Collaborative Research: RUI: Uncovering the Role of Sirtuins in Linking Food Availability and Stress Tolerance Through Multi-Scale Signaling Networks in Mussels

合作研究：RUI：通过贻贝中的多尺度信号网络揭示 Sirtuins 在连接食物供应和应激耐受性方面的作用

• 批准号: 1557500
• 负责人: Lars Tomanek
• 金额: $ 59.15万
• 依托单位: California Polytechnic State University Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1557500&HistoricalAwards=false
• 关键词: Collaborative; Research; RUI; Uncovering; Role

One of the major aims of biology is to explain how changes that occur at the sub-cellular level affect the function at higher levels of biological organization, such as organs or the whole organism. Specifically, how are changes in the expression of genes and proteins, and the concentration of metabolites of a cell, affecting the organ of which the cell is a part? Furthermore, when do these changes in organ function affect properties of the whole organism? Using the California mussel Mytilus californianus, we ask, when do subcellular changes in gill cells affect feeding rate or changes in muscle biochemistry affect the ability to close their shells? We aim to address these questions by collecting data from different levels of biological organization simultaneously, from the subcellular to the organ and organism levels in response to relevant environmental stressors, such as food availability, heat stress and the inhibition of signaling pathways. The investigators' expertise in comparative environmental physiology and computational mathematics will enable them to address the relevance of subcellular changes to predict organ and organism level changes using a mathematical model. The proposal has a strong training component and is centered on lowering the barriers to molecular and computational technologies and building a diverse community of young scientists in integrative organismal biology. Furthermore, K-12 resources will be developed on the physiological impacts of future environmental change that align with Common Core and Next Generation Science Standards.The specific objective of this study is to develop quantitative, predictive models that uncover the underlying interactions/regulations among subcellular networks (transcriptomic, metabolomic and proteomic or TMP) and their effect at the phenotypes of the organ and organism in response to environmentally relevant stressors (i.e., low/high food availability and low/high body temperature), based on high-throughput experimental data, in the intertidal mussel Mytilus californianus. The experimental design will also focus on testing a possible mechanistic link between food availability and stress tolerance by inhibiting signaling pathways involving sirtuins, which are deacylases that respond to caloric restriction and stress. This proposal distinguishes itself from previous studies on the thermal physiology of intertidal organisms in that it incorporates statistical models (including regression and decision trees) to uncover the regulatory structure of the TMP networks and determine whether the resulting topology accurately predicts observed phenotypic responses measured at the organ and whole organism levels. The PIs' complementary expertise in TMP analyses, integrative biology and computational modeling will enable them to combine "omics" technologies, organismal physiology and computational approaches to advance integrative organismal biology. The PIs are planning to disseminate the modeling framework through a research coordination network (RCN) on Integrative Organismal Biology. The results will improve our ability to predict how mussels will respond to future environmental change and thereby improve our understanding of the role of mussel aquaculture in providing a secure and sustainable food resource in the future.

生物学的主要目的之一是解释在细胞层面上发生的变化如何影响较高的生物组织（例如器官或整个生物体）的功能。具体而言，基因和蛋白质表达的变化以及细胞的代谢产物的浓度如何影响细胞是一部分的器官？ 此外，器官功能的这些变化何时会影响整个生物的性质？ 我们问，使用加利福尼亚贻贝mytilus加利福尼亚州，g细胞的亚细胞变化何时会影响进食率或肌肉生物化学的变化会影响关闭其壳的能力？我们的目标是通过同时收集来自不同水平的生物组织的数据，从亚细胞到器官和生物水平，以响应相关的环境压力源，例如食物的可用性，热应激和信号传导途径的抑制。研究者在比较环境生理学和计算数学方面的专业知识将使他们能够通过数学模型来解决细胞下变化对预测器官和生物水平变化的相关性。该提案具有强大的培训组成部分，并以降低分子和计算技术的障碍，并在综合生物学中建立了多样化的年轻科学家社区。此外，K-12资源将基于与共同核心和下一代科学标准相符的未来环境变化的生理影响的发展。本研究的具体目标是开发定量的，预测的模型，这些模型可以揭示潜在的相互作用/法规，从而在下细胞网络之间（转录，新生组和蛋白质或TMP）及其响应的响应效应，并在现象中构成了现象的效应。 （即，基于高通量的实验数据，在潮间带Mytilus Californianus中，基于高通量实验数据，低/高食物的可用性和低/高体温）。实验设计还将集中于通过抑制涉及Sirtuins的信号通路来测试食物可利用性和应激耐受性之间的可能机械联系，涉及Sirtuins的信号通路是对热量限制和压力反应的脱酰基酶。该提案将自己与先前关于潮间生物的热生理的研究区分开来，因为它结合了统计模型（包括回归和决策树），以发现TMP网络的调节结构，并确定所得拓扑是否准确地预测观察到的观察到的表型在器官和整个生物体水平上测量的表型反应。 PI在TMP分析中的补充专业知识，综合生物学和计算建模将使它们能够结合“ OMICS”技术，生物生理学和计算方法，以推进整合性生物学。 PI正在计划通过综合生物学的研究协调网络（RCN）传播建模框架。结果将提高我们预测贻贝将如何应对未来环境变化的能力，从而提高我们对贻贝水产养殖在将来提供安全可持续的食物资源中作用的理解。