Decoding chemical communication in schistosomes

在动物王国里，化学通讯无处不在；它被用来标记领地，协调群体行为，以及吸引异性交配。虽然化学对话在昆虫和线虫等无脊椎动物中得到了广泛的研究，但在寄生吸虫血吸虫中仍然是一个谜。血吸虫是唯一具有独立性别的吸虫。它们还说明了自然界中一个独特的现象，即雌性血吸虫的性成熟依赖于与雄性血吸虫的持续配对接触。雄性和雌性血吸虫之间的这种不断配对是产卵和生命周期连续性的先决条件。多种分子已被证明在血吸虫的生物学和繁殖中发挥重要作用，但刺激雌性成熟的信号的性质却知之甚少。我的长期目标是了解血吸虫化学对话的分子基础，重点研究控制血吸虫发育和生殖生物学的小分子信号及其相关受体。有证据表明，雄性蠕虫体内的一种激素样分子会触发雌性蠕虫的完全生长和性成熟。配对甚至控制了雌性生殖器官中雌性特异性表达基因的表达。在这些基因的启动子中存在血吸虫核受体（SmCAR）特异性结合位点，表明SmCAR在雌雄相互作用中起作用。虽然血吸虫和所有蠕虫一样，不能合成胆固醇，必须从宿主那里获得胆固醇，但有证据表明，雄性和雌性蠕虫可以相互传递胆固醇。雄性脂质提取物和排泄产物刺激雌性蠕虫的性成熟，表明雄性刺激来自胆固醇。我们将重点关注SmCAR在S. mansoni中的作用以及影响男女相互作用的刺激的性质。准确地说，我们将（目标1）使用功能基因组学和RNA-seq来确定SmCAR的功能。此外，我们将（目标2）使用ChIP-seq实验和基于哺乳动物细胞的测定来筛选假定的配体，以确定SmCAR的靶基因和配体。最后，我们将（目标3）确定胆固醇和雄性蠕虫代谢物对血吸虫繁殖的影响。我的研究将有助于更好地了解蠕虫生物学以及宿主环境如何影响寄生虫的发育和繁殖。本研究结果将显著增加我们对mansoni在宿主-寄生虫和雄性-雌性相互作用背景下的化学通讯的理解。该研究计划还将为宿主-寄生虫和寄生虫-寄生虫生物学领域的2名博士和3名硕士学生提供培训，并提供细胞和分子生物学和组学技术方面的经验。

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.