Decoding chemical communication in schistosomes

破译血吸虫中的化学通讯

• 批准号: RGPIN-2020-05880
• 负责人: Long, Thavy
• 金额: $ 2.19万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=740888
• 关键词: Decoding; chemical; communication; schistosomes

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.

化学交流在整个动物王国中无处不在;它被用来标记领土，协调群体行为以及吸引配偶进行性行为。虽然化学对话已被广泛研究的无脊椎动物，如昆虫和线虫，它仍然是一个谜，在寄生吸虫血吸虫属血吸虫是独特的，因为他们是唯一的吸虫有单独的性别。它们还说明了自然界中的一个独特现象，即雌性双质体的性成熟依赖于与雄性的持续配对接触。这种雄性和雌性间的持续配对是产卵和生命周期连续性的先决条件。许多分子已被证明在染色体的生物学和生殖中发挥重要作用，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染色体中化学对话的分子基础，重点是小分子信号及其相关受体，这些受体控制染色体发育和生殖生物学。有证据表明，来自雄性蠕虫的一种类似精子的分子触发了雌性蠕虫的全面生长和性成熟。配对甚至控制雌性生殖器官中雌性特异表达基因的表达。在这些基因的启动子中存在特异性结合位点，表明SmCAR在雄性-雌性相互作用中起作用。虽然寄生虫像所有的蠕虫一样，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，雄性和雌性蠕虫相互转移胆固醇。雄虫的脂类提取物和排泄分泌物刺激雌蠕虫的性成熟，表明雄虫的刺激来自胆固醇。我们将重点关注SmCAR在S. mansoni和影响男女互动的刺激的性质。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鉴定SmCAR的靶基因和配体，以筛选推定的配体。最后，我们将（目的3）确定胆固醇和代谢产物的雄性蠕虫的生殖的影响。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。本研究的结果将大大增加我们对S. mansoni在宿主-寄生虫和男性-女性互动的背景下。该研究计划还将为2名博士和3名硕士学生提供宿主-寄生虫和寄生虫-寄生虫生物学领域的培训，以及细胞和分子生物学和组学技术方面的经验。