Measure

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The Center for Cell Analysis and Modeling focuses
on creating new technologies for understanding
the dynamic distributions of molecules in living
cells. Three Technology Development projects
integrate multidisciplinary approaches to
Measure, Model and Manipulate intracellular
events.
Measure
Model
Model
Manipulate
Developing tools to address a fundamental problem
of cell function how signaling networks
regulate, and are regulated by, the spatial
organization of molecules in cells
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Random walk in crowded spaces
Orthogonal cylindrical lattice
Randomly placed cylinders
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gfit - software for global analysis of experiments
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VCell actin polymerization and branching model
L. Loew, N. Vacanti, J. Ditlev
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Virtual Cell Usage Sept 06 Total
Registered VCell Users 9,644 Users Who Ran
Simulations 1,277 Currently Stored Models
17,295 Currently Stored Simulations
30,559 Publicly Available Models
343 Publicly Available Simulations - 710
Feb 08 ? 11,082 ? 1,737 ?
23,805 ? 112,974 ? 531 ? 1,887
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The Problem
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Quantitative Cell Biology

• 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?

Experiment
Predictions Dynamics of Cellular Structures and
Molecules
Simulation
Trends in Cell Biology 13570-576 (2003)
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Distributed Architecture
Compute Cluster
Physiology Editor
Geometry Editor
Application Editor
Document Manager
Database (Oracle)
Database Service
Database Service
Database Service
Connection Manager
Data Export Service
Data Export Service
Data Export Service
Storage Cluster
Siumulation Data Service
Siumulation Data Service
Siumulation Data Service
JMS Broker (SonicMQ)
Simulation Dispatch Service
Simulation Dispatch Service
Simulation Dispatch Service
Simulation Editor Simulation Monitor
Simulation Worker Service
Simulation Worker Service
Simulation Worker Service
Batch Scheduler (PBSPro)
Simulation Data
Compiled Simulation Jobs
Compiled Simulation Jobs
Compiled Simulation Jobs
Compiled Simulation Jobs
Compiled Simulation Jobs
Compiled Simulation Jobs
Data Viewer Data Exporter
Compiled Simulation Jobs
Server Manager
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single modellocations/molecules/mechanisms
non-spatial appsODEs, sensitivity
analysismultiple simulations
spatial apps1D,2D,3D PDEsreaction/diffusion/adve
ctionmultiple simulations
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Math Models
non-spatial Math ModelODEs, sensitivity
analysismultiple simulations
spatial Math Model1D,2D,3D PDEsreaction/diffus
ion/advectionmultiple simulations
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Minimal Usage Requirements

• Registration
• Free separate link on website
• Java
• Version 1.5 or later (except Mac 1.4 required)
• Runs as installed application or as web applet
• Internet connection (for full functionality)
• Required for
• Database access
• Running simulations
• Viewing results
• Fast without firewalls! but will use
  tunneling
• A large monitor !

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Typical usage

• Define physiology
• Create compartments
• Add species
• Add reactions/fluxes
• Create an application
• Choose and map geometry (try compartmental
  first!!)
• Specify initial conditions
• Create a simulation
• Choose resolution
• Choose numerical conditions (timestep!!)
• Run simulation
• View results
• Export and analyze data
• Create new simulations
• Create new applications
• Create new BioModels

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Math and Physics
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Current Scope and Future Plans

• Intended Users
• Biologists
• Biophysicists/Mathematicians
• Modeling domain
• Compartmental or 1D, 2D, 3D Geometry
• Reaction/Diffusion/Membrane Transport
• Electric Potential (electrophysiology)
• Advection Directed Transport
• Membrane Diffusion
• Optimization parameter scans
• Under development
• Stochastic Processes
• Complexes
• Protocols
• Constraints Virtual Experiments
• Stand-alone grid-based versions
• New architecture plug-ins, modules, etc. (VCell
  OpenSource)
• Cell motility

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Standards and Resources

• Languages and Ontologies
• SBML
• CellML
• VCell imports/exports SBML, CellML ?? VCML
• BioPAX
• SBO
• SBGN
• MIRIAM
• MIRIAM2, MIASE, KiSAO
• Repositories
• BioModels database
• JWS Online
• Database of Quantitative Cellular Signaling
• CellML model repository

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Combinatorial Complexityand Modularity 2
examples of external tools integration
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Solution 1 BioNetGen_at_VCell http//vcell.org/bi
onetgen
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Solution 2 BioPAX_at_VCell http//reactome.org
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Standalone VCell Applications

• Virtual FRAP tool
• Data-centric, predefined context
• First prototype standalone application
• Virtual Microscopy tool
• Model-centric, more flexible

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Leveraging CMU Resources

• What?
• Connect VCell to PSLID and SLIF
• Use generative models for virtual geometries
  and virtual molecular distributions
• Why?
• Provide a large source of public image-based
  geometries and quantitative data to VCell users
• Provide realistic artificial data to
  complement/supplant real data
• How?
• Search/import interface for CMU databases
• XML repository of generative models
• Server-side Matlab libraries
• Use field data for conversion

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The Virtual Cell Project

• Michael Blinov
• John Carson
• Yung-Sze Choi
• Ann Cowan
• Fei Gao
• Pavel Kraikiwski
• Susan Krueger
• Anu Lakshminarayana
• Michael Levin
• Frank Morgan
• Igor Novak
• Diana Resasco
• Li Ye
• Rashad Badrawi
• Jeff Dutton
• Daniel Lucio
• Dong-Guk Shin
• John Wagner

Les Loew Jim Schaff Ion Moraru Boris Slepchenko