Acquired Capabilities

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 species 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 • Histogram in top-level directory

7. Methodology • Other thoughts??

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

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

10. FceRI

11. HMGB1