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

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Presentation transcript:

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

Computational Molecular Biology DNA mRNA Protein Enzyme Reaction Network Cell Physiology …TACCCGATGGCGAAATGC... …AUGGGCUACCGCUUUACG... …Met -Gly -Tyr -Arg -Phe -Thr... ATP ADP -P XYZ E1E1 E2E2 E3E3 E4E4

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

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

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

synthesisdegradationsynthesis degradation binding activationinactivation

Time (min) Sic1 mass Clb2 Cln2 Cdh1 Simulation of the budding yeast cell cycle G1S/M Cdc20

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

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

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

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

How can CS help? Experimental Database Wiring Diagram Differential EquationsParameter Values Analysis Simulation Visualization-Translation Experimental Database

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

Parameter Estimation DatabaseSimulationTranslation Prop 1 Good fit Prop 2 Bad fit... Error Function (parameters)

Parameter Estimation

Kurt Kohn (1999) Mol Biol Cell

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