Mechanisms and Costs of Adaptive Plasticity in a Starlet Anemone (Nematostella Vectensis) Model

可以说，适应性可塑性代表了动物对气候变化日益加剧的影响的最好防御。然而，压力因素的相互作用可能会破坏这一重要的防御。我的研究使用自下而上的方法，在海葵(Nematostella Vetensis)模型中识别调节塑料对环境压力反应的信号通路。这项拟议的工作还利用矢状核线虫的克隆能力来测试可塑性是否具有内在成本。我的第一个目标是确定调节塑料对热、渗透、低氧和营养应激反应的分子途径。核受体是将环境输入与细胞反应相结合的有力候选者，因为它们既是小分子受体又是大规模转录网络的调节者。我的实验室将研究三个媒介鼻炎NRs：i)脊椎动物肝细胞核因子4a的同源基因，ii)脊椎动物特有的维甲酸X受体亚家族成员，以及iii)尾巴亚家族成员。重要的是，在许多动物系统中，这三种NRs与塑料反应有关。我的实验室将使用定制的转基因株系来测试它们的表达水平、DNA结合动力学、蛋白质相互作用网络和活动模式如何响应温度、盐度、氧气和营养可获得性的变化。这个目标利用了我在高通量药物筛选方面的专业知识--但却是为了筛选环境应激源。我的第二个目标将使用信号通路中的重叠(在目标1中确定)来预测显示可塑性的生态成本的应激源相互作用。例如，如果给定的NR同时调节对热胁迫和渗透胁迫的反应，我们预计某些温度-盐度组合可能会破坏可塑性。例如，热应激可能a)堵塞协调渗透胁迫反应的信号通路，或b)诱导对渗透胁迫易感性增加的表型。通过量化野生收集的基因类型的可塑性能力并测量生理表现特征(即代谢率、发育率、生长率)，我的实验室可以测试特定应激源的相互作用是否会促进生态成本。如果存在与可塑性相关的生态成本，我们预计表现性状在具有最高可塑性能力的基因型中受到的干扰最大。总体而言，该项目将帮助提供一个预测框架，以对可塑性的生态成本进行建模--这一目标在气候变化的影响下变得越来越关键。除了提供对NR信号和进化的更全面的了解外，这项工作还将有助于识别应对气候变化的新障碍，并有助于确定可塑性是否足以克服动物面临的日益复杂和快速的环境变化。

Adaptive plasticity arguably represents the best defense animals have against the mounting effects of climate change. However, stressor interactions can undermine this important defense. My research uses a bottom-up approach to identify the signaling pathways that regulate plastic responses to environmental stress in a starlet anemone (Nematostella vectensis) model. The proposed work also capitalizes on the clonal ability of N. vectensis to test whether plasticity carries inherent costs. My first objective seeks to identify the molecular pathways that regulate plastic responses to thermal, osmotic, hypoxic, and nutritional stress. Nuclear receptors (NRs) represent strong candidates to integrate environmental inputs with cellular responses because they function both as small molecule receptors and regulators of large-scale transcriptional networks. My lab will investigate three N. vectensis NRs: i) an ortholog of vertebrate hepatocyte nuclear factor 4a, ii) a cnidarian-specific retinoid X receptor subfamily member, and iii) a Tailles subfamily member. Importantly, these three NRs have been associated with plastic responses in a number of animal systems. Using custom transgenic lines for each of these NRs, my lab will test how their expression levels, DNA-binding dynamics, protein-interaction networks, and activity patterns respond to shifts in temperature, salinity, oxygenation, and nutrient availability. This objective co-opts my expertise in high-throughput drug screening - but to screen for environmental stressors instead. My second objective will use overlaps in signalling pathways (identified in objective 1) to predict stressor interactions that manifest ecological costs of plasticity. For example, if a given NR regulates responses to both thermal and osmotic stress, we would expect that certain temperature-salinity combinations could undermine plasticity. Thermal stress, for instance, might a) jam the signaling pathways that coordinate responses to osmotic stress, or b) induce a phenotype that has increased vulnerability to osmotic stress. By quantifying the capacity for plasticity in wild-collected genotypes and measuring physiological performance traits (i.e., metabolic rate, developmental rate, growth rate), my lab can test whether specific stressor interactions promote ecological costs. If there are ecological costs associated with plasticity, we would expect performance traits to be most disrupted in genotypes with the highest capacities for plasticity. Collectively, this program will help provide a predictive framework to model the ecological costs of plasticity - a goal that is increasingly critical with the effects of climate change. In addition to providing a more comprehensive understanding of NR signalling and evolution, this work will help identify novel barriers to climate change responses and help determine whether plasticity will be enough to overcome the increasingly complex and rapid changes in environment animals face.