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11/13 - Seminar (physical): Norbert Scherer, University of Chicago

Norbert Scherer - Scherer Group website
Department of Chemistry
University of Chicago
Host: Haw Yang

Statistical mechanical insights into the bacterial cell cycle: fluctuations and scaling

The genomics revolution has greatly empower the determination of molecularly detailed biochemical reaction networks for many organisms and functions. This information allows defining a "structural topology" of the network (with implicit assumptions). A long standing complementary approach in the physical sciences involves reverse engineering electrical or molecular "black boxes" by signal analysis: i.e. determining the response of an unknown system to various inputs (e.g. pulses, sinusoidal). The latter can also be thought of as information processing by a network and can yield a "functional topology". We have developed a "chemical perturbation spectroscopy" that allows elucidating the response function of the cell cycle (network) Caulobacter crecentus from single cell measurements in a microfluidic flow environment. The results allow the development of a minimalist functional topology. Surprisingly, the existent molecular detailed network models fail to capture our measured response functions. We have also performed nutrient pulsing and temperature dependent measurements on the same system to begin to address fundamental questions concerning irreversibility and noise and energy utilization in this nonequilibrium steady-state process. We find surprising scaling relationships yet Arrhenius behavior, and a strong ratio sensing as opposed to fixed cell size mechanism for cell growth. We also establish cell immortality (for ~100 generations) yet senescence under controlled stress conditions. A surprisingly simple Langevin-like model is developed that relates the thermal results to a fluctuation perspective of the cell growth process. Fluctuation-dissipation experiments for chemical and nutrient perturbations will be discussed if time permits.