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

适应性可塑性可以说是动物对抗日益严重的气候变化影响的最佳防御手段。然而，压力源的相互作用会破坏这种重要的防御。我的研究使用自下而上的方法来识别调节海葵（Nematostella vectensis）模型中对环境压力的塑料反应的信号通路。提出的工作还利用N. vectensis的克隆能力来测试可塑性是否带有固有的成本。我的第一个目标是确定调节塑料对热、渗透、缺氧和营养应激反应的分子途径。核受体（NRs）是整合环境输入与细胞反应的强有力的候选者，因为它们既是小分子受体，又是大规模转录网络的调节剂。我的实验室将研究三种贝氏螺旋体NRs: i)脊椎动物肝细胞核因子4a的同源物，ii)刺胞细胞特异性类视黄醇X受体亚家族成员，以及iii) Tailles亚家族成员。重要的是，这三种核糖核酸与许多动物系统的可塑性反应有关。我的实验室将对每种rna使用定制的转基因细胞系，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、氧合和营养可用性的变化。这一目标采用了我在高通量药物筛选方面的专业知识，但筛选的是环境压力因素。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）来预测显示可塑性生态成本的应激源相互作用。例如，如果给定的NR调节对热和渗透胁迫的反应，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)干扰协调对渗透应激反应的信号通路，或者b)诱导一种对渗透应激易感性增加的表型。通过量化野生收集的基因型的可塑性能力和测量生理性能特征（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增加生态成本。如果存在与可塑性相关的生态成本，我们可以预期，在可塑性能力最高的基因型中，性能性状受到的破坏最大。总的来说，这个项目将有助于提供一个预测框架来模拟可塑性的生态成本——这一目标在气候变化的影响下变得越来越重要。除了提供对NR信号和进化的更全面的理解之外，这项工作将有助于确定气候变化响应的新障碍，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.