NF-kappaB in Cnidarian Development

保守的转录因子信号转导通路控制着多种生物的先天免疫反应，但也控制着某些无脊椎动物和脊椎动物系统中发育细胞和组织的命运。核因子-B通过控制控制发育命运的基因的表达来实现其生物学效应。这项研究将调查核因子-B如何在基础海洋动物中发挥作用。拟议的研究结果将有助于更好地理解一种关键分子途径(核因子-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育或响应环境变化来进化和适应直接的新生物结果的理解。计划中的研究将对社会产生四大更广泛的影响。首先，该奖项将支持对博士、硕士和本科生在细胞和分子生物学、进化生物学、基因组学、计算生物学和发育生物学方面的跨学科培训，包括来自科学代表性不足的群体的学生。这种培训将提高科学、技术和经济研究领域外地工作人员的科学能力。该项目的结果将增加大量使用的互联网数据库，为广泛的研究社区服务。研究人员还将开发更多的转录和基因组资源，这对其他研究无脊椎动物的研究人员将是有价值的。最后，这些研究的数据将通过确定基础海洋生物发展和适应的分子机制，为正在进行的海洋养护和管理工作作出贡献。这些信息可能使科学家能够更好地评估环境威胁对关键沿海生境中指示物种的生物影响，例如所研究的模式生物海葵所栖息的河口。该奖项支持在比较发育和分子研究中涉及无脊椎动物模式生物海葵的跨学科研究。这项研究将对NV野生种群中存在的NF-&B信号通路在线虫发育中的功能以及存在的功能多态的生物学意义提供见解。将实现四个主要的实验目标。(1)为了阐明上游的核因子-B信号通路，将使用分子、细胞和整个动物分析来鉴定NV中的其他信号蛋白。例如，I&Amp；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)将用分子和生物学相结合的方法研究核因子-B在一种门特定细胞类型--神经细胞的发育中的衍生作用。(3)在发育细胞命运或其他生理过程中发挥作用的核因子B的靶基因将通过计算预测和实验验证。(4)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NV核因子-B蛋白多态的功能和生物学后果。研究结果将通过同行评议的科学出版物、会议上的陈述以及相关的WWW网站公布，包括：StellaBase(stellabase.org)；Nematostella网络资源(nematostella.org)；和NF-&amp；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).