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Modeling the Eukaryotic Cell Cycle Dynamics with Computational Biology

Explore the intricate molecular mechanisms and mathematical models governing the eukaryotic cell cycle. Learn about DNA replication, mRNA translation, protein synthesis, and cell division checkpoints. Use computational tools to simulate and analyze cell cycle progression.

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Modeling the Eukaryotic Cell Cycle Dynamics with Computational Biology

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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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