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What I cannot create I do not understand Richard Feynman’s last board
A multi-scale data problem Scale Whole brain data (20 um microscopic MRI) Mosiac LM images (1 GB+) Conventional LM images Individual cell morphologies EM volumes & reconstructions Solved molecular structures
Reverse-engineering? A system whose mechanisms are obscured
What is reverse-engineering? System whose mechanisms  are obscured Individual components and an explanation of how they fit together
What is reverse-engineering? Provide a framework of parts ready to be snapped together
Put the parts back together
A multi-scale synthesis problem
Simulation-based research ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Enter the worm: c. elegans What’s up, baby?
Virtual physical organisms in a computer simulation
In search of nature’s design principles via simulation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Enter the worm: c. elegans I’ve only got 1000 cells in my whole body… please simulate me!
A complete simulation of the worm’s brain, body and environment Simulated World Detailed simulation of  worm body Detailed simulation of  cellular activity
The goal:  understanding  a faithfully simulated organism end to end Extracting mathematical principles from biological systems is necessary if we are going to understand and reconstruct the much larger system of the human.
Outreach: put the model online and let the world play with it ,[object Object],[object Object],[object Object]
Worm biology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
C. Elegans disease models Kaletta & Hengartner, 2006
Can present drugs Kaletta & Hengartner, 2006
Entire cell lineage mapped
Entire cell lineage mapped
Entire cell lineage mapped
Entire cell lineage mapped
Full connectome Varshney, Chen, Paniaqua, Hall and Chklovskii, 2011
P. Sauvage et al. / Journal of Biomechanics 2011 Biomechanics
 
Interrogation of Behavior
Core platform: Open Worm project
One core hooks together multiple simulation engines addressing diverse biological behavior
Estimates of computational complexity ,[object Object],[object Object],[object Object],[object Object],[object Object],Source:  http://csgillespie.wordpress.com/2011/01/25/cpu-and-gpu-trends-over-time/
Mechanical model Palayanov, Khayrulin, Dibert (submitted)
3D body plan Christian Grove, Wormbase
Team – A brief history
Collaboration technologies used
Jan – Sept 2011
Architecture
Neuronal model GPU Performance Testing:  302 Hodgkin-Huxley neurons for 140 ms (dt = 0.01ms) Architecture proof of concept using Hodgkin-Huxley neurons ms
Worm Browser http://www.youtube.com/watch?v=nAd9rMey- _0
Physics: SPH Smoothed particle hydrodynamics (SPH) algorithm for soft-body / liquid finite element interactions
Soft-body & fluid mechanics
Finite element modeling
C.elegans neuron models in NeuroML
Mendeley group has 234 references
Presented poster at Neuroinformatics 2011
OpenWorm links: ,[object Object],[object Object],[object Object]
[object Object]
 
Muscle cell with “arms” Cell Body 5 arms,  10 compartments each, passive currents Cell body, 1 compartment, active currents Boyle & Cohen, 2007
Case study: locomotion Gao et al, 2011
Conductance model of c. elegans muscle cell Boyle & Cohen, 2007
Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Cell Body Quadrant 1 Quadrant 2 Quadrants of muscle cells
Genetic Algorithms and Parameter optimization Achard, De Schutter, 2006
Gaming and crowdfunding

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Richard Feynman’s Last Board