Sternberg PW

References (9)

Title : Combinatorial Assembly of Modular Glucosides via Carboxylesterases Regulates C. elegans Starvation Survival - Wrobel_2021_J.Am.Chem.Soc__
Author(s) : Wrobel CJJ , Yu J , Rodrigues PR , Ludewig AH , Curtis BJ , Cohen SM , Fox BW , O'Donnell MP , Sternberg PW , Schroeder FC
Ref : Journal of the American Chemical Society , : , 2021
Abstract : The recently discovered modular glucosides (MOGLs) form a large metabolite library derived from combinatorial assembly of moieties from amino acid, neurotransmitter, and lipid metabolism in the model organism C. elegans. Combining CRISPR-Cas9 genome editing, comparative metabolomics, and synthesis, we show that the carboxylesterase homologue Cel-CEST-1.2 is responsible for specific 2-O-acylation of diverse glucose scaffolds with a wide variety of building blocks, resulting in more than 150 different MOGLs. We further show that this biosynthetic role is conserved for the closest homologue of Cel-CEST-1.2 in the related nematode species C. briggsae, Cbr-CEST-2. Expression of Cel-cest-1.2 and MOGL biosynthesis are strongly induced by starvation conditions in C. elegans, one of the premier model systems for mechanisms connecting nutrition and physiology. Cel-cest-1.2-deletion results in early death of adult animals under starvation conditions, providing first insights into the biological functions of MOGLs.
ESTHER : Wrobel_2021_J.Am.Chem.Soc__
PubMedSearch : Wrobel_2021_J.Am.Chem.Soc__
PubMedID: 34460264
Gene_locus related to this paper: caebr-a8wyd4 , caeel-t02b5.1 , caeel-t02b5.3

Title : Modular metabolite assembly in C. elegans depends on carboxylesterases and formation of lysosome-related organelles - Le_2020_Elife_9_
Author(s) : Le HH , Wrobel CJ , Cohen SM , Yu J , Park H , Helf MJ , Curtis BJ , Kruempel JC , Rodrigues PR , Hu PJ , Sternberg PW , Schroeder FC
Ref : Elife , 9 : , 2020
Abstract : Signaling molecules derived from attachment of diverse metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that a pathway mediating formation of intestinal lysosome-related organelles (LROs) is required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Similar to modular ascarosides, the modular glucosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism, suggesting that modular glucosides, like the ascarosides, may serve signaling functions. We further show that carboxylesterases that localize to intestinal organelles are required for the assembly of both modular ascarosides and glucosides via ester and amide linkages. Further exploration of LRO function and carboxylesterase homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms.
ESTHER : Le_2020_Elife_9_
PubMedSearch : Le_2020_Elife_9_
PubMedID: 33063667

Title : The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families - Schwarz_2015_Nat.Genet_47_416
Author(s) : Schwarz EM , Hu Y , Antoshechkin I , Miller MM , Sternberg PW , Aroian RV
Ref : Nat Genet , 47 :416 , 2015
Abstract : Hookworms infect over 400 million people, stunting and impoverishing them. Sequencing hookworm genomes and finding which genes they express during infection should help in devising new drugs or vaccines against hookworms. Unlike other hookworms, Ancylostoma ceylanicum infects both humans and other mammals, providing a laboratory model for hookworm disease. We determined an A. ceylanicum genome sequence of 313 Mb, with transcriptomic data throughout infection showing expression of 30,738 genes. Approximately 900 genes were upregulated during early infection in vivo, including ASPRs, a cryptic subfamily of activation-associated secreted proteins (ASPs). Genes downregulated during early infection included ion channels and G protein-coupled receptors; this downregulation was observed in both parasitic and free-living nematodes. Later, at the onset of heavy blood feeding, C-lectin genes were upregulated along with genes for secreted clade V proteins (SCVPs), encoding a previously undescribed protein family. These findings provide new drug and vaccine targets and should help elucidate hookworm pathogenesis.
ESTHER : Schwarz_2015_Nat.Genet_47_416
PubMedSearch : Schwarz_2015_Nat.Genet_47_416
PubMedID: 25730766
Gene_locus related to this paper: 9bila-a0a016wyk0 , 9bila-a0a016u0c0 , 9bila-a0a016u0y8

