The National Resource for Cell Analysis and Modeling (NRCAM) develops new technologies for modeling cell biological processes. The technologies are integrated through Virtual Cell (VCell), a problem solving environment built on a central database and disseminated as a web application. The philosophy of VCell centers on model reuse, where a physiological model can be repeatedly interrogated and altered to address new hypotheses. For example, a given physiology can be simulated with 4 different methods, including deterministic or stochastic with either compartmental or explicit geometric representations (including experimental images). The VCell model building interface contains abstractions to explicitly support key biophysical mechanisms, including reaction kinetics, diffusion, flow, membrane transport, lateral membrane diffusion and electrophysiology. The technology research is divided into 4 projects. Biophysical Mechanisms will develop equations to address mechanisms not fully supported by the current VCell software: electrophysiology in neuronal geometries, cytoskeletal dynamics, mechanics and the combinatorial complexity of multi-molecular complexes. Numerical Algorithms will develop a new solver for systems with disparate spatial scales, a hybrid deterministic-stochastic spatial simulator, methods for spatially non-uniform electric potentials and a tool to simulate cells with moving boundaries. Data Driven Modeling proposes to significantly enhance VCell support for experimental data to both facilitate analysis of experimental data through tools like Virtual FRAP, and to permit direct comparison of simulation and experiment through parameter estimation and visualization technologies. The overall goal of the project on Model Building Blocks is to enhance VCell with features to aid in the model construction process;these include new software abstractions, links to external databases, rule-based modeling and maintaining support for community standards. A diverse group of 8 Driving Biological Projects and 10 collaborative projects from outstanding scientists are described. Through a rich repertoire of training, dissemination and outreach activities, NRCAM promotes a quantitative approach to cell biological research.
Computational modeling, enabled by the newly proposed VCell technologies and the supported collaborations, will offer deep insights into the cellular basis of disease, especially as related to the cardiac, nervous and immune systems and cancer. It will also enable computational modeling of pharmacological interventions.
Jadwin, Joshua A; Curran, Timothy G; Lafontaine, Adam T et al. (2018) Src homology 2 domains enhance tyrosine phosphorylation in vivo by protecting binding sites in their target proteins from dephosphorylation. J Biol Chem 293:623-637 |
Erdemir, Ahmet; Hunter, Peter J; Holzapfel, Gerhard A et al. (2018) Perspectives on Sharing Models and Related Resources in Computational Biomechanics Research. J Biomech Eng 140: |
Falkenberg, Cibele V; Azeloglu, Evren U; Stothers, Mark et al. (2017) Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability. PLoS Comput Biol 13:e1005433 |
Mohan, Krithika; Nosbisch, Jamie L; Elston, Timothy C et al. (2017) A Reaction-Diffusion Model Explains Amplification of the PLC/PKC Pathway in Fibroblast Chemotaxis. Biophys J 113:185-194 |
Blinov, Michael L; Schaff, James C; Vasilescu, Dan et al. (2017) Compartmental and Spatial Rule-Based Modeling with Virtual Cell. Biophys J 113:1365-1372 |
Nickaeen, Masoud; Novak, Igor L; Pulford, Stephanie et al. (2017) A free-boundary model of a motile cell explains turning behavior. PLoS Comput Biol 13:e1005862 |
Jung, Seung-Ryoung; Kushmerick, Christopher; Seo, Jong Bae et al. (2017) Muscarinic receptor regulates extracellular signal regulated kinase by two modes of arrestin binding. Proc Natl Acad Sci U S A 114:E5579-E5588 |
Falkenberg, Cibele Vieira; Carson, John H; Blinov, Michael L (2017) Multivalent Molecules as Modulators of RNA Granule Size and Composition. Biophys J 113:235-245 |
Marchenko, Olena O; Das, Sulagna; Yu, Ji et al. (2017) A minimal actomyosin-based model predicts the dynamics of filopodia on neuronal dendrites. Mol Biol Cell 28:1021-1033 |
Borinskaya, Sofya; Velle, Katrina B; Campellone, Kenneth G et al. (2016) Integration of linear and dendritic actin nucleation in Nck-induced actin comets. Mol Biol Cell 27:247-59 |
Showing the most recent 10 out of 51 publications