LiT: Rel Homology Domain Signal Transduction Pathways in the Sea Anemone Nematostella vectensis

所有生物的生存取决于它们管理环境压力的能力，无论是由物理因素（例如，热、氧、化学品）或生物（例如，病原体）损伤。 许多动物，包括昆虫和脊椎动物，通过激活一个保守的分子途径，称为NF-κ B转录因子信号转导途径，对广泛的环境压力作出反应。 虽然NF-κ B通路是许多高等动物应激反应系统的关键，但其进化起源尚不清楚。 在目前的项目中，编码许多与人类NF-κ B途径相似的关键蛋白质的基因已经在一种简单的海洋生物中被鉴定和克隆，即星海葵Nematostella vectensis（刺胞动物门）。该项目涉及分子进化生物学家（Finnerty）和细胞分子生物学家（Gilmore）之间的跨学科研究，旨在深入了解NF-kappaB信号通路的祖先功能，以及NF-kappaB基因变体的生物学和生态学意义，该基因变体存在于Nematostella的野生种群中。 具体而言，本研究正在研究NF-kappaB在简单海洋动物中的功能，并将实现三个主要实验目标。 (1)NF-κ B信号蛋白的特点是在海葵Nematostella使用各种分子，细胞，和整个动物测定。 (2)NF-kappaB调控的基因和能够激活NF-kappaB及其靶基因的应激物将在线虫中被鉴定。 (3)Nematostella的NF-κ B蛋白的基因变体的功能和选择性后果将被确定。 更广泛的影响这项研究将导致更好地了解当代动物应激反应途径的进化起源，以及更好地了解这些途径如何在应对环境变化（气候变化，新的物理/化学损伤，新的病原体）时进化。 该研究计划将产生三大更广泛的影响。 它将为博士和本科生提供细胞和分子生物学，进化生物学，基因组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。 它将加强为广大研究界服务的三个使用率很高的因特网数据库：StellaBase（http：stellabase.org）; Nematostella网络资源（http：nematostella.org）;和Rel/NF-κ B转录因子（http：www.nf-kb.org）。 它将通过确定环境压力的分子标记，为正在进行的海洋保护工作作出贡献。 这些资料可使养护科学家更好地监测影响主要沿海生境中指标物种的环境威胁的生物影响，例如海葵Nematostella栖息的沿海河口。

The survival of all organisms depends on their ability to manage environmental stress, whether caused by physical (e.g., heat, oxygen, chemicals) or biological (e.g., pathogens) insult. Many animals, including insects and vertebrates, respond to a wide range of environmental stresses by activating a conserved molecular pathway, called the NF-kappaB transcription factor signal transduction pathway. Although the NF-kappaB pathway is critical for many higher animal stress response systems, its evolutionary origins are obscure. In the current project, genes encoding many key proteins similar to the human NF-kappaB pathway have been identified and cloned in a simple marine organism, the starlet sea anemone Nematostella vectensis (phylum Cnidaria). This project involves interdisciplinary research between a molecular evolutionary biologist (Finnerty) and a cell & molecular biologist (Gilmore) that seeks to gain insights into the ancestral function of the NF-kappaB signaling pathway, and the biological and ecological significance of a gene variant of NF-kappaB that exists in wild populations of Nematostella. Specifically, this research is investigating how NF-kappaB functions in simple marine animals, and three major experimental aims will be accomplished. (1) NF-kappaB signaling proteins are being characterized in the sea anemone Nematostella using a variety of molecular, cellular, and whole animal assays. (2) Genes regulated by NF-kappaB and stressors that can activate NF-kappaB and its target genes will be identified in Nematostella. (3) The functional and selective consequences of gene variants of the NF-kappaB protein of Nematostella will be determined. Broader ImpactsThe research will lead to a better understanding of the evolutionary origins of the stress response pathways of contemporary animals, and a better understanding of how these pathways can evolve in response to environmental change (climatic shifts, new physical/chemical insults, novel pathogens). The research program will have three major broader impacts. It will provide interdisciplinary training in cell and molecular biology, evolutionary biology, genomics, and developmental biology to students at the PhD and undergraduate levels, including students from groups that are under-represented in science. It will augment three heavily utilized Internet databases that serve a broad research community: StellaBase (http://stellabase.org); The Nematostella Web Resource (http://nematostella.org); and Rel/NF-kappaB Transcription Factors (http://www.nf-kb.org). It will contribute to ongoing marine conservation efforts by identifying molecular markers for environmental stressors. Such information may better enable conservation scientists to monitor the biological effects of environmental threats impacting indicator species in key coastal habitats, such as the coastal estuaries inhabited by the sea anemone Nematostella.