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152. Phylogenomic and biogeographic reconstruction of the Trichinella complex

Author

Korhonen, Pasi K., primary, Pozio, Edoardo, additional, La Rosa, Giuseppe, additional, Chang, Bill C. H., additional, Koehler, Anson V., additional, Hoberg, Eric P., additional, Boag, Peter R., additional, Tan, Patrick, additional, Jex, Aaron R., additional, Hofmann, Andreas, additional, Sternberg, Paul W., additional, Young, Neil D., additional, and Gasser, Robin B., additional

Published
2016
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154. Time-Dependent Transcriptional Changes in Axenic Giardia duodenalis Trophozoites

Author

Ansell, Brendan R. E., McConville, Malcolm J., Baker, Louise, Korhonen, Pasi K., Young, Neil D., Hall, Ross S., Rojas, Cristian A. A., Svärd, Staffan G., Gasser, Robin B., Jex, Aaron R., Ansell, Brendan R. E., McConville, Malcolm J., Baker, Louise, Korhonen, Pasi K., Young, Neil D., Hall, Ross S., Rojas, Cristian A. A., Svärd, Staffan G., Gasser, Robin B., and Jex, Aaron R.

Abstract

Giardia duodenalis is the most common gastrointestinal protozoan parasite of humans and a significant contributor to the global burden of both diarrheal disease and post-infectious chronic disorders. Although G. duodenalis can be cultured axenically, significant gaps exist in our understanding of the molecular biology and metabolism of this pathogen. The present study employed RNA sequencing to characterize the mRNA transcriptome of G. duodenalis trophozoites in axenic culture, at log (48 h of growth), stationary (60 h), and declining (96 h) growth phases. Using similar to 400-times coverage of the transcriptome, we identified 754 differentially transcribed genes (DTGs), mainly representing two large DTG groups: 438 that were down-regulated in the declining phase relative to log and stationary phases, and 281 that were up-regulated. Differential transcription of prominent antioxidant and glycolytic enzymes implicated oxygen tension as a key factor influencing the transcriptional program of axenic trophozoites. Systematic bioinformatic characterization of numerous DTGs encoding hypothetical proteins of unknown function was achieved using structural homology searching. This powerful approach greatly informed the differential transcription analysis and revealed putative novel antioxidant-coding genes, and the presence of a nearcomplete two-component-like signaling system that may link cytosolic redox or metabolite sensing to the observed transcriptional changes. Motif searching applied to promoter regions of the two large DTG groups identified different putative transcription factor-binding motifs that may underpin global transcriptional regulation. This study provides new insights into the drivers and potential mediators of transcriptional variation in axenic G. duodenalis and provides context for static transcriptional studies.

Published
2015
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155. Genetic blueprint of the zoonotic pathogen Toxocara canis

Author

Zhu, Xing-Quan, Korhonen, Pasi K., Cai, Huimin, Young, Neil D., Nejsum, Peter, von Samson-Himmelstjerna, Georg, Boag, Peter R., Tan, Patrick, Li, Qiye, Min, Jiumeng, Yang, Yulan, Wang, Xiuhua, Fang, Xiaodong, Hall, Ross S., Hofmann, Andreas, Sternberg, Paul W., Jex, Aaron R., Gasser, Robin B., Zhu, Xing-Quan, Korhonen, Pasi K., Cai, Huimin, Young, Neil D., Nejsum, Peter, von Samson-Himmelstjerna, Georg, Boag, Peter R., Tan, Patrick, Li, Qiye, Min, Jiumeng, Yang, Yulan, Wang, Xiuhua, Fang, Xiaodong, Hall, Ross S., Hofmann, Andreas, Sternberg, Paul W., Jex, Aaron R., and Gasser, Robin B.

Abstract

Toxocara canis is a zoonotic parasite of major socioeconomic importance worldwide. In humans, this nematode causes disease (toxocariasis) mainly in the under-privileged communities in developed and developing countries. Although relatively well studied from clinical and epidemiological perspectives, to date, there has been no global investigation of the molecular biology of this parasite. Here we use next-generation sequencing to produce a draft genome and transcriptome of T. canis to support future biological and biotechnological investigations. This genome is 317 Mb in size, has a repeat content of 13.5% and encodes at least 18,596 protein-coding genes. We study transcription in a larval, as well as adult female and male stages, characterize the parasite's gene-silencing machinery, explore molecules involved in development or host-parasite interactions and predict intervention targets. The draft genome of T. canis should provide a useful resource for future molecular studies of this and other, related parasites.

