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9/20 - Seminar (physical): Norbert Scherer, University of Chicago

Norbert Scherer - speaker's website
Department of Chemistry
University of Chicago
Host: Haw Yang

Elucidating Quantitative Rules of a Bug’s Life by Chemical Perturbation Spectroscopy

Understanding the functional aspects of cells as autonomous nonequilibrium systems requires knowing more than just the molecular players and their partner interactions. Rather, new insights emerge from a "modular cell biology" perspective as proposed by Hopfield et al. (Nature, 402, 1999). In this talk I will illustrate how rules of organization of oscillators in regulatory biochemical networks emerge from measurements at the organismal level; that is, viewing the "forest rather than the trees." Furthermore, we have developed a large data set microscopy and image analysis capability for measurement of large numbers of single cells of the organism Caulobacter crecentus. With this we are now able to elucidate fundamental insights about cell growth with high statistical precision. The inherent nonequilibriumness of the single cell growth, the metabolic drive, is captured by a proposed biochemical mechanism. Our statistical mechanical description of an autocatalytic cycle, based on the deterministic form published by Hinshelwood, yields nontrivial predictions of temperature-dependence of the growth and division time distributions, a scaling relation of the distributions and a measure of the nonequilibriumness of cell growth. Finally, I will illustrate ongoing work on developing the chemical perturbation approach used in the studies above into a nonlinear spectroscopy; i.e., showing correlation on the timescale of several cell cycles, that the response (response functions) obeys a Fluctuation-Dissipation theorem relation and that the chemical pulsing approach can lead to transient responses of biochemical networks (particularly metabolic ones) that do not have an analog in more typical steady-state measurements.