Characterizing gene regulatory networks that control gut-associated immunity

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We have analyzed immune diversity in genome sequences from a variety of animal phyla and find that different organisms have evolved a wide range of solutions to the problem of immune control. These diverse immune systems interface with shared gene regulatory circuitry structure. Characterizing the integration of these rapidly evolving recognition and effector systems with the more conserved core developmental gene regulatory networks, and the functional feedback between the two that maintains immune homeostasis is the focus of our laboratory. ******Rationale: An intact animal model with simple morphology provides a means to address these interactions. The purple sea urchin embryo/larva is a leading model for gene regulatory network biology and provides specific advantages for immune studies. The sea urchin is more closely related to vertebrates than other common invertebrate genetic models and shares an important genetic heritage with vertebrates. Sea urchin larvae are morphologically simple and transparent, which offers an unparalleled ability to visualize immune response at the resolution of individual cells. Furthermore, the transgenesis and gene perturbation techniques that are necessary for regulatory investigations can be performed with high efficiency.******Background: We have developed a novel model for characterization of the gut-associated immune response. After exposure to Vibrio diazotrophicus, larvae exhibit a robust, organism-wide response that involves the gut epithelium, immune cells and other tissues. The system returns to a quiescent state once bacteria are removed, allowing the study of both initiation and resolution of response. These events are accompanied by extensive changes in gene activity that we have thoroughly profiled using RNA-Seq. This model provides opportunities to mechanistically address problems of relevance to vertebrate inflammation, lineage-specific immune innovations and more general questions of immune system evolution. Here we will address the gene regulatory network connections that coordinate the larval gut-associated immune response, and how these feed into systems that maintain and renew immune cells.******PROJECT AIMS***1. Immune gene activity in the gut epithelium and control of IL17 in the initiation of response. ***2. Analysis of parallel and downstream regulatory inputs across response genes.******Significance and impact: A highly detailed understanding of animal immunity has only been achieved in vertebrates and arthropods. This work will lead towards a comprehensive view of the immune system in a third phylum. In doing so, it will broaden our view of animal immunology and identify regulatory interactions among gene homologs with direct relevance to vertebrates. In addition it will contribute to several areas of practical import such as aquaculture and the discovery of novel evolutionary innovations in microbial control strategies.