Published
2015

158. Exploring molecular variation in Schistosoma japonicum in China

Author

Young, Neil D., primary, Chan, Kok-Gan, additional, Korhonen, Pasi K., additional, Min Chong, Teik, additional, Ee, Robson, additional, Mohandas, Namitha, additional, Koehler, Anson V., additional, Lim, Yan-Lue, additional, Hofmann, Andreas, additional, Jex, Aaron R., additional, Qian, Baozhen, additional, Chilton, Neil B., additional, Gobert, Geoffrey N., additional, McManus, Donald P., additional, Tan, Patrick, additional, Webster, Bonnie L., additional, Rollinson, David, additional, and Gasser, Robin B., additional

Published
2015
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160. (\it SOX9\) duplication linked to intersex in deer

Author

Kropatsch, Regina (Dr.), Dekomien, Gabriele (Dr. rer. nat.), Akkad, Denis A. (Dr.), Gerding, Wanda Maria (Dr.), Petrasch-Parwez, Elisabeth (Dr. med.), Young, Neil D. (Dr.), Altmüller, Janine (Dr. med.), Nürnberg, Peter (Prof. Dr. rer. nat.), Gasser, Robin B. (Prof.), and Epplen, Jörg T. (Prof. Dr. med.)

Abstract

A complex network of genes determines sex in mammals. Here, we studied a European roe deer with an intersex phenotype that was consistent with a XY genotype with incomplete male-determination. Whole genome sequencing and quantitative real-time PCR analyses revealed a triple dose of the \(\it SOX9\) gene, allowing insights into a new genetic defect in a wild animal.

Published
2013

162. Lucilia cuprina genome unlocks parasitic fly biology to underpin future interventions

Author

Anstead, Clare A., primary, Korhonen, Pasi K., additional, Young, Neil D., additional, Hall, Ross S., additional, Jex, Aaron R., additional, Murali, Shwetha C., additional, Hughes, Daniel S.T., additional, Lee, Siu F., additional, Perry, Trent, additional, Stroehlein, Andreas J., additional, Ansell, Brendan R.E., additional, Breugelmans, Bert, additional, Hofmann, Andreas, additional, Qu, Jiaxin, additional, Dugan, Shannon, additional, Lee, Sandra L., additional, Chao, Hsu, additional, Dinh, Huyen, additional, Han, Yi, additional, Doddapaneni, Harsha V., additional, Worley, Kim C., additional, Muzny, Donna M., additional, Ioannidis, Panagiotis, additional, Waterhouse, Robert M., additional, Zdobnov, Evgeny M., additional, James, Peter J., additional, Bagnall, Neil H., additional, Kotze, Andrew C., additional, Gibbs, Richard A., additional, Richards, Stephen, additional, Batterham, Philip, additional, and Gasser, Robin B., additional

Published
2015
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164. Of Monkeys and Men: Immunomic Profiling of Sera from Humans and Non-Human Primates Resistant to Schistosomiasis Reveals Novel Potential Vaccine Candidates

Author

Pearson, Mark S., primary, Becker, Luke, additional, Driguez, Patrick, additional, Young, Neil D., additional, Gaze, Soraya, additional, Mendes, Tiago, additional, Li, Xiao-Hong, additional, Doolan, Denise L., additional, Midzi, Nicholas, additional, Mduluza, Takafira, additional, McManus, Donald P., additional, Wilson, R. Alan, additional, Bethony, Jeffrey M., additional, Nausch, Norman, additional, Mutapi, Francisca, additional, Felgner, Philip L., additional, and Loukas, Alex, additional

Published
2015
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166. Genetic blueprint of the zoonotic pathogen Toxocara canis

Author

Zhu, Xing-Quan, primary, Korhonen, Pasi K., additional, Cai, Huimin, additional, Young, Neil D., additional, Nejsum, Peter, additional, von Samson-Himmelstjerna, Georg, additional, Boag, Peter R., additional, Tan, Patrick, additional, Li, Qiye, additional, Min, Jiumeng, additional, Yang, Yulan, additional, Wang, Xiuhua, additional, Fang, Xiaodong, additional, Hall, Ross S., additional, Hofmann, Andreas, additional, Sternberg, Paul W., additional, Jex, Aaron R., additional, and Gasser, Robin B., additional

Published
2015
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167. Massively Parallel Sequencing and Analysis of the Necatoramericanus Transcriptome

Author

Cantacessi, Cinzia, Mitreva, Makedonka, Jex, Aaron R., Young, Neil D., Campbell, Bronwyn E., Hall, Ross S., Doyle, Maria A., Rabelo, Elida M., Ranganathan, Shoba, Sternberg, Paul W., Loukas, Alex, and Gasser, Robin B.