Title : Comparative genomics of Steinernema reveals deeply conserved gene regulatory networks - Dillman_2015_Genome.Biol_16_200
Author(s) : Dillman AR , Macchietto M , Porter CF , Rogers A , Williams B , Antoshechkin I , Lee MM , Goodwin Z , Lu X , Lewis EE , Goodrich-Blair H , Stock SP , Adams BJ , Sternberg PW , Mortazavi A
Ref : Genome Biol , 16 :200 , 2015
Abstract : BACKGROUND: Parasitism is a major ecological niche for a variety of nematodes. Multiple nematode lineages have specialized as pathogens, including deadly parasites of insects that are used in biological control. We have sequenced and analyzed the draft genomes and transcriptomes of the entomopathogenic nematode Steinernema carpocapsae and four congeners (S. scapterisci, S. monticolum, S. feltiae, and S. glaseri).
RESULTS: We used these genomes to establish phylogenetic relationships, explore gene conservation across species, and identify genes uniquely expanded in insect parasites. Protein domain analysis in Steinernema revealed a striking expansion of numerous putative parasitism genes, including certain protease and protease inhibitor families, as well as fatty acid- and retinol-binding proteins. Stage-specific gene expression of some of these expanded families further supports the notion that they are involved in insect parasitism by Steinernema. We show that sets of novel conserved non-coding regulatory motifs are associated with orthologous genes in Steinernema and Caenorhabditis.
CONCLUSIONS: We have identified a set of expanded gene families that are likely to be involved in parasitism. We have also identified a set of non-coding motifs associated with groups of orthologous genes in Steinernema and Caenorhabditis involved in neurogenesis and embryonic development that are likely part of conserved protein-DNA relationships shared between these two genera.
ESTHER : Dillman_2015_Genome.Biol_16_200
PubMedSearch : Dillman_2015_Genome.Biol_16_200
PubMedID: 26392177
Gene_locus related to this paper: 9bila-a0a1i7y7c9 , 9bila-a0a1i8a8u4 , 9bila-a0a1i7yci6 , 9bila-a0a1i7ys27 , 9bila-a0a1i7y373

Title : Genome and transcriptome of the porcine whipworm Trichuris suis - Jex_2014_Nat.Genet_46_701
Author(s) : Jex AR , Nejsum P , Schwarz EM , Hu L , Young ND , Hall RS , Korhonen PK , Liao S , Thamsborg S , Xia J , Xu P , Wang S , Scheerlinck JP , Hofmann A , Sternberg PW , Wang J , Gasser RB
Ref : Nat Genet , 46 :701 , 2014
Abstract : Trichuris (whipworm) infects 1 billion people worldwide and causes a disease (trichuriasis) that results in major socioeconomic losses in both humans and pigs. Trichuriasis relates to an inflammation of the large intestine manifested in bloody diarrhea, and chronic disease can cause malnourishment and stunting in children. Paradoxically, Trichuris of pigs has shown substantial promise as a treatment for human autoimmune disorders, including inflammatory bowel disease (IBD) and multiple sclerosis. Here we report whole-genome sequencing at approximately 140-fold coverage of adult male and female T. suis and approximately 80-Mb draft assemblies. We explore stage-, sex- and tissue-specific transcription of mRNAs and small noncoding RNAs.
ESTHER : Jex_2014_Nat.Genet_46_701
PubMedSearch : Jex_2014_Nat.Genet_46_701
PubMedID: 24929829
Gene_locus related to this paper: 9bila-a0a085nui3 , 9bila-a0a085mx66 , 9bila-a0a085lsb8 , 9bila-a0a085mja7 , 9bila-a0a085ly55 , 9bila-a0a085nlc5 , 9bila-a0a085nb82 , 9bila-a0a085n057 , 9bila-a0a085mjs6

Title : Genome of the human hookworm Necator americanus - Tang_2014_Nat.Genet_46_261
Author(s) : Tang YT , Gao X , Rosa BA , Abubucker S , Hallsworth-Pepin K , Martin J , Tyagi R , Heizer E , Zhang X , Bhonagiri-Palsikar V , Minx P , Warren WC , Wang Q , Zhan B , Hotez PJ , Sternberg PW , Dougall A , Gaze ST , Mulvenna J , Sotillo J , Ranganathan S , Rabelo EM , Wilson RK , Felgner PL , Bethony J , Hawdon JM , Gasser RB , Loukas A , Mitreva M
Ref : Nat Genet , 46 :261 , 2014
Abstract : The hookworm Necator americanus is the predominant soil-transmitted human parasite. Adult worms feed on blood in the small intestine, causing iron-deficiency anemia, malnutrition, growth and development stunting in children, and severe morbidity and mortality during pregnancy in women. We report sequencing and assembly of the N. americanus genome (244 Mb, 19,151 genes). Characterization of this first hookworm genome sequence identified genes orchestrating the hookworm's invasion of the human host, genes involved in blood feeding and development, and genes encoding proteins that represent new potential drug targets against hookworms. N. americanus has undergone a considerable and unique expansion of immunomodulator proteins, some of which we highlight as potential treatments against inflammatory diseases. We also used a protein microarray to demonstrate a postgenomic application of the hookworm genome sequence. This genome provides an invaluable resource to boost ongoing efforts toward fundamental and applied postgenomic research, including the development of new methods to control hookworm and human immunological diseases.
ESTHER : Tang_2014_Nat.Genet_46_261
PubMedSearch : Tang_2014_Nat.Genet_46_261
PubMedID: 24441737
Gene_locus related to this paper: necam-w2tsu7

