The document discusses the goals and challenges of the OpenWorm project, which aims to create a complete multi-scale simulation of the roundworm C. elegans. The simulation would model the worm at various levels, from individual cells and neurons to its whole body and environment. The goals are to better understand the worm and extract general design principles from biological systems that could be applied to modeling the human body. Key challenges include integrating models of the worm's genome, cells, tissues, nervous system, behavior and environment across multiple scales of size and time.

2. What I cannot create I do not understand Richard Feynman’s last board

3. 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

4. Reverse-engineering? A system whose mechanisms are obscured

5. What is reverse-engineering? System whose mechanisms are obscured Individual components and an explanation of how they fit together

6. What is reverse-engineering? Provide a framework of parts ready to be snapped together

7. Put the parts back together

8. A multi-scale synthesis problem

10. Enter the worm: c. elegans What’s up, baby?

11. Virtual physical organisms in a computer simulation

13. Enter the worm: c. elegans I’ve only got 1000 cells in my whole body… please simulate me!

14. A complete simulation of the worm’s brain, body and environment Simulated World Detailed simulation of worm body Detailed simulation of cellular activity

15. 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.

18. C. Elegans disease models Kaletta & Hengartner, 2006

19. Can present drugs Kaletta & Hengartner, 2006

20. Entire cell lineage mapped

21. Entire cell lineage mapped

22. Entire cell lineage mapped

23. Entire cell lineage mapped

24. Full connectome Varshney, Chen, Paniaqua, Hall and Chklovskii, 2011

25. P. Sauvage et al. / Journal of Biomechanics 2011 Biomechanics

27. Interrogation of Behavior

28. Core platform: Open Worm project

29. One core hooks together multiple simulation engines addressing diverse biological behavior

31. Mechanical model Palayanov, Khayrulin, Dibert (submitted)

32. 3D body plan Christian Grove, Wormbase

33. Team – A brief history

34. Collaboration technologies used

35. Jan – Sept 2011

36. Architecture

37. Neuronal model GPU Performance Testing: 302 Hodgkin-Huxley neurons for 140 ms (dt = 0.01ms) Architecture proof of concept using Hodgkin-Huxley neurons ms

38. Worm Browser http://www.youtube.com/watch?v=nAd9rMey- _0

39. Physics: SPH Smoothed particle hydrodynamics (SPH) algorithm for soft-body / liquid finite element interactions

40. Soft-body & fluid mechanics

41. Finite element modeling

42. C.elegans neuron models in NeuroML

43. Mendeley group has 234 references

44. Presented poster at Neuroinformatics 2011

48. Muscle cell with “arms” Cell Body 5 arms, 10 compartments each, passive currents Cell body, 1 compartment, active currents Boyle & Cohen, 2007

49. Case study: locomotion Gao et al, 2011

50. Conductance model of c. elegans muscle cell Boyle & Cohen, 2007

51. 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

52. Genetic Algorithms and Parameter optimization Achard, De Schutter, 2006

53. Gaming and crowdfunding