Subjects
Other medical sciences, parasitic diseases
Abstract

Background: The blood-feeding hookworm Necator americanus infects hundreds of millions of people worldwide. In order to elucidate fundamental molecular biological aspects of this hookworm, the transcriptome of the adult stage of Necator americanus was explored using next-generation sequencing and bioinformatic analyses. Methodology/PrincipalFindings:A total of 19,997 contigs were assembled from the sequence data; 6,771 of these contigs had known orthologues in the free-living nematode Caenorhabditis elegans, and most of them encoded proteins with WD40 repeats (10.6%), proteinase inhibitors (7.8%) or calcium-binding EF-hand proteins (6.7%). Bioinformatic analyses inferred that the C. elegans homologues are involved mainly in biological pathways linked to ribosome biogenesis (70%), oxidative phosphorylation (63%) and/or proteases (60%); most of these molecules were predicted to be involved in more than one biological pathway. Comparative analyses of the transcriptomes of N. americanus and the canine hookworm, Ancylostoma caninum, revealed qualitative and quantitative differences. For instance, proteinase inhibitors were inferred to be highly represented in the former species, whereas SCP/Tpx-1/Ag5/PR-1/Sc7 proteins ( = SCP/TAPS or Ancylostoma-secreted proteins) were predominant in the latter. In N. americanus, essential molecules were predicted using a combination of orthology mapping and functional data available for C. elegans. Further analyses allowed the prioritization of 18 predicted drug targets which did not have homologues in the human host. These candidate targets were inferred to be linked to mitochondrial (e.g., processing proteins) or amino acid metabolism (e.g., asparagine t-RNA synthetase). Conclusions: This study has provided detailed insights into the transcriptome of the adult stage of N. americanus and examines similarities and differences between this species and A. caninum. Future efforts should focus on comparative transcriptomic and proteomic investigations of the other predominant human hookworm, A. duodenale, for both fundamental and applied purposes, including the prevalidation of anti-hookworm drug targets.

Published
2010

168. The Opisthorchis viverrini genome provides insights into life in the bile duct

Author

Young, Neil D., Nagarajan, Niranjan, Lin, Suling Joyce, Korhonen, Pasi K., Jex, Aaron R., Hall, Ross S., Safavi-Hemami, Helena, Kaewkong, Worasak, Bertrand, Denis, Gao, Song, Seet, Qihui, Wongkham, Sopit, Teh, Bin Tean, Wongkham, Chaisiri, Intapan, Pewpan Maleewong, Maleewong, Wanchai, Yang, Xinhua, Hu, Min, Wang, Zuo, Hofmann, Andreas, Sternberg, Paul W., Tan, Patrick, Wang, Jun, Gasser, Robin B., Young, Neil D., Nagarajan, Niranjan, Lin, Suling Joyce, Korhonen, Pasi K., Jex, Aaron R., Hall, Ross S., Safavi-Hemami, Helena, Kaewkong, Worasak, Bertrand, Denis, Gao, Song, Seet, Qihui, Wongkham, Sopit, Teh, Bin Tean, Wongkham, Chaisiri, Intapan, Pewpan Maleewong, Maleewong, Wanchai, Yang, Xinhua, Hu, Min, Wang, Zuo, Hofmann, Andreas, Sternberg, Paul W., Tan, Patrick, Wang, Jun, and Gasser, Robin B.

Published
2014

169. Genome and transcriptome of the porcine whipworm Trichuris suis

Author

Jex, Aaron R., Nejsum, Peter, Schwarz, Erich M., Hu, Li, Young, Neil D., Hall, Ross S., Korhonen, Pasi K., Liao, Shengguang, Thamsborg, Stig Milan, Xia, Jinquan, Xu, Pengwei, Wang, Shaowei, Scheerlinck, Jean-Pierre Y., Hofmann, Andreas, Sternberg, Paul W., Wang, Jun, Gasser, Robin B., Jex, Aaron R., Nejsum, Peter, Schwarz, Erich M., Hu, Li, Young, Neil D., Hall, Ross S., Korhonen, Pasi K., Liao, Shengguang, Thamsborg, Stig Milan, Xia, Jinquan, Xu, Pengwei, Wang, Shaowei, Scheerlinck, Jean-Pierre Y., Hofmann, Andreas, Sternberg, Paul W., Wang, Jun, and Gasser, Robin B.

