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