Title : A lover and a fighter: the genome sequence of an entomopathogenic nematode Heterorhabditis bacteriophora - Bai_2013_PLoS.One_8_e69618
Author(s) : Bai X , Adams BJ , Ciche TA , Clifton S , Gaugler R , Kim KS , Spieth J , Sternberg PW , Wilson RK , Grewal PS
Ref : PLoS ONE , 8 :e69618 , 2013
Abstract : Heterorhabditis bacteriophora are entomopathogenic nematodes that have evolved a mutualism with Photorhabdus luminescens bacteria to function as highly virulent insect pathogens. The nematode provides a safe harbor for intestinal symbionts in soil and delivers the symbiotic bacteria into the insect blood. The symbiont provides virulence and toxins, metabolites essential for nematode reproduction, and antibiotic preservation of the insect cadaver. Approximately half of the 21,250 putative protein coding genes identified in the 77 Mbp high quality draft H. bacteriophora genome sequence were novel proteins of unknown function lacking homologs in Caenorhabditis elegans or any other sequenced organisms. Similarly, 317 of the 603 predicted secreted proteins are novel with unknown function in addition to 19 putative peptidases, 9 peptidase inhibitors and 7 C-type lectins that may function in interactions with insect hosts or bacterial symbionts. The 134 proteins contained mariner transposase domains, of which there are none in C. elegans, suggesting an invasion and expansion of mariner transposons in H. bacteriophora. Fewer Kyoto Encyclopedia of Genes and Genomes Orthologies in almost all metabolic categories were detected in the genome compared with 9 other sequenced nematode genomes, which may reflect dependence on the symbiont or insect host for these functions. The H. bacteriophora genome sequence will greatly facilitate genetics, genomics and evolutionary studies to gain fundamental knowledge of nematode parasitism and mutualism. It also elevates the utility of H. bacteriophora as a bridge species between vertebrate parasitic nematodes and the C. elegans model.
ESTHER : Bai_2013_PLoS.One_8_e69618
PubMedSearch : Bai_2013_PLoS.One_8_e69618
PubMedID: 23874975
Gene_locus related to this paper: hetba-a0a1i7xln9

Title : Multigenome DNA sequence conservation identifies Hox cis-regulatory elements - Kuntz_2008_Genome.Res_18_1955
Author(s) : Kuntz SG , Schwarz EM , DeModena JA , De Buysscher T , Trout D , Shizuya H , Sternberg PW , Wold BJ
Ref : Genome Res , 18 :1955 , 2008
Abstract : To learn how well ungapped sequence comparisons of multiple species can predict cis-regulatory elements in Caenorhabditis elegans, we made such predictions across the large, complex ceh-13/lin-39 locus and tested them transgenically. We also examined how prediction quality varied with different genomes and parameters in our comparisons. Specifically, we sequenced approximately 0.5% of the C. brenneri and C. sp. 3 PS1010 genomes, and compared five Caenorhabditis genomes (C. elegans, C. briggsae, C. brenneri, C. remanei, and C. sp. 3 PS1010) to find regulatory elements in 22.8 kb of noncoding sequence from the ceh-13/lin-39 Hox subcluster. We developed the MUSSA program to find ungapped DNA sequences with N-way transitive conservation, applied it to the ceh-13/lin-39 locus, and transgenically assayed 21 regions with both high and low degrees of conservation. This identified 10 functional regulatory elements whose activities matched known ceh-13/lin-39 expression, with 100% specificity and a 77% recovery rate. One element was so well conserved that a similar mouse Hox cluster sequence recapitulated the native nematode expression pattern when tested in worms. Our findings suggest that ungapped sequence comparisons can predict regulatory elements genome-wide.
ESTHER : Kuntz_2008_Genome.Res_18_1955
PubMedSearch : Kuntz_2008_Genome.Res_18_1955
PubMedID: 18981268
Gene_locus related to this paper: 9pelo-b6vbi9 , 9pelo-b6vbj0 , 9pelo-b6vbj1 , 9pelo-b6vbj2

Title : Goalpha regulates volatile anesthetic action in Caenorhabditis elegans - van Swinderen_2001_Genetics_158_643
Author(s) : van Swinderen B , Metz LB , Shebester LD , Mendel JE , Sternberg PW , Crowder CM
Ref : Genetics , 158 :643 , 2001
Abstract : To identify genes controlling volatile anesthetic (VA) action, we have screened through existing Caenorhabditis elegans mutants and found that strains with a reduction in Go signaling are VA resistant. Loss-of-function mutants of the gene goa-1, which codes for the alpha-subunit of Go, have EC(50)s for the VA isoflurane of 1.7- to 2.4-fold that of wild type. Strains overexpressing egl-10, which codes for an RGS protein negatively regulating goa-1, are also isoflurane resistant. However, sensitivity to halothane, a structurally distinct VA, is differentially affected by Go pathway mutants. The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities. Double mutant strains carrying mutations in both goa-1 and unc-64, which codes for a neuronal syntaxin previously found to regulate VA sensitivity, show that the syntaxin mutant phenotypes depend in part on goa-1 expression. Pharmacological assays using the cholinesterase inhibitor aldicarb suggest that VAs and GOA-1 similarly downregulate cholinergic neurotransmitter release in C. elegans. Thus, the mechanism of action of VAs in C. elegans is regulated by Goalpha, and presynaptic Goalpha-effectors are candidate VA molecular targets.
ESTHER : van Swinderen_2001_Genetics_158_643
PubMedSearch : van Swinderen_2001_Genetics_158_643
PubMedID: 11404329