Published
2014

170. Mitochondrial genomes of Trichinella species and genotypes – a basis for diagnosis, and systematic and epidemiological explorations

Author

Mohandas, Namitha, primary, Pozio, Edoardo, additional, La Rosa, Giuseppe, additional, Korhonen, Pasi K., additional, Young, Neil D., additional, Koehler, Anson V., additional, Hall, Ross S., additional, Sternberg, Paul W., additional, Boag, Peter R., additional, Jex, Aaron R., additional, Chang, Bill C.H., additional, and Gasser, Robin B., additional

Published
2014
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176. The Opisthorchis viverrini genome provides insights into life in the bile duct

Author

Young, Neil D., primary, Nagarajan, Niranjan, additional, Lin, Suling Joyce, additional, Korhonen, Pasi K., additional, Jex, Aaron R., additional, Hall, Ross S., additional, Safavi-Hemami, Helena, additional, Kaewkong, Worasak, additional, Bertrand, Denis, additional, Gao, Song, additional, Seet, Qihui, additional, Wongkham, Sopit, additional, Teh, Bin Tean, additional, Wongkham, Chaisiri, additional, Intapan, Pewpan Maleewong, additional, Maleewong, Wanchai, additional, Yang, Xinhua, additional, Hu, Min, additional, Wang, Zuo, additional, Hofmann, Andreas, additional, Sternberg, Paul W., additional, Tan, Patrick, additional, Wang, Jun, additional, and Gasser, Robin B., additional

Published
2014
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178. Combined Proteomic and Transcriptomic Interrogation of the Venom Gland of Conus geographus Uncovers Novel Components and Functional Compartmentalization

Author

Safavi-Hemami, Helena, primary, Hu, Hao, additional, Gorasia, Dhana G., additional, Bandyopadhyay, Pradip K., additional, Veith, Paul D., additional, Young, Neil D., additional, Reynolds, Eric C., additional, Yandell, Mark, additional, Olivera, Baldomero M., additional, and Purcell, Anthony W., additional

Published
2014
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180. Analysis of the transcriptome of adult Dictyocaulus filaria and comparison with Dictyocaulus viviparus, with a focus on molecules involved in host–parasite interactions

Author

Mangiola, Stefano, primary, Young, Neil D., additional, Sternberg, Paul W., additional, Strube, Christina, additional, Korhonen, Pasi K., additional, Mitreva, Makedonka, additional, Scheerlinck, Jean-Pierre, additional, Hofmann, Andreas, additional, Jex, Aaron R., additional, and Gasser, Robin B., additional

Published
2014
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182. SOX9 Duplication Linked to Intersex in Deer

Author

Kropatsch, Regina, Dekomien, Gabriele, Akkad, Denis A., Gerding, Wanda M., Petrasch-Parwez, Elisabeth, Young, Neil D., Altmueller, Janine, Nuernberg, Peter, Gasser, Robin B., Epplen, Joerg T., Kropatsch, Regina, Dekomien, Gabriele, Akkad, Denis A., Gerding, Wanda M., Petrasch-Parwez, Elisabeth, Young, Neil D., Altmueller, Janine, Nuernberg, Peter, Gasser, Robin B., and Epplen, Joerg T.

Abstract

A complex network of genes determines sex in mammals. Here, we studied a European roe deer with an intersex phenotype that was consistent with a XY genotype with incomplete male-determination. Whole genome sequencing and quantitative real-time PCR analyses revealed a triple dose of the SOX9 gene, allowing insights into a new genetic defect in a wild animal.

