BBSRC-NSF/BIO: Regulatory control of the system-wide innate immune response in marine invertebrates

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Animals live in constantly changing environments that are rich in microbial life. The role of immune systems is to first recognize these microbes and then respond appropriately by either protecting the host or allowing the microbes to grow as part of a carefully regulated, mutually beneficial relationship. However, despite decades of research, the immune systems have been investigated in detail in only a few species (humans and mice). The proposed work will address this gap in knowledge by investigating immune responses in echinoderms, specifically the larval stages of sea urchins and sea stars. These larvae are morphologically simple, transparent animals that swim and feed in the ocean for several months prior to metamorphosis. In this project, which is a collaboration between researchers at Auburn University (US) and University College London (UK). Larvae will be exposed to specific marine bacteria that elicit immune responses. Infected larvae will be dissociated to single cells which will be used to measure changes in gene expression. These experiments will identify fundamental aspects of animal immune systems and identify novel strategies for treating disease. These scientific findings will be complemented with additional strategies to engage various segments of the broader community. This includes the development of marine-based workshops for elementary school students and participation in an interactive open house for middle- and high-school students from local under- resourced schools hosted at Auburn University. This work proposed here employs a collaborative approach that integrates recently available genome sequences with new technology for quantifying gene expression at single-cell resolution. This systems-level approach will define the regulatory mechanisms that control immune responses across different echinoderm species to identify fundamental properties of animal immunity as well as species-specific adaptations. By protecting the host from harmful pathogens and cultivating a beneficial microbiota, immune systems operate at the forefront of animal evolution. In response to rapidly evolving microbes, animals rely on sophisticated mechanisms for detecting and eliminating pathogens. These mechanisms are intertwined with host mechanisms for maintaining cellular homeostasis and resolving stress. The aim of this proposal is to understand how evolutionary pressures shape the cells that mediate immune response. This work builds on the well-characterized immune responses in purple sea urchin (Strongylocentrotus purpuratus) larvae by extending these findings to additional echinoderm species at varying phylogenetic distances. Cellular immune responses of echinoderm larvae exposed to bacterial and viral pathogens will be characterized using microscopy and by profiling system-wide changes in gene expression using single-cell RNA-Seq. Network modeling approaches will be used to predict regulatory linkages that control immune responses. Candidate linkages will be confirmed using in vivo perturbation assays. This innovative analysis will reveal evolutionarily conserved principles of immune response as well as species-specific adaptations. This collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.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.