OSIB: Neurobiology of Host Manipulation by Parasites

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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.