Published
2013

183. The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus.

Author

Schwarz, Erich M, Schwarz, Erich M, Korhonen, Pasi K, Campbell, Bronwyn E, Young, Neil D, Jex, Aaron R, Jabbar, Abdul, Hall, Ross S, Mondal, Alinda, Howe, Adina C, Pell, Jason, Hofmann, Andreas, Boag, Peter R, Zhu, Xing-Quan, Gregory, T, Loukas, Alex, Williams, Brian A, Antoshechkin, Igor, Brown, C, Sternberg, Paul W, Gasser, Robin B, Schwarz, Erich M, Schwarz, Erich M, Korhonen, Pasi K, Campbell, Bronwyn E, Young, Neil D, Jex, Aaron R, Jabbar, Abdul, Hall, Ross S, Mondal, Alinda, Howe, Adina C, Pell, Jason, Hofmann, Andreas, Boag, Peter R, Zhu, Xing-Quan, Gregory, T, Loukas, Alex, Williams, Brian A, Antoshechkin, Igor, Brown, C, Sternberg, Paul W, and Gasser, Robin B

Abstract

BackgroundThe barber's pole worm, Haemonchus contortus, is one of the most economically important parasites of small ruminants worldwide. Although this parasite can be controlled using anthelmintic drugs, resistance against most drugs in common use has become a widespread problem. We provide a draft of the genome and the transcriptomes of all key developmental stages of H. contortus to support biological and biotechnological research areas of this and related parasites.ResultsThe draft genome of H. contortus is 320 Mb in size and encodes 23,610 protein-coding genes. On a fundamental level, we elucidate transcriptional alterations taking place throughout the life cycle, characterize the parasite's gene silencing machinery, and explore molecules involved in development, reproduction, host-parasite interactions, immunity, and disease. The secretome of H. contortus is particularly rich in peptidases linked to blood-feeding activity and interactions with host tissues, and a diverse array of molecules is involved in complex immune responses. On an applied level, we predict drug targets and identify vaccine molecules.ConclusionsThe draft genome and developmental transcriptome of H. contortus provide a major resource to the scientific community for a wide range of genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological, and epidemiological investigations, and a solid foundation for biotechnological outcomes, including new anthelmintics, vaccines and diagnostic tests. This first draft genome of any strongylid nematode paves the way for a rapid acceleration in our understanding of a wide range of socioeconomically important parasites of one of the largest nematode orders.

Published
2013

184. Decoding the Ascaris suum genome using massively parallel sequencing and advanced bioinformatic methods:unprecedented prospects for fundamental and applied research

Author

Holland, Celia, Jex, Aaron R., Liu, Shiping, Li, Bo, Young, Neil D., Hall, Ross S., Li, Yingrui, Geldhof, Peter, Nejsum, Peter, Sternberg, Paul W., Wang, Jun, Yang, Huanming, Gasser, Robin B., Holland, Celia, Jex, Aaron R., Liu, Shiping, Li, Bo, Young, Neil D., Hall, Ross S., Li, Yingrui, Geldhof, Peter, Nejsum, Peter, Sternberg, Paul W., Wang, Jun, Yang, Huanming, and Gasser, Robin B.

Abstract

Parasitic nematodes cause substantial morbidity and mortality in animals and people globally and major losses to food production annually. Ascaris is among the commonest geohelminths of swine and people worldwide, and causes major disease and socioeconomic losses, particularly in developing countries. The control of ascariasis has become a global health and welfare priority, but current treatment programs carry a significant risk of inducing anthelmintic resistance. Therefore, there is a need to work toward the sustainable control of Ascaris/ascariasis, built on a solid understanding of its molecular biology and genetics. Recently, we reported the 273 megabase (Mb) draft genome of Ascaris suum (sequenced from the reproductive tract of a single adult female worm) and explored transcription in different organs, stages, and both sexes of this nematode using advanced sequencing and computer technologies. We characterized key genes and biological pathways linked to the parasite's migration in the host, and its immunobiology, reproduction, and development. We also predicted and prioritized drug targets in A. suum, providing a basis for discovering new groups of nematocides. The present chapter provides an account of these recent advances, describes new methodologies established, and emphasizes prospects for profound investigations into the comparative genomics, genetics, evolution, immunobiology, epidemiology, and ecology of Ascaris from both pig and human hosts as well as for the development of new interventions against ascariasis and other helminthiases. © 2013

Published
2013

185. Insights into the immuno-molecular biology of Angiostrongylus vasorum through transcriptomics—Prospects for new interventions

Author

Ansell, Brendan R.E., primary, Schnyder, Manuela, additional, Deplazes, Peter, additional, Korhonen, Pasi K., additional, Young, Neil D., additional, Hall, Ross S., additional, Mangiola, Stefano, additional, Boag, Peter R., additional, Hofmann, Andreas, additional, Sternberg, Paul W., additional, Jex, Aaron R., additional, and Gasser, Robin B., additional

