NRCAM Scientific Advisory Board 1/25/2010 9:15Coffee, donutsAll 9:30Introduction and OverviewLoew 9:45Demo of New Virtual Cell Features Loew, Moraru, Schaff, Cowan 11:00TR&D Progress and Plans 1.Biophysical Mechanisms Carson, Rodionov, Brown 11:302. Numerical ToolsSlepchenko 11:453. Enabling TechnologiesSchaff 12:004. Application DevelopmentMoraru 12:15Lunch 12:45Dissemination, TrainingCowan, Holmes 1:00CollaborationsLoew, Slepchenko, Ruebenacker 1:30Breakout Sessions Biology (Jacobson, Lederer, Pollard) E5036 Math/Physics/Comp (Greengard, MacLeod, Tyson, Colella(remote)) L5095 Carson, Cowan, Loew, Rodionov, Holmes, et al. Slepchenko, Schaff, Moraru, Resasco, et al. 3:00Advisors Executive Session L5095 Report writing Advisors 4:45Read back of report, open discussion L5095All 5:30Dinner L5095

The Team Les Loew – Co-PI; Biophysical Mechanisms Boris Slepchenko – Co-PI, Numerical Tools and Algorithms Jim Schaff – Co-PI, Software Development Leader Ion Moraru – Co-PI, System Administrator/Architect Ann Cowan – Co-PI, Dissemination, Service, Training *Michael Blinov – Rule-based modeling *Sofya Borinskaya – Graduate Student * Sherry-Ann Brown – Graduate Student John Carson – Co-I, Biophysical Mechanisms Yung-Sze Choi – Co-I, Mathematics *Jonathon Ditlev – Graduate Student *Jeff Dutton – System Manager and Support Fei Gao – Software Developer *Raquell Homes – Training, Dissemination *Pavel Kraykivskiy – Discrete models of cytoskeleton Susan Krueger – Website Developer, User facility *Anu Lakshminarayana – Software Developer Debbie Manchak - Administrative support ( funded through Institutional support) Frank Morgan – Software Developer *Igor Novak – Force-dependent integrin clustering, lateral diffusion, actin dynamics Diana Resasco – Numerics Vladimir Rodionov – Co-I, Biophysical Mechanisms *Oliver Ruebenacker – Software developer Irina Semenova – Organelle Trafficking *Dan Vasilescu - Software developer *Charles Wolgemuth – Moving boundaries *Li Ye – Software Developer Karen Zucker – Program Coordinator (funded through Institutional support) (*supported via collaborative grants)

Virtual Cell Capabilities Reaction - Diffusion - Advection - Electrophysiology 0, 1, 2 or 3 D including geometries from microscope images Stochastic simulators and Parameter Estimation for 0D Database of models and model components Biological Problems –Signaling and metabolic pathways –Intracellular trafficking –Ion channels –Fluorescent indicators and probe redistribution

The Big TR&D Picture Cell Biology Biophysical Mechanisms Numerical Tools Enabling Technologies Application Development DeveloperCommunity Prototype Code MathModel Workspace BioModel Workspace Standalone Application Drivers: Workflow: Products:

Biophysical Mechanisms 1.Macromolecular Aggregation - FCS studies of RNA delivery and translation in dendritic spines 2.Cytoskeletal dynamics – discrete spatial model of microtubule dynamics 3. Spatial electrophysiology – Computational methods for combined electrophysiological and biochemical modeling of neurons

Numerical Tools 1.Implementation of stiff PDE solvers in VCell – New fully implicit solver has been tested and deployed. 2.Implementation of elliptic solvers – Using VCell Poisson solver in the study of diffusion in crowded spaces 3. Adaptive meshes and parallelization – Major effort on adapting CHOMBO as a new solver for VCell

Enabling Technologies 1.Prototype implementation of moving boundaries 2.Progress in plugin architecture permits application of Smoldyn spatial stochastic simulator to VCell BioModel 3.Relaxed topology constraints for cell-cell communication and electrophysiology modeling.

Application Development 1.New software process – No news after last year’s full conversion to Eclipse 2.New server components – Full deployment of OSG cluster; standalone solvers 3. New user-level functionality – The Biomodel GUI has been expanded with much more flexible methods for model formulation and simulation specification 4. New VCell applications and deployment – Separate VFRAP application is the first rollout of specialized apps.

Impact Impact Feb ‘09 – Jan ‘10 Feb-09 Total Registered VCell Users – 12,364 Users Who Ran Simulations – 2,224 Currently Stored Models – 29,117 Currently Stored Simulations – 160,539 Publicly Available Models – 687 Publicly Available Simulations - 2,377 Jan-10 → 13,249 → 2,526 → 34,402 → 183,339 → 720 → 2,778

News New Deployed VCell Features (Demos) –Fully-Implicit Finite Volume Solver –Expressions for Advection and Diffusion in Biomodel –Geometries: segmentation support; analytical primitives –Generalized metadata and annotation support –GUI Improvements (auto complete; math description search and syntax highlight; SPPR; global functions for sims; detailed solver descriptions…) –VFRAP TCNP Grant will end this summer –no-cost extension for 1 additional year Systems Biology Grant Submitted SIG Grant for new cluster to be funded CSHL CCB Symposium 3/24-27/09; in Hinxton 2/10-14/10 CSHL CCB course 6/25 – 7/16, 2009; again this coming summer, 7/2-22/10

NIGMS Systems Biology Grant Physics of Cellular Systems A computational framework for spatial stochastic modeling of crowded molecular environments A computational framework for coarse grain modeling of molecular complexes A computational framework for modeling sub-cellular stresses and strains A computational infrastructure for integrating multiple physical formulations of biological systems A data-driven model of dendritic spine morphogenesis A data-driven model of cell adhesion morphology and cytoskeletal interactions A data-driven model of actin comet tail-driven propulsion A data-driven model of cell migration in the developing C. elegans embryo A UCONN Ph.D. training program in Cell Analysis and Modeling Educational programs especially inclusive of traditionally underrepresented populations Adoption of new physics-based analysis by the systems biology and cell biology research communities

Cell And Genome Sciences Building