SPATIAL DOMAINS IN SIGNALING NETWORKS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this project is to study the role of morphology and spatial anisotropy in regulating intracellular signaling. The intracellular signal transducing process often involves the local production of small molecule messengers and the local activation of protein kinases, protein phosphatases and other signaling components. It has long been thought that some of the specificity observed in the effects of signals that use similar or identical signaling pathways arise from such spatial domains of signaling components within the cells. submembrane cytosolic. Understanding the origins and dynamics of spatial domains is very important for unraveling cellular complexity, since response to information flow within the cell is directly dependent on spatial specifications. The overall approach for this project is to developed spatially-specified partialdifferential equation-based models using realistic cell shape and location of relevant components. These models are being developed using the Virtual Cell to explore the parameter space and fit experimental data, followed by analysis of how the various factors (signaling network connectivity map, individual reaction kinetics, diffusion constraints, shape, etc.) affect the dynamics of spatial domains. The predictions generated from these simulations are then being tested experimentally in an iterative cycle of model building/refinement  simulation predictions  experiment.