Published
2013
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186. The transcriptome of Trichuris suis – first molecular insights into a parasite with curative properties for key immune diseases of humans

Author

Cantacessi , Cinzia, Young, Neil D., Nejsum, Peter, Jex, Aaron R., Campbell, Bronwyn E., Hall, Ross S., Thamsborg, Stig Milan, Scheerlinck, Jean-Pierre, Gasser, Robin B., Cantacessi , Cinzia, Young, Neil D., Nejsum, Peter, Jex, Aaron R., Campbell, Bronwyn E., Hall, Ross S., Thamsborg, Stig Milan, Scheerlinck, Jean-Pierre, and Gasser, Robin B.

Published
2011

187. SOX9 Duplication Linked to Intersex in Deer

Author

Kropatsch, Regina, primary, Dekomien, Gabriele, additional, Akkad, Denis A., additional, Gerding, Wanda M., additional, Petrasch-Parwez, Elisabeth, additional, Young, Neil D., additional, Altmüller, Janine, additional, Nürnberg, Peter, additional, Gasser, Robin B., additional, and Epplen, Jörg T., additional

Published
2013
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189. The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus

Author

Schwarz, Erich M, primary, Korhonen, Pasi K, additional, Campbell, Bronwyn E, additional, Young, Neil D, additional, Jex, Aaron R, additional, Jabbar, Abdul, additional, Hall, Ross S, additional, Mondal, Alinda, additional, Howe, Adina C, additional, Pell, Jason, additional, Hofmann, Andreas, additional, Boag, Peter R, additional, Zhu, Xing-Quan, additional, Gregory, T, additional, Loukas, Alex, additional, Williams, Brian A, additional, Antoshechkin, Igor, additional, Brown, C, additional, Sternberg, Paul W, additional, and Gasser, Robin B, additional

Published
2013
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190. Making sense of genomes of parasitic worms: Tackling bioinformatic challenges.

Author

Korhonen, Pasi K., Young, Neil D., and Gasser, Robin B.

Subjects
*HELMINTHS, *GENOMES, *BIOINFORMATICS, *BIOGEOGRAPHY, *PREDICTION models, *TARGETED drug delivery
Abstract

Billions of people and animals are infected with parasitic worms (helminths). Many of these worms cause diseases that have a major socioeconomic impact worldwide, and are challenging to control because existing treatment methods are often inadequate. There is, therefore, a need to work toward developing new intervention methods, built on a sound understanding of parasitic worms at molecular level, the relationships that they have with their animal hosts and/or the diseases that they cause. Decoding the genomes and transcriptomes of these parasites brings us a step closer to this goal. The key focus of this article is to critically review and discuss bioinformatic tools used for the assembly and annotation of these genomes and transcriptomes, as well as various post-genomic analyses of transcription profiles, biological pathways, synteny, phylogeny, biogeography and the prediction and prioritisation of drug target candidates. Bioinformatic pipelines implemented and established recently provide practical and efficient tools for the assembly and annotation of genomes of parasitic worms, and will be applicable to a wide range of other parasites and eukaryotic organisms. Future research will need to assess the utility of long-read sequence data sets for enhanced genomic assemblies, and develop improved algorithms for gene prediction and post-genomic analyses, to enable comprehensive systems biology explorations of parasitic organisms. [ABSTRACT FROM AUTHOR]

Published
2016
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191. MicroRNAs of Toxocara canis and their predicted functional roles.

Author

Guangxu Ma, Yongfang Luo, Honghong Zhu, Yongli Luo, Korhonen, Pasi K., Young, Neil D., Gasser, Robin B., and Rongqiong Zhou

Subjects
MICRORNA, VISCERAL larva migrans, TOXOCARIASIS, HOST-parasite relationships, TOXOCARA, SECERNENTEA, DRUG resistance, DIAGNOSIS
Abstract

