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