OSIB: Neurobiology of Host Manipulation by Parasites

OSIB：寄生虫操纵宿主的神经生物学

• 批准号: 2217657
• 负责人: Mark Miller
• 金额: $ 35.04万
• 依托单位: University of Puerto Rico Medical Sciences Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2217657&HistoricalAwards=false
• 关键词: OSIB; Neurobiology; Host; Manipulation; Parasites

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.

众所周知，寄生虫可以通过改变宿主的生理和行为来促进它们的生存和繁殖。然而，在我们对寄生虫以改变宿主神经系统为目标的细胞和分子机制的理解方面存在着很大的差距。这个项目探索寄生虫如何改变宿主的生殖能量，以满足自己对生长和繁殖的需求。实验将在Biomphalaria属的腹足类蜗牛上进行，Biomphalaria是血吸虫幼虫的中间宿主。该项目响应了NSF组织系统和感染生物学(OSIB)倡议的几个规划目标。它将为波多黎各大学的学生提供参与神经生物学、寄生虫学和全球卫生前沿研究的独特机会。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。由于血吸虫病是一种普遍存在的热带贫困疾病，由于血吸虫病对发展中国家具有重大的社会经济影响，因此幼虫感染钉螺对发展中国家具有重大的社会经济影响。因此，与埃及开罗的西奥多·比尔哈兹研究所合作，扩大了学生参与者的视野，使他们接触到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人数，他们接受培训，在神经生物学和寄生虫学的结合点进行跨学科研究。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。生物吸虫属淡水蜗牛是双基因吸虫曼氏血吸虫的中间宿主。在中间宿主内，吸虫幼虫繁殖并转化为尾蚴，可以感染它们的哺乳动物最终宿主。幼虫的繁殖是通过改变寄主行为和生理来促进的，包括减少繁殖，这种现象被称为“寄生阉割”。作为同时的两性生物，每个生物软体标本的雄性和雌性系统必须受到高度的调节和协调。有几种神经肽是控制腹足类繁殖的信号系统之一。这项研究探索了最近在Biomphalaria中描述的两种神经肽：一种是被认为调节雌性生殖系统的促性腺激素释放激素相关肽，另一类是控制雄性交配器官的FMRF-NH2相关肽。神经肽的表达将在感染的潜伏期前进行研究。编码多肽前体的mRNA将通过一种新的原位杂交技术(杂交链式反应)进行检测，成熟多肽将通过免疫组织化学进行定位。通过FMRF-NH2门控离子通道的突触信号将在已识别的神经元上使用神经生理学方法进行研究。该项目响应了NSF组织系统和感染生物学(OSIB)倡议的几个规划目标。拟议中的实验将为1)感染过程的时间动力学，2)在单个神经元水平上寄生操纵宿主行为，以及3)在一个未被研究的模型系统中免疫系统和神经系统之间的相互作用提供新的见解。该项目由BIO理事会中的综合组织系统部门和既定的激励竞争研究计划(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智力优势和更广泛的影响审查标准进行评估，被认为值得支持。