NRCAM Scientific Advisory Board1/25/2010

9:15 Coffee, donuts All9:30 Introduction and Overview Loew9:45 Demo of New Virtual Cell Features  Loew, Moraru, Schaff ,

Cowan11:00 TR&D Progress and Plans

1.Biophysical Mechanisms Carson, Rodionov, Brown

11:30 2. Numerical Tools Slepchenko

11:45 3. Enabling Technologies Schaff

12:00 4. Application Development Moraru

12:15 Lunch  

12:45 Dissemination, Training Cowan, Holmes

1:00 Collaborations Loew, Slepchenko, Ruebenacker

1:30 Breakout SessionsBiology (Jacobson, Lederer, Pollard) E5036Math/Physics/Comp (Greengard, MacLeod, Tyson, Colella(remote)) L5095

Carson, Cowan, Loew, Rodionov, Holmes, et al.Slepchenko, Schaff, Moraru, Resasco, et al.

3:00 Advisors Executive Session L5095Report writing

Advisors

4:45 Read back of report, open discussion L5095 All5:30 Dinner L5095  

The TeamLes Loew – Co-PI; Biophysical MechanismsBoris Slepchenko – Co-PI, Numerical Tools and Algorithms Jim Schaff – Co-PI, Software Development Leader Ion Moraru – Co-PI, System Administrator/ArchitectAnn Cowan – Co-PI, Dissemination, Service, Training *Michael Blinov – Rule-based modeling *Sofya Borinskaya – Graduate Student * Sherry-Ann Brown – Graduate StudentJohn 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 dynamicsDiana Resasco – Numerics Vladimir Rodionov – Co-I, Biophysical Mechanisms *Oliver Ruebenacker – Software developerIrina 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

iii Rt

C Fdiv

The Big TR&D PictureThe Big TR&D Picture

Cell BiologyCell Biology

BiophysicalMechanisms

NumericalTools

EnablingTechnologies

ApplicationDevelopment

DeveloperDeveloperCommunityCommunity

PrototypeCode

MathModelWorkspace

BioModelWorkspace

StandaloneApplication

Drivers:Drivers:

WorkWorkflow:flow:

Products:Products:

Biophysical MechanismsBiophysical Mechanisms1. 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 ToolsNumerical 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 TechnologiesEnabling 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 DevelopmentApplication Development1. 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.

ImpactImpactFeb ‘09 – Jan ‘10

Feb-09

Total Registered VCell Users – 12,364Users Who Ran Simulations – 2,224Currently Stored Models – 29,117Currently Stored Simulations – 160,539Publicly Available Models – 687Publicly Available Simulations - 2,377

Jan-10

→ 13,249→ 2,526→ 34,402→ 183,339→ 720 → 2,778

NewsNews

• 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 GrantPhysics 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

Cell And Genome Sciences Building