Download Intro: Signal Fusion within the Cell

"Every attempt to employ mathematical
methods in the study of biological
questions must be considered profoundly
irrational and contrary to the spirit of
biology.
“If mathematical analysis should ever hold
a prominent place in biology - an
aberration which is happily almost
impossible - it would occasion a rapid and
widespread degeneration of that science"
-- Auguste Comte, Pilosophie Positive, 1830
The Problem
Quantitative Cell Biology
Hypothesis (Model)
Experiment
Predictions
Dynamics of Cellular
Structures and Molecules
Simulation
• What are the initial concentrations,
diffusion coefficients and locations of
all the implicated molecules?
• What are the rate laws and rate
constants for all the biochemical
transformations?
• How are the forces controlling
Trends in Cell Biology 13:570-576 (2003) cytoskeletal mechanics regulated?
How Can Computation Help Cell Biologists?
• Formulate a quantitative hypothesis (i.e. a
model), make quantitative predictions
(simulations), test them experimentally.
• Analyze quantitative microscopy experiments
– FRAP, uncaging, probe translocation
• Visualize species that can’t be probed
experimentally
– Spatiotemporal patterns of post-translational
modifications
• Probe complex pathways and networks
– Identify global or emergent network properties
– Virtual knockouts; evaluate drug targets in silico
• Facilitate the sharing of models and the
collaborative construction of ‘supermodels’
"I only claim that in any
particular discipline you can
meet only as much science as
there is mathematics."
Immanuel Kant
"What are we to do with the enormous
cornucopia of genes and molecules we
have found in living cells? How can we
see the wood for the trees and
understand complex cellular processes?
.... Although we poor mortals have
difficulty manipulating seven things in
our head at the same time, our silicon
protégés do not suffer this limitation.
...The data are accumulating and the
computers are humming. What we lack
are the words, the grammar and the
syntax of the new language."
-- Dennis Bray, 1997