Monday, October 21, 2013
Quantitative predictive understanding of bacterial growth physiology
Terence Hwa, Professor, Department of Physics and Molecular Biology, University of California, San Diego
The ultimate goal of systems biology is to attain a quantitative, predictive understanding of the behavior of a living system as a whole (i.e., physiology) from its molecular parts. A major obstacle to this endeavor is the enormous number of (mostly inaccessible) parameters underlying complex biological systems. My lab has tried to tackle this problem using a top-down approach starting from cellular physiology. In this talk, I will show how a simple phenomenological approach in the spirit of thermodynamics can provide quantitative, predictive understanding of the physiological behaviors of bacteria cells. I will present a number of linear relations describing the allocation of cellular resources for exponentially growing E. coli cells. With a few phenomenological parameters, these "growth laws" can be used to accurately predict the physiological responses to various perturbations, including the fitness effect of protein over-expression, and the abrupt cellular response to the application of antibiotics. Applying the top-down approach to the endogenous response of E. coli to different modes of nutrient limitation, we reveal key molecular interactions enabling seamless coordination between different branches of metabolism -- interactions which Monod pursued until the end of his life but remained elusive despite decades of extensive molecular studies.