there appear to be a number of common mechanisms underlying the process of disease (1,2). On the host side, it has been demonstrated that plants and animals share a set of defense mechanisms involved in "innate immunity". A signal transduction pathway with similarity to the Drosophila developmental regulatory Toll pathway appears to be critical for innate immunity in flies, mammals and plants (1). The underlying similarities between host/bacterial pathogen interactions suggested that a genetically tractable host/pathogen model could greatly improve our understanding of bacterial diseases in mammalian systems. A host/pathogen model system has been developed utilizing C. elegans and PA14, a clinical isolate of P. aeruginosa that is also virulent in Arabidopsis and mouse models. Depending on the medium used for bacterial growth, PA14 kills worms within 24 hours (Fast Killing or FK) or after a few days (Slow Killing or SK). FK is mediated at least in part by diffusible toxins whereas SK requires an infection-like process (3,4). Characterization of several PA14 mutants that are less pathogenic showed that the two killing processes require different bacterial virulence factors. We are interested in understanding the host response to infection by PA14. Towards this end, we have identified the C. elegans homologs of the Drosophila Toll receptor and Pelle kinase and are studying the role of these proteins in response to PA14 in both FK and SK. In addition, six C. elegans mutants have been isolated that are resistant to FK. We are beginning to map and characterize these mutants. (1) Belvin M.P. and Anderson K.V. (1996) Ann. Rev. Cell Dev. Biol. 12 , 393-416 (2) Finlay B.B and S. Falkow, S. (1997). Mol. Biol. Microbiol. Rev. 61 , 136-169 (3) Mahajan-Miklos, S. et al (1999). Cell 96 , 47-56 (4) Tan, M.-W. et al (1999). PNAS 96 , p715-720

JA Sheps et al. (1999) International C. elegans Meeting "Global analysis of ABC transporters in C. elegans"

V Ling, M Yeung Chau, DL Baillie, JA Sheps

[International C. elegans Meeting, 1999]

ABC transporters are a group of ATP Binding Cassette proteins highly conserved through all kingdoms of life. ABC transporters may be grouped into several distinct structural classes on the basis of amino acid sequence and domain organisation. ABC transporters play a role in the high level of resistance of C. elegans to a wide range of environmental toxins. Among these is the P-glycoprotein (Pgp) subclass, whose members are involved in transport of hydrophobic compounds and as such function in defence of the body from toxic natural products in the diet. P-glycoproteins are also a critical component of the mammalian blood-brain barrier and their function is necessary for tolerance of drugs that are normally minimally toxic to mammals, such as ivermectin. Strains of worm carrying Pgp mutants have demonstrated enhanced sensitivity to natural pathogens of C. elegans such as Pseudomonas aeruginosa (Mahajan-Miklos et al., (1998) Cell 96:47-56). We estimate that there are more than 60 ABC transporters in the Caenorhabditis elegans genome. The functions of most of these are unknown. We have completed a phylogenetic analysis of all these ABC transporter genes and we find that the P-glycoprotein subclass in C. elegans contains 15 genes. Previously only 4 Pgps had been named in C. elegans , and only two of these have been knocked out (Broeks et al., (1995) EMBO J. 14:1858-66). Production of knockout mutations in all 15 genes is in progress through the auspices of the international C. elegans gene knockout consortium. We are screening the P-glycoprotein knockout worms for potential drug sensitivity phenotypes using an assay which monitors the uptake and distribution of fluorescent drugs. Results so far indicate that the pgp-1 knockout, previously described as lacking a phenotype, does alter the distribution of the fluorescent drug rhodamine 123 within the body of the worm, and is thus a candidate drug resistance gene also. This approach, when extended to all ABC transporters, is expected to ultimately identify all such genes involved in the resistance of C. elegans to environmental insult.

J Hodgkin (1999) International C. elegans Meeting "A new bacterial pathogen of C.elegans, and the isolation of resistant mutants"

J Hodgkin

[International C. elegans Meeting, 1999]

Two spontaneous variant strains of C. elegans , originally isolated on the basis of a Dar (Deformed Anal Region) phenotype, have been found to suffer from a disease rather than a genetic alteration. They are infected by slow-growing gram-positive bacteria, which belong to a species of the large coryneform genus Aureobacterium/Microbacterium . The bacteria adhere to the surface of the rectum and post-anal region of worms, causing a striking localized swelling of the underlying hypodermal tissues. The bacteria do not appear to invade across the cuticle. The swelling leads to interference with defecation, and hence to constipation and slower growth rate in infected worms, but the infection does not usually kill them. Response by the worm has been investigated first by surveying a variety of known mutants for alteration in the infection, either to resistance or to hypersensitivity. Mutants known to be altered in susceptibility to killing by virulent Pseudomonas aeruginosa (Mahajan-Miklos et al., 1999, Cell 96: 47-56) still develop a standard Dar phenotype on infection. Mutations affecting possible components of the Toll pathway were also tested (see abstract by Link et al.), with negative results. Mutants representing about 200 other genes have been tested, and most were found to exhibit a standard Dar response. Mutations in three of eight tested srf genes (affecting surface antigenicity) lead to resistance, with no tail swelling and no reduction in growth rate. The slow growth caused by the bacteria permits an efficient selection for mutants that are resistant to infection. These turn out to be relatively frequent. Of the first 30 resistant mutants to be analysed, a few proved to be new isolates of srf-2, srf-3 or srf-5 , but most define new genetic loci, termed bus (for Bacterially Un-Swollen). So far, at least eight distinct bus genes have been defined and genetically mapped. Some probably mediate resistance by altering bacterial adherence to the cuticle, but others may affect different steps in the progress of infection and induced swelling. The processes of infection and resistance provide promising opportunities for the investigation of several areas of C. elegans biology, such as response to infection, host-parasite interaction, cuticle structure and hypodermal morphogenesis.