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How Do Cells Compute?

How Do Cells Compute?. John J. Tyson Department of Biological Sciences Virginia Bioinformatics Institute. Do Cells Compute?. 00. 0. 01. 1. either A or B but not both. 10. 1. 11. 0. Computer. bit string. bit string. N N 2. computations.

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How Do Cells Compute?

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  1. How Do Cells Compute? John J. Tyson Department of Biological Sciences Virginia Bioinformatics Institute

  2. Do Cells Compute?

  3. 00 0 01 1 either A or B but not both 10 1 11 0 Computer bit string bit string N N2 computations x decisions

  4. Is the cell anInformation Processing System? IPS input output

  5. nutrients growth & division repellants movement hormones gene expression damage death heat shock Cell

  6. Glucose glucose metabolizing enzymes 1 Lactose Bacteria 1 lactose metabolizing enzymes 0 0

  7. Glucose glucose metabolizing enzymes 1 Lactose Bacteria 1 lactose metabolizing enzymes 1 0

  8. Glucose glucose metabolizing enzymes 1 Lactose Bacteria 0 lactose metabolizing enzymes 1 1

  9. Glucose glucose metabolizing enzymes 1 Lactose Bacteria 0 lactose metabolizing enzymes 0 0

  10. Fission Yeast 7 mm 14 mm Wild type Mutant (wee1D) different “set point” “size control”

  11. Fibroblast cell cycle arrest repair Ionizing radiation damages DNA

  12. Fibroblast Programmed Cell Death

  13. Silicon Silicon Carbon Carbon Solid state Watery Digital Analog Sequential Parallel Programmable Hard-wired Precise Sloppy Manufactured Self-reproducing DGaD Designed LoDD Evolved Is a cell like a computer? Laptop Cell

  14. …in the last 5 years Cell Carbon Carbon “Molecular Systems Biology” Watery Analog Parallel Hard-wired Sloppy Self-reproducing Evolved

  15. 20 years ago… Cell Winfree & Kauffman Oster & Perelson Goldbeter & Segel Glass & Mackey Rinzel & Keizer Goodwin, Meinhardt, Odell, Tyson, … Carbon Carbon Watery Analog Parallel Hard-wired Sloppy Self-reproducing Evolved

  16. WT cdc wee How do cells make decisions? Paul Nurse, Nature (1975)

  17. WT cdc wee MPF Mitosis Promoting Factor + + Fission Yeast Wee1 P Wee1 CycB P Cdc25 P CycB cdc25ts wee1OP Cdc25 wee1ts cdc25OP

  18. M S/G2 wee1D wee1OP SN 14mm + + Fission Yeast Mitosis & Cell Division Wee1 P MPF Wee1 CycB P DNA synthesis Cdc25 P CycB size Cdc25 size

  19. Size at Division1.0 = WT size wee1OP cdc cdc25OP cdc25ts WT Wee1 activity (%) wee cut quantized wee1ts Cdc25 activity (%)

  20. Wee1 MPF total cyclin P Cdc20 ks Wee1 CycB P APC-P APC Cdc25 P Cdc20 CycB MPF Cdc25

  21. total cyclin MPF Cell(2005) Joe Pomerening

  22. M S/G2 MPF MPF ks size How do cells compute? Switches and Clocks

  23. The class of chemical switching networks will be promising candidates for a possible new technology of chemical reaction systems.

  24. The living cell is Rössler’s“flüssiges Automata”:a miniature, self-reproducing, water-soluble biochemical computer. nutrients growth & division repellants movement hormones gene expression damage death heat shock

  25. $$: DARPA, NIH, McDonnell Foundation

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