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The Eukaryotic Cell Cycle : Molecules, Mechanisms, and Mathematical Models

The Eukaryotic Cell Cycle : Molecules, Mechanisms, and Mathematical Models. John J. Tyson Virginia Tech Bela Novak Tech Univ Budapest. DNA. …TACCCGATGGCGAAATGC. mRNA. …AUGGGCUACCGCUUUACG. …Met -Gly -Tyr -Arg -Phe -Thr. Protein. -P. Enzyme. ATP. ADP. E 4. E 1. E 3.

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The Eukaryotic Cell Cycle : Molecules, Mechanisms, and Mathematical Models

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  1. The Eukaryotic Cell Cycle :Molecules, Mechanisms, and Mathematical Models John J. Tyson Virginia Tech Bela Novak Tech Univ Budapest

  2. DNA …TACCCGATGGCGAAATGC... mRNA …AUGGGCUACCGCUUUACG... …Met -Gly -Tyr -Arg -Phe -Thr... Protein -P Enzyme ATP ADP E4 E1 E3 Reaction Network X Y Z E2 Cell Physiology Computational Molecular Biology

  3. G1 cell division S M (telophase) G2 M (anaphase) M (metaphase)

  4. G1 Checkpoint Sic1 Cln2 Cdh1 Clb5 Cdk1 Cdc20 Clb2 G2 Checkpoint Metaphase Checkpoint G1 cell division Start S M (telophase) G2 M (anaphase) Finish M (metaphase)

  5. Sister chromatid separation Unaligned Xsomes Cdh1 Clb5 Clb2 Cdc20 Cdc20 Mcm1 Clb2 Sic1 Mitosis Clb2 Clb2 Cdc20 Sic1 Sic1 Swi5 P Sic1 Cln2 Clb5 Clb? Budding Cln2 SBF Mass Cdh1 Cln3 and Bck2 SCF Cdc20 MBF Clb5 DNA synthesis

  6. synthesis synthesis binding degradation degradation activation inactivation

  7. G1 S/M Simulation of the budding yeast cell cycle mass Sic1 Cln2 Clb2 Cdh1 Cdc20 Time (min)

  8. Cdk Cln CKI CKI = Sic1 CKI +APC Cdh1 +APC Cdk Cdc20 Cln Cdk CycB

  9. Why do these calculations? Is the model “yeast shaped”? Bioinformatics role: the model organizes lots of experimental information. New science: prediction, insight

  10. Cdc20 Cdk1 Clb2,5 Cdk1 activity M period Sic1 Cdh1 G1 Cln2 mass

  11. Cdc20 Bifurcation diagram Cdk1 Clb2,5 Cdk1 activity M Sic1 Cdh1 G1 Cln2 cell mass

  12. How can CS help? Experimental Database Wiring Diagram Differential Equations Parameter Values Simulation Analysis Visualization-Translation Experimental Database

  13. Problem-Solving Environment Cliff Shaffer Naren Ramakrishnan Marc Vass Layne Watson Jason Zwolak

  14. Simulation Translation Database Prop 1 Good fit Prop 1 Prop 2 Bad fit Prop 2 ... ... ... Error Function (parameters) Parameter Estimation

  15. Parameter Estimation

  16. Kurt Kohn (1999) Mol Biol Cell

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