Background: Toxocara canis is the causative agent of toxocariasis of humans and other animals. This parasitic nematode (roundworm) has a complex life cycle, in which substantial developmental changes and switches occur. As small non-coding RNAs (sRNAs) are key regulators of gene expression in a wide range of organisms, we explored these RNAs in T. canis to provide a basis for future studies of its developmental biology as well as host interactions and disease at the molecular level. Methods: We conducted high-throughput RNA sequencing and bioinformatic analyses to define sRNAs in individual male and female adults of T. canis. Results: Apart from snRNA and snoRNA, 560 and 619 microRNAs (miRNAs), including 5 and 2 novel miRNAs, were identified in male and female worms, respectively, without piRNAs being detected in either sex. An analysis of transcriptional profiles showed that, of 564 miRNAs predicted as being differentially transcribed between male and female individuals of T. canis, 218 miRNAs were transcribed exclusively in male and 277 in female worms. Functional enrichment analysis predicted that both male and female miRNAs were mainly involved in regulating embryonic morphogenesis, hemidesmosome assembly and genetic information processing. The miRNAs differentially transcribed between the sexes were predicted to be associated with sex determination, embryonic morphogenesis and nematode larval development. The roles of miRNAs were predicted based on gene ontology (GO) and KEGG pathway annotations. The miRNAs Tc-miR-2305 and Tc-miR-6090 are proposed to have roles in reproduction, embryo development and larval development, and Tc-let-7-5p, Tc-miR-34 and Tc-miR-100 appear to be involved in host-parasite interactions. Together with published information from previous studies, some miRNAs (such as Tc-miR-2861, Tc-miR-2881 and Tc-miR-5126) are predicted to represent drug targets and/or associated with drug resistance. Conclusions: This is the first exploration of miRNAs in T. canis, which could provide a basis for fundamental investigations of the developmental biology of the parasite, parasite-host interactions and toxocariasis as well as applied areas, such as the diagnosis of infection/disease, drug target discovery and drug resistance detection. [ABSTRACT FROM AUTHOR]

Published
2016
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192. The complement of family M1 aminopeptidases of Haemonchus contortus — Biotechnological implications.

Author

Mohandas, Namitha, Young, Neil D., Jabbar, Abdul, Korhonen, Pasi K., Koehler, Anson V., Hall, Ross S., Hu, Min, Hofmann, Andreas, and Gasser, Robin B.

Subjects
*AMINOPEPTIDASES, *HAEMONCHUS contortus, *BIOTECHNOLOGY, *RUMINANTS, *TRANSCRIPTION factors
Abstract

Although substantial research has been focused on the ‘hidden antigen’ H11 of Haemonchus contortus as a vaccine against haemonchosis in small ruminants, little is know about this and related aminopeptidases. In the present article, we reviewed genomic and transcriptomic data sets to define, for the first time, the complement of aminopeptidases (designated Hc- AP-1 to Hc- AP-13) of the family M1 with homologues in Caenorhabditis elegans , characterised by zinc-binding (HEXXH) and exo-peptidase (GAMEN) motifs. The three previously published H11 isoforms (accession nos. X94187 , FJ481146 and AJ249941 ) had most sequence similarity to Hc- AP-2 and Hc- AP-8, whereas unpublished isoforms (accession nos. AJ249942 and AJ311316 ) were both most similar to Hc- AP-3. The aminopeptidases characterised here had homologues in C. elegans . Hc- AP-1 to Hc- AP-8 were most similar in amino acid sequence (28–41%) to C. elegans T07F10.1; Hc- AP-9 and Hc- AP-10 to C. elegans PAM-1 (isoform b) (53–54% similar); Hc- AP-11 and Hc- AP-12 to C. elegans AC3.5 and Y67D8C.9 (26% and 50% similar, respectively); and Hc- AP-13 to C. elegans C42C1.11 and ZC416.6 (50–58% similar). Comparative analysis suggested that Hc- AP-1 to Hc- AP-8 play roles in digestion, metabolite excretion, neuropeptide processing and/or osmotic regulation, with Hc- AP-4 and Hc- AP-7 having male-specific functional roles. The analysis also indicated that Hc- AP-9 and Hc- AP-10 might be involved in the degradation of cyclin (B3) and required to complete meiosis. Hc- AP-11 represents a leucyl/cystinyl aminopeptidase, predicted to have metallopeptidase and zinc ion binding activity, whereas Hc- AP-12 likely encodes an aminopeptidase Q homologue also with these activities and a possible role in gonad function. Finally, Hc- AP-13 is predicted to encode an aminopeptidase AP-1 homologue of C. elegans with hydrolase activity, suggested to operate, possibly synergistically with a PEPT-1 ortholog, as an oligopeptide transporter in the gut for protein uptake and normal development and/or reproduction of the worm. An appraisal of structure-based amino acid sequence alignments revealed that all conceptually translated Hc -AP proteins, with the exception of Hc -AP-12, adopt a topology similar to those observed for the two subgroups of mammalian M1 aminopeptidases, which possess either three (I, II and IV) or four (I–IV) domains. In contrast, Hc -AP-12 lacks the N-terminal domain (I), but possesses a substantially expanded domain III. Although further work needs to be done to assess amino acid sequence conservation of the different aminopeptidases among individual worms within and among H. contortus populations, we hope that these insights will support future localisation, structural and functional studies of these molecules in H. contortus as well as facilitate future assessments of a recombinant subunit or cocktail vaccine against haemonchosis. [ABSTRACT FROM AUTHOR]

