NF-kappaB in Cnidarian Development

Trustees Of Boston University, Boston

Investigators

Abstract

The conserved NF-κB transcription factor signal transduction pathway controls innate immune responses in a variety of organisms, but also controls developmental cell and tissue fates in certain invertebrate and vertebrate systems. NF-κB carries out its biological effects by controlling the expression of genes that program developmental fate. This research will investigate how NF-κB functions in basal marine animals. The results of the proposed research will lead to a better understanding of the evolutionary underpinnings of a key molecular pathway (NF-κB) that is used by a variety of organisms for immunity, development and stress responses. It will also provide an understanding of how such signaling pathways can evolve and adapt to direct novel biological outcomes through development or in response to environmental changes. The planned studies will have four major broader impacts for society. First, the award will support interdisciplinary training in cell and molecular biology, evolutionary biology, genomics, computational biology, and developmental biology to students at the PhD, Masters and undergraduate levels, including students from groups underrepresented in science. Such training will enhance the scientific competence of the STEM field workforce. Results form the project will augment heavily utilized Internet databases that serve a broad research community. The investigators will also develop additional transcriptomic and genomic resources that will be valuable for other researchers studying invertebrate animal. Finally, data from these studies will contribute to ongoing marine conservation and management efforts by identifying molecular mechanisms underlying basal marine organism development and adaptation. Such information may better enable scientists to assess biological effects of environmental threats impacting indicator species in key coastal habitats, such as estuaries inhabited by the studied model organism, the sea anemone Nematostella vectensis. This award supports interdisciplinary research involving an invertebrate model organism, the sea anemone Nematostella vectensis (Nv), in comparative developmental and molecular studies. The research will provide insights into the function of the NF-κB signaling pathway in cnidarian development and the biological significance of a functional polymorphism in NF-κB that exists in wild populations of Nv. Four major experimental aims will be accomplished. (1) To elucidate upstream NF-κB signaling pathways, additional signaling proteins will be characterized in Nv using molecular, cellular, and whole animal assays. For example, the tissue and developmental expression patterns of IκB Kinase and Toll-like Receptor proteins will be determined using immunohistochemistry. (2) The derived role of NF-κB in the development of a phylum-specific cell type, the cnidocyte, will be investigated using combined molecular and biological approaches. (3) Target genes of NF-κB that play roles in developmental cell fate or other physiological processes will be computationally predicted and experimentally validated. (4) The functional and biological consequences of polymorphisms in the NF-κB protein of Nv will be determined using a protein DNA binding-site microarray technology, as well as biological analyses. Results from the studies will be made available through peer-reviewed scientific publications, presentations at meetings, and through relevant WWW-sites, including: StellaBase (stellabase.org); The Nematostella Web Resource (nematostella.org); and NF-κB Transcription Factors (www.nf-kb.org).