The Molecular Characterization of Evolutionarily Conserved Immune Cell Populations and Immune Mediators in Invertebrates

Within the chordate phylum vertebrates emerged during evolution from an invertebrate ancestor. In addition to the invention of vertebrae that gave this subphylum its name, a novel feature in the host defense mechanism arose: adaptive immunity. This arm of the immune system provides a tremendous boost to the underlying innate immune system in the form of immune memory and pathogen-specificity of the immune receptors. To understand fundamental aspects of how the innate and adaptive immune system interact, it is critical to gain insight into the state of the ancestral innate immune systems on top of which adaptive immune mechanisms emerged. In recent work we discovered that the genome of Strongylocentrotus purpuratus (purple sea urchin), an invertebrate, encodes homologs of several proteins previously thought to be exclusive to vertebrate immunity including the two enzymes that initiate the somatic gene diversification processes critical for immunoglobulin and T cell receptor diversity. Hence the overarching goal of this proposal is to lay the foundation for a comprehensive characterization of the S. purpuratus immune system. We will complement the existing morphological characterization of its immune cells with the underlying gene expression profiles and the analyses of the respective transcriptomes will provide insight into the relationship to mammalian immune cell populations. This work will be complemented by functional studies of two putative ancestral innate immune mediators whose existence outside of vertebrates had not been previously anticipated: (1) novel members of the AID/APOBEC family of polynucleotide cytidine deaminases important for both, high-affinity immunoglobulin and innate antiviral responses, and (2) homologs of the mediators of pyroptotic cell death in response to intracellular pathogens. Together these studies will not only provide a broad view of the immune system of this non-model organism, but also important insight into two ancestral evolutionarily conserved defense mediators descendants of which are still key contributors to human immune responses.

Project ID:PC10901-0799
External Project ID:MOST108-2320-B182-018-MY3