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

• 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

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

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)

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

Methodology

• Splitting up the work• Other thoughts??

Pathways we won’t present

T-Cell Receptors

Alon, An Introduction to Systems Biology.

Kinetic Proofreading in T-Cell Receptors

Alon, An Introduction to Systems Biology.

FceRI

HMGB1