Project description:Blood flukes of the genus Schistosoma (Platyhelminthes, Trematoda, Digenea) are responsible for the chronic debilitating disease schistosomiasis / bilharzia, widely considered to be second only to malaria as a global health problem and an incalculable drain on the economic development of endemic countries. Since 1994, the World Health Organization has supported a genome initiative for Schistosoma, the Schistosoma Genome Network, aimed at identifying new targets for drug and vaccine development, understanding the molecular basis of parasite metabolism and development and determining biological variation. The study of small-RNAs as key players in the regulation of gene expression differentiation is important to the understanding of the parasites biology. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:The schistosome homolog of ftz-f1 is a nuclear receptor. In order to understand the function of Smftz-f1, we performed RNAseq with samples taken on two days, Day 5 and Day 9, on either control (RNAi) or Smftz-f1 (RNAi) parasites to see the transcriptional consequences of Smftz-f1 RNAi and to find potential transcriptional targets.
Project description:The schistosome homolog of hnf4 is involved in parasite blood feeding and stem cell biology. In order to understand the function of hnf4, we performed RNAseq on either control(RNAi) or hnf4(RNAi) parasites to see the transcriptional consequences of hnf4 RNAi
Project description:A kinetic model of S. mansoni glycolysis in which we can vary the allosteric regulation on lactate dehydrogenase (LDH). Because not enough kinetic data are available for all the schistosome enzymes to construct a complete schistosome glycolysis model de novo, we here adjusted the well-established glycolysis model of the eukaryotic microbe Saccharomyces cerevisiae (Teusink et al., 2000; van Eunen et al., 2012; van Heerden et al., 2014). We removed reactions from the yeast model that are not used in schistosomes and added glycogen metabolism, a Krebs cycle, respiration and an allosterically regulated LDH that was parameterized on multiple in vitro kinetic data sets for schistosome LDH. Additional files are published on Zenodo: https://zenodo.org/records/10401097
Project description:Schistosoma mansoni is a flatworm that causes schistosomiasis, a neglected tropical disease that affects over 200 million people worldwide. New therapeutic targets are needed with only one drug available for treatment and no vaccine. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential. In other organisms, they have been shown as involved with reproduction, stem cell maintenance and drug resistance, and they tend to exhibit tissue-specific expression patterns. S. mansoni expresses thousands of lncRNA genes; however, the cell type expression patterns of lncRNAs in the parasite remain uncharacterized. Here, we have re-analyzed public single-cell RNA-sequencing (scRNA-seq) data obtained from adult S. mansoni to identify the lncRNAs signature of adult schistosome cell types. A total of 8023 lncRNAs (79% of all lncRNAs) was detected. Analyses of the lncRNAs expression profiles in the cells using statistically stringent criteria were performed to identify 74 lncRNA gene markers of cell clusters. Male gamete and tegument lineage clusters contained most of the cluster-specific lncRNA markers. We also identified lncRNA markers of specific neural clusters. Whole-mount in situ hybridization (WISH) and double fluorescence in situ hybridization were used to validate the cluster-specific expression of 13 out of 16 lncRNA gene markers (81%) in the male and female adult parasite tissues; for one of these 16 gene loci, probes for two different lncRNA isoforms were used, which showed differential isoforms usage in testis and ovary. An atlas of the expression profiles across the cell clusters of all lncRNAs detected in our analysis is available as a public website resource. The results presented here give strong support to a tissue-specific expression and to a regulated expression program of lncRNAs in S. mansoni. This will be the basis for further exploration of lncRNA genes as potential therapeutic targets.
Project description:Schistosomiasis is a disease caused by parasitic worms that significantly impacts on the lives of approximately 250 million people. During infection, female parasites release thousands of eggs, a significant number of which become trapped in the liver. The entrapment of the eggs triggers immune and inflammatory responses that in turn cause many of the health problems associated with the disease. In this study we analyzed the gene expression profiles of livers from mice infected with the human parasite Schistosoma mansoni over multiple time points, beginning when the parasites start to lay eggs. Mice were treated with a lethal dose of the anti-schistosomal drug praziquantel, and we identified a number of different genes and pathways that are central to immune and inflammatory responses that are active even in the absence of egg deposition. Praziquantel is the only drug available to treat schistosomiasis, however it is ineffective against juvenile parasites during the early stages of mammalian infection. We also show that the development of drug resistance may be due to the improved efficacy of the juvenile parasite to actively excrete the drug. These results provide insights into the effect of praziquantel on the host response to infection as well as ability of juvenile parasites to overcome the lethal effect of the drug.
Project description:Schistosomes are blood-dwelling helminth parasites causing a debilitating disease in the tropics. Major challenges to control persist and vaccines would provide an additional tool, but their development has been problematic. During the self-cure response of Rhesus macaques, antibodies target proteins from the tegument, gut and esophagus, the last of which is the least investigated. We developed a dissection technique that permitted comparative proteomics on the schistosome esophagus and gut. A shotgun analysis applied to male heads identified 13 MEG proteins, eleven of which were uniquely located in the esophageal glands. Antigenic variation by alternative splicing of MEG proteoforms was confirmed together with a specialised machinery for protein glycosylation in the esophagus. Moreover some gastrodermal secretions were highly enriched in the gut, while others were more uniformly distributed, potentially as markers of lysosomal activity. Collectively, our findings provide a more rational, better-oriented selection of schistosome vaccine candidates in the context of a proven model of protective immunity.