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Acquired Capabilities

Acquired Capabilities. Hanrahan and Weinberg, “Hallmarks of Cancer,” Cell, 2000. Pathways. Hanrahan and Weinberg, “Hallmarks of Cancer,” Cell, 2000. Pathways. EGFR : DNA synthesis and cell proliferation look for activation of Sos or Ras Spratt, Balmick , Ratsimihah

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Acquired Capabilities

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  1. Acquired Capabilities Hanrahan and Weinberg, “Hallmarks of Cancer,” Cell, 2000.

  2. Pathways Hanrahan and Weinberg, “Hallmarks of Cancer,” Cell, 2000.

  3. Pathways • EGFR: DNA synthesis and cell proliferation • look for activation of Sos or Ras • Spratt, Balmick, Ratsimihah • TCR: antigen recognition • Look for activation of Erk • Packer, Rodriguez, Yalkabov • FcεRI: immune response • Look for activation of Syk • Feitzinger, Abbasi, Nunez • Apoptosis: cell death • Look for activation of • Miranda, Garib, Green • HMGB1: inflammation • Look for activation of ? • Weinberg, Zegel, Lagrange

  4. Project Goal • Develop a probability distribution for “first passage times” by running many simulations • First passage time is the time the target protein reaches a given level of activation • Variations: • Vary ligand dose • Vary level of activation • Eliminate backward reactions • Put some molecules in an “always-on” or “always-off” state • An experiment will consist of varying one thing and developing the probability distribution for each value

  5. Methodology • SSA simulations of assigned pathway using BioNetGen • Scripts developed for multiple runs and collecting data • Creates a directory for each run • Data collection program creates file for histogram • Use RuleBender for initial explorations • Find equilibrium values for inactive state with ODE • Find appropriate time interval (balance time to run with getting enough data)

  6. Methodology • Saving data • One directory for each experiment • One subdirectory for each value of variable • README in toplevel directory explaining what the variable and the values are plus any problems that arose • Histogram in top-level directory • In parallel: read about pathway • Wikipedia • Books • Papers

  7. Methodology • Splitting up the work • Other thoughts??

  8. Pathways we won’t present

  9. T-Cell Receptors Alon, An Introduction to Systems Biology.

  10. Kinetic Proofreading in T-Cell Receptors Alon, An Introduction to Systems Biology.

  11. FceRI

  12. HMGB1

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