Published
2016
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193. The barber's pole worm CAP protein superfamily — A basis for fundamental discovery and biotechnology advances.

Author

Mohandas, Namitha, Young, Neil D., Jabbar, Abdul, Korhonen, Pasi K., Koehler, Anson V., Amani, Parisa, Hall, Ross S., Sternberg, Paul W., Jex, Aaron R., Hofmann, Andreas, and Gasser, Robin B.

Subjects
*HAEMONCHUS contortus, *IMMUNE response, *BIOTECHNOLOGY, *HELMINTHS, *CELLULAR signal transduction, *TRANSFORMING growth factors-beta
Abstract

Parasitic worm proteins that belong to the cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 (CAP) superfamily are proposed to play key roles in the infection process and the modulation of immune responses in host animals. However, there is limited information on these proteins for most socio-economically important worms. Here, we review the CAP protein superfamily of Haemonchus contortus (barber's pole worm), a highly significant parasitic roundworm (order Strongylida) of small ruminants. To do this, we mined genome and transcriptomic datasets, predicted and curated full-length amino acid sequences (n = 45), undertook systematic phylogenetic analyses of these data and investigated transcription throughout the life cycle of H. contortus . We inferred functions for selected Caenorhabditis elegans orthologs (including vap-1 , vap-2 , scl-5 and lon-1 ) based on genetic networking and by integrating data and published information, and were able to infer that a subset of orthologs and their interaction partners play pivotal roles in growth and development via the insulin-like and/or the TGF-beta signalling pathways. The identification of the important and conserved growth regulator LON-1 led us to appraise the three-dimensional structure of this CAP protein by comparative modelling. This model revealed the presence of different topological moieties on the canonical fold of the CAP domain, which coincide with an overall charge separation as indicated by the electrostatic surface potential map. These observations suggest the existence of separate sites for effector binding and receptor interactions, and thus support the proposal that these worm molecules act in similar ways as venoms act as ligands for chemokine receptors or G protein-coupled receptor effectors. In conclusion, this review should guide future molecular studies of these molecules, and could support the development of novel interventions against haemonchosis. [ABSTRACT FROM AUTHOR]

Published
2015
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195. SchistoDB: an updated genome resource for the three key schistosomes of humans

Author

Zerlotini, Adhemar, primary, Aguiar, Eric R. G. R., additional, Yu, Fudong, additional, Xu, Huayong, additional, Li, Yixue, additional, Young, Neil D., additional, Gasser, Robin B., additional, Protasio, Anna V., additional, Berriman, Matthew, additional, Roos, David S., additional, Kissinger, Jessica C., additional, and Oliveira, Guilherme, additional

Published
2012
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199. Whole-genome sequence of Schistosoma haematobium

Author

Young, Neil D, primary, Jex, Aaron R, additional, Li, Bo, additional, Liu, Shiping, additional, Yang, Linfeng, additional, Xiong, Zijun, additional, Li, Yingrui, additional, Cantacessi, Cinzia, additional, Hall, Ross S, additional, Xu, Xun, additional, Chen, Fangyuan, additional, Wu, Xuan, additional, Zerlotini, Adhemar, additional, Oliveira, Guilherme, additional, Hofmann, Andreas, additional, Zhang, Guojie, additional, Fang, Xiaodong, additional, Kang, Yi, additional, Campbell, Bronwyn E, additional, Loukas, Alex, additional, Ranganathan, Shoba, additional, Rollinson, David, additional, Rinaldi, Gabriel, additional, Brindley, Paul J, additional, Yang, Huanming, additional, Wang, Jun, additional, Wang, Jian, additional, and Gasser, Robin B, additional

Published
2012
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