"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 Predictions Dynamics of Cellular Structures and Molecules Simulation Hypothesis (Model) 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 cytoskeletal mechanics regulated? Experiment Trends in Cell Biology 13: (2003)

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’

“Cell and tissue, shell and bone, leaf and flower, are so many portions of matter, and it is in obedience to the laws of physics that their particles have been moved, moulded and conformed. They are no exceptions to the rule that God always geometrizes. Their problems of form are in the first instance mathematical problems, their problems of growth are essentially physical problems, and the morphologist is, ipso facto, a student of physical science. “ -- D’Arcy Wentworth Thompson, On Growth and Form, 1917

"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