OSIB: Neurobiology of Host Manipulation by Parasites

众所周知，寄生虫可以通过改变宿主的生理和行为来促进其生存和增殖。然而，在我们对寄生虫靶向修改其宿主神经系统的细胞和分子机制的理解中存在很大的差距。该项目探讨了寄生虫如何重新定向宿主的生殖能量，以满足其自身的生长和繁殖需求。实验将在双脐螺属的腹足类蜗牛上进行，双脐螺属是幼虫寄生性扁形虫的中间宿主。该项目响应NSF有机系统和感染生物学（OSIB）倡议的几个计划目标。它将为波多黎各大学的学生提供独特的机会，参与神经生物学，寄生虫学和全球健康前沿的研究。访问专家将介绍寄生虫生物学，基因编辑和神经成像技术的现代方法。 双脐螺属蜗牛感染幼虫寄生虫对发展中国家具有重大的社会经济影响，因为它在血吸虫病（一种普遍的热带贫困疾病）中起着不可或缺的作用。 因此，与埃及开罗的Theodor Bilharz研究所合作，扩大了学生参与者的视野，使他们了解全球科学发现方法的好处。该项目将增加来自代表性不足群体的科学家的人数，这些科学家接受培训，在神经生物学和寄生虫学的联系方面进行跨学科研究。它还将有助于形成一个日益意识到全球健康问题和挑战的公民群体。双脐螺属的淡水蜗牛是复殖吸虫曼氏血吸虫的中间宿主。在中间宿主体内，吸虫幼虫繁殖并转化为尾蚴，可以感染哺乳动物终末宿主。幼虫的增殖是通过宿主行为和生理的改变来促进的，包括被称为“寄生阉割”的繁殖减少。作为同时雌雄同体，每个双脐螺标本的雄性和雌性系统必须高度调节和协调。几种神经肽是控制腹足动物繁殖的信号系统之一。本研究探讨了两种神经肽，最近描述的Biomphalaria;促性腺激素释放激素相关肽，建议调节女性生殖系统和一个家庭的FMRF-NH 2相关肽，控制男性交配装置。神经肽的表达将在整个感染的开放前阶段进行研究。使用新型原位杂交技术（杂交链反应）检测编码肽前体的mRNA，并使用免疫组织化学定位成熟肽。通过FMRF-NH 2门控离子通道的突触信号传导将使用神经生理学方法在识别的神经元上进行研究。该项目响应NSF有机系统和感染生物学（OSIB）倡议的几个计划目标。拟议的实验将提供新的见解：1）感染过程的时间动态，2）在单个神经元水平上对宿主行为的寄生操纵，以及3）在研究不足的模型系统中免疫系统和神经系统之间的相互作用。该项目由BIO董事会的综合有机系统部门和刺激竞争研究的既定计划（EPSCoR）共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

It is well established that parasites can promote their survival and proliferation by altering the physiology and behavior of their hosts. Large gaps exist, however, in our understanding of the cellular and molecular mechanisms that parasites target to modify their host nervous systems. This project explores how parasites can redirect host reproductive energy to meet their own demands for growth and multiplication. Experiments will be performed on gastropod snails of the genus Biomphalaria, intermediate hosts for larval schistosome flatworms. This project responds to several programmatic objectives of the NSF Organismal Systems and Infection Biology (OSIB) initiative. It will provide students at the University of Puerto Rico with unique opportunities to participate in research at the cutting edge of neurobiology, parasitology, and global health. Visiting experts will present modern approaches to parasite biology, gene editing, and neuroimaging technologies. Infection of Biomphalaria snails by larval schistosomes has major socioeconomic implications for developing countries due to its obligatory role in schistosomiasis, a pervasive tropical disease of poverty. A collaboration with the Theodor Bilharz Research Institute in Cairo, Egypt, thus expands the horizons of student participants, exposing them to the benefits of a global approach to scientific discovery. This project will increase the number of scientists from underrepresented groups that are trained to conduct interdisciplinary research at the nexus of neurobiology and parasitology. It will also contribute to forming a citizenry that is increasingly aware of global health issues and challenges.Freshwater snails of the genus Biomphalaria serve as intermediate hosts for the digenetic trematode Schistosoma mansoni. Within the intermediate host, trematode larvae multiply and transform into the cercariae that can infect their mammalian definitive hosts. Larval proliferation is facilitated by modifications of host behavior and physiology, including a reduction of reproduction known as ‘parasitic castration’. As a simultaneous hermaphrodite, the male and female systems of each Biomphalaria specimen must be highly regulated and coordinated. Several neuropeptides are among the signaling systems that control gastropod reproduction. This study explores two neuropeptides that were recently described in Biomphalaria; a gonadotropin releasing hormone-related peptide that is proposed to regulate the female reproductive system and a family of FMRF-NH2 related peptides that control the male mating apparatus. Neuropeptide expression will be investigated across the prepatent phase of infection. The mRNA that encodes the peptide precursors will be detected using a novel in situ hybridization technique (Hybridization Chain Reaction) and the mature peptides will be localized with immunohistochemistry. Synaptic signaling through a FMRF-NH2 gated ion channel will be investigated using neurophysiological methods on identified neurons. This project responds to several programmatic objectives of the NSF Organismal Systems and Infection Biology (OSIB) initiative. The proposed experiments will provide new insights into 1) temporal dynamics of infectious processes, 2) parasitic manipulation of host behavior at the level of individual neurons, and 3) interactions between the immune and nervous systems in an under-studied model system. This project is funded jointly by Division of Integrative Organismal Systems in the BIO Directorate and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.