This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
| Ron, Amit; Azeloglu, Evren U; Calizo, Rhodora C et al. (2017) Cell shape information is transduced through tension-independent mechanisms. Nat Commun 8:2145 |
| Schaff, James C; Gao, Fei; Li, Ye et al. (2016) Numerical Approach to Spatial Deterministic-Stochastic Models Arising in Cell Biology. PLoS Comput Biol 12:e1005236 |
| Semenova, Irina; Ikeda, Kazuho; Resaul, Karim et al. (2014) Regulation of microtubule-based transport by MAP4. Mol Biol Cell 25:3119-32 |
| Novak, Igor L; Slepchenko, Boris M (2014) A conservative algorithm for parabolic problems in domains with moving boundaries. J Comput Phys 270:203-213 |
| Michalski, Paul J (2014) First demonstration of bistability in CaMKII, a memory-related kinase. Biophys J 106:1233-5 |
| Azeloglu, Evren U; Hardy, Simon V; Eungdamrong, Narat John et al. (2014) Interconnected network motifs control podocyte morphology and kidney function. Sci Signal 7:ra12 |
| Falkenberg, Cibele Vieira; Loew, Leslie M (2013) Computational analysis of Rho GTPase cycling. PLoS Comput Biol 9:e1002831 |
| Dickson, Eamonn J; Falkenburger, Björn H; Hille, Bertil (2013) Quantitative properties and receptor reserve of the IP(3) and calcium branch of G(q)-coupled receptor signaling. J Gen Physiol 141:521-35 |
| Michalski, P J (2013) The delicate bistability of CaMKII. Biophys J 105:794-806 |
| Falkenburger, Björn H; Dickson, Eamonn J; Hille, Bertil (2013) Quantitative properties and receptor reserve of the DAG and PKC branch of G(q)-coupled receptor signaling. J Gen Physiol 141:537-55 |
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