the problem. the virtual cell project rashad badrawi john carson yung-sze choi ann cowan fei gao...
TRANSCRIPT
The ProblemThe Problem
The Virtual Cell Project Rashad Badrawi John Carson Yung-Sze Choi Ann Cowan Fei Gao Susan Krueger Anu Lakshminarayana Daniel Lucio Frank Morgan Igor Novak Diana Resasco Dong-Guk Shin John Wagner
NIGMS NSF
Ion Moraru Jim Schaff Boris Slepchenko
Quantitative Cell BiologyQuantitative Cell Biology
Predictions
Dynamics of Cellular Structures and
Molecules
Simulation
Hypothesis (Model)
•What are the initial concentrations, diffusion coefficients and locations of all the implicated molecules?
•What are the rate laws and rate constants for all the biochemical transformations?
•What are the membrane fluxes and how are they regulated?
•How are the forces controlling cytoskeletal mechanics regulated?
ExperimentExperiment
Trends in Cell Biology 13:570-576 (2003)
The Virtual Cell – Modeling Reactions and Diffusion
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Applications
Topology Geometry,
Initial Conditions, Boundary Conditions, Diffusion Coefficients,
Pseudo-steady, Enable/Disable Reactions
Images
Applications
Topology Geometry,
Initial Conditions, Boundary Conditions, Diffusion Coefficients,
Pseudo-steady, Enable/Disable Reactions
Images
Applications
Topology Geometry,
Initial Conditions, Boundary Conditions, Diffusion Coefficients,
Pseudo-steady, Enable/Disable Reactions
Images
Applications
Topology Geometry,
Initial Conditions, Boundary Conditions, Diffusion
Coefficients, Pseudo-steady, Enable/Disable Reactions
Electrophysiology Protocols
Images
Math DescriptionMath DescriptionMath Description
VCMDL
Simulations
Timestep,Mesh Size,ParameterSearches,Sensitivity Results
Simulations
Timestep,Mesh Size,ParameterSearches,Sensitivity Results
Simulations
Timestep,Mesh Size,ParameterSearches,Sensitivity Results
Simulations
Timestep,Mesh Size,ParameterSearches,Sensitivity Results
Physiology
Molecular SpeciesCompartment Topology
Reactions and Fluxes
VCDB
Bradykinin Induced Calcium Wave in a Neuroblastoma Cell
Experiment
Simulation
C. Fink et al., JCB, 1999C. Fink et al., BJ, 2000
Other model examples
•Model of Stress-Dependent Focal Adhesion Dynamics: (Novak)•Modeling mpf activation at fertilization: stochastic modeling (Slepchenko and Terasaki)•Modeling active intracellular transport in sea urchin (advection) (Rodionov)•Intracellular trafficking of RNA granules (stochastic modeling) Carson•Diffusion Processes in Mitochondria (Moraru)•TIR FRAP experiment at ribbon synapses•Calcium wave at fertilization in Xenopus eggs (Nuccitelli)•Nuclear envelope breakdown at fertilization (Terasaki & Slepchenko)
http://vcell.orghttp://vcell.org
What we can't do yet – but are working on….
•Diffusion within the membrane•2D in final testing•3D coming next
•Stochasitc events/discrete particles (large scale)•In Math Interface, not in Biology Interface
•Changing geometries•Very hard, in deep development
•Input spatial changes in species concentrations directly from images.