Welcome to the ICOPA 2022 Online Program

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Urogenital schistosomiasis is caused by Schistosoma haematobium and is one of the most neglected tropical diseases worldwide. It is characterised by granulomata and fibrosis in urogenital tissues, and increased susceptibility to HIV/AIDS and cancer of the bladder. To break the transmission of disease, sound knowledge and understanding of the biology of S. haematobium is required. Hybridisation/introgression events and molecular variation among members of the S. haematobium-group might effect important biological and/or disease traits as well as the morbidity of disease and the effectiveness of control programs including mass drug administration. Here we report the first chromosome-contiguous genome for a well-defined laboratory line of this blood fluke. An exploration of this genome using transcriptomic data for all key developmental stages allowed us to refine gene models (including non-coding elements) and annotations, discover ‘new’ genes and transcription profiles for these stages, likely linked to development and/or pathogenesis. Molecular variation among S. haematobium worms revealed unique genomic ‘signatures’ that matched species other than S. haematobium, indicating the occurrence of introgression events. The reference genome and the findings from this study underpin future functional genomic and molecular investigations of schistosomes and accelerate systematic, large-scale population genomics investigations, with a focus on control of schistosomiasis.

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For diseases such as malaria we have a well characterized set of genetic markers that can provide a rapid drug resistance profile of the drug resistance phenotype of parasites. These markers can be used to determine optimal treatments for patients, and to monitor and manage resistance spread. Our central goal is to develop comparable field-applicable tools for schistosome parasites. To do this we use a variety of genetic mapping approaches to determine genes that underlie resistance in field or laboratory parasite populations. This has led to the identification of mutations in a sulfotransferase underlying oxamniquine resistance and markers in a transient receptor potential channel associated with reduced praziquantel response. We are now developing both phenotype and genotype based methods for screening for drug resistant parasites in the field. We believe that surveillance of this nature is essential given the ramping up of efforts to control schistosomiasis, and consequent increased selection for drug resistance.

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Amongst the most remarkable features of schistosome biology is the dependence of the sexual maturation of adult females from constant pairing contacts with males. Only pairing leads to the differentiation of female gonads, and finally to egg production. In contrast, males are sexually mature before pairing, with fully developed testes and sperm production. Although long known, our understanding of schistosome reproductive biology and its underlying molecular principles is still fragmentary.

By organ-isolation and subsequent comparative sub-transcriptomics with RNA of adults and gonads of both paired and unpaired adult S. mansoni, we identified transcripts of >7,000 genes in both sexes. Of these, many transcripts occurred pairing-dependently, 3,600 in ovaries and 243 in testes. This indicated a bidirectional influence of pairing of both genders. Bioinformatics analyses provided new insights into the potential roles of GPCRs and neuropeptides in schistosome development and differentiation. Besides a new description of the GPCRome of S. mansoni, based on genome version 7, we found few gonad-preferentially transcribed GPCRs and many others transcribed with a male-bias without testes expression. This applied also to the transcript profiles of predicted neuropeptides. After the successfully establishment of the innovative MALAR yeast two-hybrid system to associate neuropeptide ligands with their cognate receptors, we identified putative neuropeptides for some of these GPCRs, which were differentially expressed in a gender-, tissue, and/or pairing-dependent manner in males. By functional analyses using RNAi and localization studies we found evidence for neuronal localization of GPCRs/neuropeptides and their putative roles in either spermatogenesis in the male or egg production in the paired female, respectively. From these data, we conclude that male-female interaction of schistosomes is more complex than envisaged before. Furthermore, GPCRs and neuropeptides may play important roles for male-female interaction of S. mansoni and the pairing-dependent as well as neuronal activity-mediated control of reproductive processes.

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Mass-drug administration (MDA) using praziquantel monotherapy has become the primary strategy for the control and elimination of the neglected tropical disease schistosomiasis. To understand how long-term MDA is impacting the transmission and evolution of schistosome populations, we analysed whole-genome sequence data of 574 Schistosoma mansoni and S. rodhaini accessions from eight countries. We observed high genetic diversity and widespread transmission of S. mansoni lineages within and between major foci of infection. Within Lake Victoria, a transmission hotspot, we found evidence of recent hybridization between the human- and rodent-infective S. mansoniand the rodent-infective S. rodhaini, with indications of introgression of S. rodhaini alleles into S. mansoni populations. Analysis of candidate praziquantel resistance loci identified several rare and low-frequency variants, predicted to reduce praziquantel sensitivity, in population sampled from regions of long-term MDA. Our findings provide insights into the genomic composition of endemic populations and should help inform genomic surveillance of this major human parasite.