Modeling the Growing Plant: The Arabidopsis Shoot Apical Meristem

1. Modeling the Growing Plant: The Arabidopsis Shoot Apical Meristem Bruce E. Shapiro Biological Network Modeling Center The Beckman Institute at Caltech bshapiro@caltech.edu www.computableplant.org

2. Some Background Information • Fluorescent Probe Confocal Microscopy • Arabidopsis • Connectivity & Cell Walls form Delaunay and Voronoi • Cell Division and Plant Growth • Phyllotaxis • Cell Differentiation

3. http://www.computableplant.org • National Science Foundation (US) Frontiers in Integrative Biological Research (FIBR) Program Grants (First grants: Sept. 2003) • must integrate research tools from across multiple disciplines: biology, math, physical sciences, information technology • not limited by organizational boundaries • must answer a fundamental biological question • 5 year duration, renewable, ≈$1,000,000/year • 5± new grants annually

4. "To analyze the charms of flowers is like dissecting music; it is one of those things which it is far better to enjoy than to attempt to understand.” [Henry Tuckerman, 1853] • “The project will track cell-by-cell changes in the mustard plant's meristem - the tissue in which cells actively divide and then differentiate into specialized cells. With fluorescent proteins marking specific cell types in specially designed transgenic plants, researchers will be able to trace the development of leaves and flowers.” [NSF Press Release, 2003]

5. Eric Mjolsness (PI) Pierre Baldi Alex Sadovsky Tigran Bacarian Alexi Vorbyov Ashish Bhan Fang Fang Elliot Meyerowitz Marcus Heisler Venu Reddy Adrienne Roeder Vikas Agrawal* Bruce Shapiro Victoria Gor Nikolai Kolchanov Nadya Omelianchuk Nikolay Podkolodny Sergei Nikolaev Vitali Likhoshvai Henrik Jönsson US National Science Foundation FIBR Grant 0330786

6. ... to bring together Caltech biologists, bioengineers, mathematicians, and computer scientists to develop and apply state-of-the-art computational tools for modeling and analyzing complex biological systems.

7. Mjolsness E. Stochastic Process Semantics for Dynamical Grammer Syntax: An Overview. 9th International Symposium on Artificial Intelligence and Mathematics, Jan 2006. Reddy GV, Meyerowitz EM. Stem-Cell Homeostasis Growth Dynamics can be Uncoupled in the Arabidopsis Shoot Apex. Science 310(5748):663-667.

8. Systems Biology Ontology

9. Fluorescent Probe Confocal Microscopy • Arabidopsis • Connectivity & Cell Walls form Delaunay and Voronoi • Cell Division and Plant Growth • Phyllotaxis • Cell Differentiation

10. lifesci.ucsb.edu/~biolum www.reefs.org Luminescent Jellyfish Aequoria victoria

11. Marc Zimmer (Photo: Osamu Shimomura) http://www.conncoll.edu/ccacad/zimmer/GFP-ww/GFP2.htm Luminescent Jellyfish Aequoria victoria

12. Marc Zimmer GFP: Green Fluorescent Protein

13. Commercial Markers www.anticancer.com Neurons J. Lichtman,Science (2003) Transgenic Art Eduardo Kac Nikon’s Microscopyu.com GFP: Green Fluorescent Protein

14. Fluorescence Microscopy Higher Energy State Internal Energy Loss Intermediate State Sample absorbs high energy photon from laser Photon Emitted Ground State

16. Laser Scanning Confocal MicroscopeZeiss LSM-510 Venu Reddy Marcus Heisler

17. Fluorescent Probe Confocal Microscopy • Arabidopsis • Connectivity & Cell Walls form Delaunay and Voronoi • Cell Division and Plant Growth • Phyllotaxis • Cell Differentiation

18. Shoot Apical Meristem

19. Geographical distribution of Arabidopsis thaliana. Koornneff, Ann. Rev. Plant Biol. 2004

20. Cell 88:299-308 (1997) Live Imaging

21. 51 image “z-stack”

22. PIN1:GFP (blue),REVOLUTA:YFP (green)andpFIL:dsRED (red) Marcus Heisler, Caltech

23. Cell 88:299-308 (1997) Tracing Cell Lineages Development 131:4225 (2004) Reddy et al

24. Venu Reddy, Caltech

25. Cell centers: Gradient Descent

26. Tracking cell motion Thin Plate Splines Softassign

27. Stress Tensor

28. WallsExtracted by Watershed/Voronoi Model PIN1

29. Auxin Derived from PIN1 pH=5.0 pH=4.5 pH=5.5

30. Fluorescent Probe Confocal Microscopy • Arabidopsis • Connectivity & Cell Walls form Delaunay and Voronoi • Cell Division and Plant Growth • Phyllotaxis • Cell Differentiation

31. Cell Walls: Voronoi Model

32. Cell Connectivity: Delaunay

33. Raw Data - (x, y, z) cell “centers”

39. 3D modified Voronoi Cross-section

40. Slabs Flattened to 2D, modified Voronoi

42. DiscreteMath`ComputationalGeometry`DelaunayTriangulation qdelaunay regtet

43. Fluorescent Probe Confocal Microscopy • Arabidopsis • Connectivity & Cell Walls form Delaunay and Voronoi • Cell Division and Plant Growth • Phyllotaxis • Cell Differentiation

44. Shoot Apical Meristem - tip of plant Central Zone: Provides new cells Flower bud Peripheral Zone: Leaves, Flower Formation MERISTEM Rib:Cells divide and “push” Meristem up STEM 50 scale bar

45. Protein regulation model Internal External Receptor, c - Ligand, b Mjolsness, Sharp & Reinitz J. Theor. Biol. 152: 429 (1991) Shapiro, Levchenko, Mjolsness, Meyerowitz, Wold, Bioinformatics19(5):677 (2003)

46. Growth Model • Constant growth rate: • Cell division on mass threshold • Viscous spring model:

47. Meristem Maintenance and Growth Mjolsness, Shapiro, Jönnson & Meyerowitz in BGRS, Kluwer (2002); also EMBS (2002)

48. Fluorescent Probe Confocal Microscopy • Arabidopsis • Connectivity & Cell Walls form Delaunay and Voronoi • Cell Division and Plant Growth • Phyllotaxis • Cell Differentiation

49. Phyllotaxis

50. Auxin - A Plant Hormone Indole-3-acetic acid Synthesized from tryptophan?