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New Frontiers in Systems Biology

New Frontiers in Systems Biology. John J. Tyson. Department of Biology and Virginia Bioinformatics Institute Virginia Polytechnic Institute and State University Blacksburg, Virginia. Systems Science.

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New Frontiers in Systems Biology

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  1. New Frontiers in Systems Biology John J. Tyson Department of Biology and Virginia Bioinformatics Institute Virginia Polytechnic Institute and State University Blacksburg, Virginia

  2. Systems Science …the use of mathematics to study how the parts of a complex system fit together to function in ways that transcend the properties of the individual parts.

  3. Systems Science is the flip-side of Reductionist Science. reductionist science (parts) systems science (whole) Norbert Weiner (1948) Cybernetics: Control & Communication in the Animal and the Machine

  4. Outline Weather Forecasting Traditional Systems Biology “New” Systems Biology

  5. The map is a snapshot of the highs and lows at one instant; weather is a dynamic process…the movement of air masses in time across the continent. Weather Forecasting

  6. Navier-Stokes Equations Modern weather prediction is based on accurate computer “simulations” of moving air masses. Weather Forecasting

  7. Weather Forecasting Accurate weather forecasting is essential to modern… Transportation industry Military planning Civil defense

  8. Biological Systems Ecosystems Odum, MacArthur, Wilson, May, … Infectious disease

  9. Biological Systems Ecosystems Organ systems Entelos: math model of human digestive system— diabetes, obesity

  10. Biological Systems Organ systems Ecosystems Animal cell “Systems-level” thinking has been slow to catch on because…

  11. … the “parts list” was missing 1985-2000: The era of reductionist molecular biology; discovery of the parts list (proteins and the genes that encode them); culminating in the complete sequence of the human genome.

  12. New Systems Biology …the use of mathematics to study how genes and proteins interact to produce the complex behaviors of a living cell… movement energy supply signaling growth division death

  13. External signals Growth Development Division Reproduction Death Information Processing System Cell signaling Hanahan & Weinberg (2000)

  14. Division Reproduction Cell signaling Hanahan & Weinberg (2000)

  15. The Budding Yeast Cell Cycle budding DNA synthesis growth mitosis newborn cell cell division

  16. Pds1 Esp1 Cdc14 RENT Sic1 Sic1 P Esp1 Cell division unaligned chromosomes SBF Cdh1 Pds1 Mcm1 Cdc20 PPX Net1P Tem1-GDP Cdc15/MEN Lte1 Bub2 Tem1-GTP Net1 Mcm1 Cdh1 Cdc20 Cln2 Clb2 Clb5 Mitosis Mad2 growth APC-P unaligned chromosomes Mcm1 Cdc20 Cdh1 Clb2 APC Inactive trimer Cdc14 and Cln3 Swi5 CDKs SCF P Cdc14 Bck2 Inactive trimer ? MBF Clb5 DNA synthesis Clb2 SBF Cln2 Budding

  17. Pds1 Esp1 Cdc14 RENT Sic1 Sic1 P Esp1 Cell division unaligned chromosomes SBF Cdh1 Pds1 Mcm1 Cdc20 PPX Net1P Tem1-GDP Cdc15/MEN Lte1 Bub2 Tem1-GTP Net1 Mcm1 Cdh1 Cdc20 Cln2 Clb2 Clb5 Mitosis Mad2 growth APC-P unaligned chromosomes Mcm1 Cdc20 Cdh1 Clb2 APC Inactive trimer Cdc14 and Cln3 Swi5 CDKs SCF P Cdc14 Bck2 Inactive trimer ? MBF Clb5 DNA synthesis Clb2 SBF Cln2 Budding

  18. synthesis synthesis binding degradation degradation inactivation activation The mathematical model

  19. G1 S/M mass CKI Cln2 Clb2 Cdh1 Cdc20 Time (min)

  20. 46,000 Full Details: http://mpf.biol.vt.edu

  21. Pds1 Esp1 Cdc14 RENT Sic1 Sic1 P Esp1 Sister chromatid separation unaligned chromosomes SBF Cdh1 Pds1 Mcm1 Cdc20 PPX Net1P Mutants Tem1-GDP Cdc15/MEN Lte1 Bub2 Tem1-GTP Net1 Mcm1 Cdh1 Cdc20 Cln2 Clb2 Clb5 Mitosis Mad2 growth APC-P unaligned chromosomes Mcm1 Cdc20 Cdh1 Clb2 APC Inactive trimer Cdc14 and Cln3 Swi5 CDKs SCF P Cdc14 Bck2 Inactive trimer ? MBF Clb5 DNA synthesis Clb2 SBF Cln2 Budding

  22. Pds1 Esp1 Cdc14 RENT Sic1 Sic1 P Esp1 Sister chromatid separation unaligned chromosomes SBF Cdh1 Pds1 Mcm1 Cdc20 PPX Net1P Mutants Tem1-GDP Cdc15/MEN Lte1 Bub2 Tem1-GTP Net1 Mcm1 Cdh1 Cdc20 Cln2 Clb2 Clb5 Mitosis Mad2 growth APC-P unaligned chromosomes Mcm1 Cdc20 Cdh1 Clb2 APC Inactive trimer Cdc14 and Cln3 Swi5 CDKs SCF P Cdc14 Bck2 Inactive trimer ? MBF Clb5 DNA synthesis Clb2 SBF Cln2 Budding

  23. Pds1 Esp1 Cdc14 RENT Sic1 Sic1 P Esp1 Sister chromatid separation unaligned chromosomes SBF Cdh1 Pds1 Mcm1 Cdc20 PPX Net1P Mutants Tem1-GDP Cdc15/MEN Lte1 Bub2 Tem1-GTP Net1 Mcm1 Cdh1 Cdc20 Cln2 Clb2 Clb5 Mitosis Mad2 growth APC-P unaligned chromosomes Mcm1 Cdc20 Cdh1 Clb2 APC Inactive trimer Cdc14 and Cln3 Swi5 CDKs SCF P Cdc14 Bck2 Inactive trimer ? MBF Clb5 DNA synthesis Clb2 SBF Cln2 Budding

  24. Pds1 Esp1 Cdc14 RENT Sic1 Sic1 P Esp1 Sister chromatid separation unaligned chromosomes SBF Cdh1 Pds1 Mcm1 Cdc20 PPX Net1P Mutants Tem1-GDP Cdc15/MEN Lte1 Bub2 Tem1-GTP Net1 Mcm1 Cdh1 Cdc20 Cln2 Clb2 Clb5 Mitosis Mad2 growth APC-P unaligned chromosomes Mcm1 Cdc20 Cdh1 Clb2 APC Inactive trimer Cdc14 and Cln3 Swi5 CDKs SCF P Cdc14 Bck2 Inactive trimer ? MBF Clb5 DNA synthesis Clb2 SBF Cln2 Budding

  25. Accurate account of the properties of >100 mutant cells; correctly predicts properties of new mutant combinations

  26. Designer Drugs Taxol Cancer Information Processing System What use is the new systems biology? Hanahan & Weinberg (2000)

  27. The impact of the new systems biology on biomedicine, pharmaceuticals and homeland security may, some day, be as great as the impact of modern weather prediction on transportation, military preparedness and civil defense.

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