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

Northwestern University, Evanston IL

Investigators

Abstract

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.