We study the physiological and evolutionary basis of osmotic stress acclimation and adaptation. The emphasis is on molecular evolution of osmotic stress tolerance in animals. We focus on aquatic animals as models because water salinity is a critical environmental parameter and can be precisely manipulated. We integrate osmotic stress responses of epithelial cells with the neuroendocrine (whole organism) stress response and also study relevant interactions of osmotic stress with other abiotic environmental stressors.

Intracellular signaling networks associated with environmental stress responses are very complex. Therefore, we focus on the identification and in-depth analysis of the major proteins (nodes) in the osmotic stress response network. Our two overall goals are 1) to reconstruct the osmotic stress signaling network starting from its major nodes; and 2) to understand how osmotic stress tolerance evolves. To best achieve these goals we selected tilapia and water fleas of the genus Daphnia as models according to the August Krogh principle. Broader evolutionary conservation of osmoprotective mechanisms identified in tilapia and daphnia is evaluated in mammalian kidney cells, other euryhaline fishes, and marine invertebrates.

Comparing osmotic stress effects with effects of other environmental stresses allows us to distinguish between general mechanisms of abiotic stress tolerance and stressor-specific mechanisms. Furthermore, we analyze responses over a range from mild to severe osmotic stress to understand how animals and their cells quantify stress and how acclimation and adaptation are matched to the degree of stress severity.

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Cells respond to environmental stress suich as osmotic stress in highly complex and integrated fashion. The molecular pathways activated in response to stress are robustly networked and tightly regulated. Stress response networks are largely based on changes in RNA and protein abundance, posttranslational protein modification, regulation of macro- and micromolecular interactions, and alteration of RNA and protein compartmentation. To model and better understand the osmoticl stress response network, detailed experimental data on the regulation of key network nodes are required. Combined with bioinformatics approaches that incorporate state-of-the-art network theory and knowledge classified in diverse gene ontology, interaction, and pathway databases such data will allow reconstruction of the osmotic stress response network.

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By using an evolutionary approach that utilizes conspecific and congeneric sister species as well as animals belonging to different phyla we aim to dissect nodes in the osmotic stress signaling network that are highly conserved and, therefore, represent cornerstones in the network. Such cornerstones would also be critical elements of osmotic stress response neytworks in humans. Consequently, our findings will advance knowledge of human conditions that are associated with abnormal plasma or tissue osmolality, including as fluid and electrolyte disorders, kidney diseases, hypertension, diabetes, and others. Comparing the regulation and function of such molecular cornerstones in different animals and under different environmental conditions provides valuable insight into how osmotic stress signaling networks operate and identifies targets for their manipulation.

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