Project description:Transcriptional profiling of TGF-beta treated Schistosoma mansoni adult worms vs. Non-treated Schistosoma mansoni adult worms Two conditions (treated vs. Non-treated) with three biological samples of treated worms (TGF1, 4 and 5) and two biological samples of non-treated worms that were pooled into a single sample (pool). For each sample (three treated or polled non-treated) were performed four technical replicas
Project description:HDACs inhibitors induces mortality in the parasite Schistosoma mansoni (schistosomula and adult worms), and became an interesting drug class for the development of new drugs to treat schistosomiasis. In order to understand the effect of histone hyperacetylation on the parasite, we tested the effect of the HDAC inhibitor Trichostatin A on schistosomula gene expression.
Project description:HDACs inhibitors induces mortality in the parasite Schistosoma mansoni (schistosomula and adult worms), and became an interesting drug class for the development of new drugs to treat schistosomiasis. In order to understand the effect of histone hyperacetylation on the parasite, we tested the effect of the HDAC inhibitor Trichostatin A on schistosomula gene expression.
Project description:HDACs inhibitors induces mortality in the parasite Schistosoma mansoni (schistosomula and adult worms), and became an interesting drug class for the development of new drugs to treat schistosomiasis. In order to understand the effect of histone hyperacetylation on the parasite, we tested the effect of the HDAC inhibitor Trichostatin A on schistosomula gene expression.
Project description:Transcriptional profiling using two subsequent developmental stages of Schistosoma mansoni (Egg vs. Miracidium; Cercaria vs. 7-days-old Schistosomulum; 7-days-old Schistosomulum vs. Adult worms
Project description:Transcriptional profiling using two subsequent developmental stages of Schistosoma mansoni (Egg vs. Miracidium; Cercaria vs. 7-days-old Schistosomulum; 7-days-old Schistosomulum vs. Adult worms Two conditions experiment; Developmental Stage 1 vs. Developmental Stage 2
Project description:Background: Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Therefore, there is a pressing need to explore the effects of PZQ on the parasites at the molecular level and to pursue alternative and/or or synergistic drugs against schistosomiasis. Methodology: We used a custom-designed Schistosoma mansoni oligo-microarray to explore the effects of a sublethal dose of praziquantel on S. mansoni adult worms’ gene expression. We used functional analysis of gene interaction networks to identify differentially expressed genes that are known targets of other drugs already tested in humans for diverse disease conditions. Omeprazole, a proton pump inhibitor drug that is widely prescribed, was tested in combination with praziquantel. We comparatively assessed the efficacy of praziquantel or omeprazole alone and in combination against S. mansoni adult worms in vitro over a period of 120 hours. Principal Findings: We identified sets of genes that were affected by praziquantel on both paired and unpaired females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired females), indicating that the transcriptomics changes induced by praziquantel are heavily influenced by the mating status. We also identified genes that were similarly affected by praziquantel in males and females. The use of sublethal doses of praziquantel together with omeprazole showed a significantly enhanced worm mortality in vitro compared to praziquantel alone, thus evidencing a synergic effect. Conclusions: Functional analysis of gene interaction networks is an important approach to identify genes whose expression is affected by one drug and that are at the same time known targets of other drugs already tested in humans for diverse disease conditions, thus pointing the latter as possible synergic drugs. Combined treatment with omeprazol increases the efficacy of praziquantel against S. mansoni adult worms in vitro, and additional in vivo studies are warranted. Two-condition experiment, PZQ-treated vs. untreated . Biological replicates: 2 with dye-swap
Project description:Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally-derived F2s, and identified a single QTL (LOD=31) on chromosome 6. A sulfotransferase was identified as the causative gene using RNAi knockdown and biochemical complementation assays and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for >99% of schistosomiasis cases worldwide. mRNA profiles from adult worms resistant (HR, 3 replicates) and susceptible (LE, 2 replicates) to the oxamniquine drug were compared to identify differential expression in genes related to drug resistance
Project description:Transcriptional profiling of Curcumin treated S. mansoni adult worms (15uM of Curcumin in DMSO during 24h) vs. Non-treated S.mansoni adult worms (DMSO during 24h)