THEORETICAL ANALYSIS OF FUNCTIONAL MODULES

Harvard University, Cambridge MA

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Abstract

This proposal will establish a productive dialogue between experiment and theory, create models that predict the behavior of biological systems, and develop tools that explain how such models work. The studied modules are of three classes: those that perform Boolean functions, those that quantitatively measure parameters in the internal or external environment, and those that give analog control of biological processes. Modeling these different sorts of module permits comparisons of the principles that lie behind their function. Those that are shared will be candidates for general, explanatory principles that the group is especially interested in finding. In all cases, studies will use both numerical and analytic methods with iterative cycles between the two approaches leading to progressively broader understanding of the principles that the different modules embody. 1) Boolean modules: The subject modules control Drosophila development (segmentation and dorso-ventral patterning) or are synthetic modules that will be studied in Project 5. In all cases, the goal is to find and then generalize analytical tools that can predict whether a particular set of variables will allow the module to perform its normal function, fail, or perform a novel, and perhaps evolutionarily useful, function. 2) Measurement modules: The subject modules detect concentrations gradients in bacteria and yeast (Project 3). They monitor temporal and spatial changes, respectively, have evolved independently of each other, and are understood to very different extents. Studying both will compare the role of theory at early and late stages of understanding, and search for common principles that must reflect the operation of evolutionary constraints. 3) Analog modules: The subject module is responsible for assembling a mitotic spindle of a predetermined length. Theory and experiment will combine to discriminate between qualitatively different models and then refine the correct one.