Decoding chemical communication in schistosomes

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Chemical communication is ubiquitous throughout the animal kingdom; it is used to mark territory, coordinate group behaviours as well as attract mates for sex. Although chemical dialogue has been extensively studied in invertebrates such as insects and nematodes, it remains enigmatic in the parasitic trematode Schistosoma spp. Schistosoma spp are unique in that they are the only trematodes to have separate sexes. They also illustrate a unique phenomenon in nature by the fact that the sexual maturation of female schistosomes is dependent on a constant pairing contact with the male. This constant pairing between male and female schistosomes is a prerequisite for egg production and the continuity of the life cycle. A variety of molecules have been shown to play essential roles in the biology and reproduction of schistosomes but the nature of the signals that stimulate female maturation are poorly understood. My long-term goal is to understand the molecular basis underlying the chemical dialogue in schistosomes with a focus on small molecule signals as well as their associated receptors that govern schistosome development and reproductive biology. There is evidence that a hormone-like molecule from male worms triggers the full growth and sexual maturation of the female worms. Pairing even controls the expression of female-specific expressed genes in the female reproductive organs. The presence of binding sites specific to a schistosome nuclear receptor (SmCAR) in the promoter of those genes suggests that SmCAR plays a role in the male-female interaction. Although schistosomes, like all worms, are unable to synthesize cholesterol and must obtain them from the host, there is evidence that male and female worms transferred cholesterol between each other. Male lipid extracts and excretory-secretory products stimulate sexual maturation in female worms suggesting that male stimulus is derived from cholesterol. We will focus on the role of SmCAR in S. mansoni and the nature of the stimulus that influences male-female interaction. Precisely, we will (aim 1) use functional genomics and RNA-seq to determine the function of SmCAR. Moreover, we will (aim 2) identify the target genes and ligands of SmCAR using ChIP-seq experiments and a mammalian cell-based assay to screen for putative ligands. Finally, we will (aim 3) determine the effects of cholesterol and metabolites of male worms on the reproduction of schistosomes. My studies will contribute to a better understanding of worm biology and how the host environment influences parasite development and reproduction. The outcomes of this research will significantly add to our understanding of the chemical communication in S. mansoni in the context of host-parasite and male-female interaction. This research plan will also provide training to 2 PhD and 3 MSc students in the field of host-parasite and parasite-to-parasite biology and experience in cellular and molecular biology and omics technologies.