NF-kappaB in Cnidarian Development

保守的NF-κ B转录因子信号转导途径控制多种生物体中的先天性免疫应答，但也控制某些无脊椎动物和脊椎动物系统中的发育细胞和组织命运。NF-#954;B通过控制编程发育命运的基因的表达来实现其生物学效应。本研究将探讨NF-#954;B如何在海洋动物中发挥作用。 拟议研究的结果将导致更好地了解一个关键分子途径（NF-#954;B）的进化基础，该途径被各种生物体用于免疫，发育和应激反应。它还将提供对这些信号通路如何通过发展或响应环境变化而演变和适应直接新的生物学结果的理解。 计划中的研究将对社会产生四大广泛影响。首先，该奖项将支持细胞和分子生物学，进化生物学，基因组学，计算生物学和发育生物学的跨学科培训，以博士，硕士和本科水平的学生，包括来自科学代表性不足的群体的学生。这种培训将提高STEM领域工作人员的科学能力。该项目的成果将扩大为广泛的研究社区服务的大量使用的互联网数据库。 研究人员还将开发额外的转录组和基因组资源，这将对其他研究无脊椎动物的研究人员有价值。 最后，从这些研究中获得的数据将有助于通过确定基础海洋生物发育和适应的分子机制，促进正在进行的海洋养护和管理工作。这些信息可以使科学家更好地评估环境威胁对主要沿海栖息地的指示物种的生物影响，例如所研究的模式生物Nematostella vectensis栖息的河口。该奖项支持涉及无脊椎动物模式生物Nematostella vectensis（Nv）的比较发育和分子研究的跨学科研究。这项研究将提供深入了解的功能NF-#954;B信号通路在刺胞发育和生物学意义的NF-#954;B的功能多态性存在于野生种群的NV。 将实现四个主要实验目标。(1)为了阐明上游NF-#954;B信号传导途径，将使用分子、细胞和整个动物测定来表征Nv中的其他信号传导蛋白。例如，I #954;B激酶和Toll样受体蛋白的组织和发育表达模式将使用免疫组织化学来确定。(2)NF-#954;B在门特异性细胞类型（刺胞）发育中的衍生作用将采用分子和生物学方法相结合的方法进行研究。(3)将通过计算预测和实验验证在发育细胞命运或其他生理过程中发挥作用的NF- #954;B的靶基因。(4)Nv的NF- #954;B蛋白中多态性的功能和生物学后果将使用蛋白质DNA结合位点微阵列技术以及生物学分析来确定。 研究结果将通过同行评审的科学出版物、会议演示和相关WWW网站提供，包括：StellaBase（stellabase.org）;线虫网络资源（nematostella.org）; NF-#954;B转录因子（www.nf-kb.org）。

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).