20-BBSRC/NSF-BIO Regulatory control of innate immune response in marine invertebrates

Animals live in constantly changing environments that are rich in microbial life. Immune systems orchestrate the complex, dynamic relationships between animals and microbes by both eliminating pathogenic microbes as well as promoting the growth of beneficial microbiota. However, our understanding of innate immune mechanisms in most animal phyla, including vertebrates, remains limited. The proposed research addresses this considerable knowledge gap by exploiting the experimental advantages of echinoderm larvae to investigate immune responses in a relatively unexplored animal lineage. Echinoderm larvae are morphologically simple, free-swimming multicellular organisms equipped with a sophisticated cellular and molecular immune system. By integrating recently available sequencing data from several echinoderm species with technology for measuring gene expression at single-cell resolution, the proposed research will significantly advance our understanding of animal immunity. This proposal describes a collaborative, systems-level approach to define the regulatory mechanisms that control immune responses across different echinoderm species. This innovative analysis will reveal evolutionarily conserved principles of immune response as well as species-specific adaptations.

Animals live in constantly changing environments that are rich in microbial life. Immune systems orchestrate the complex, dynamic relationships between animals and microbes by both eliminating pathogenic microbes as well as promoting the growth of beneficial microbiota. However, our understanding of innate immune mechanisms in most animal phyla remains limited. The proposed research will address this knowledge gap by exploiting the experimental advantages of echinoderm larvae to investigate immune responses.
The proposed work will investigate immunity in four echinoderm species and characterising the response to both bacterial and viral pathogens. The echinoderm species were selected to reflect a range of taxonomic distances, ecological niches, and life history traits. The proposed work will be carried out in three aims. First, larval immune cell populations will be defined using in vivo microscopy and functional assays. Second, the change in gene activity in response to immune challenge will be measured both system-wide and at single-cell resolution using high throughput sequencing techniques. Findings from these two experimental strategies will be integrated to construct gene regulatory networks (GRNs) that regulate innate immune response. Regulatory linkages will be validated using in vivo perturbation assays.
Findings will delineate the system-wide transcriptional response to immune perturbation in higher temporal and cellular resolution than is possible in any other experimental systems. This work will substantially expand our understand of animal immunity. Furthermore, a phylogenetic perspective will generate a systems-level framework for understanding how immune systems evolve. This original and innovative approach will uncover fundamental properties of immune responses to different type of pathogens.