Bulletin of the American Physical Society
2009 APS March Meeting
Volume 54, Number 1
Monday–Friday, March 16–20, 2009; Pittsburgh, Pennsylvania
Session B7: Bacterial Growth Laws and Systems Biology |
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Sponsoring Units: DBP Chair: Terence Hwa, University of California, San Diego Room: 407 |
Monday, March 16, 2009 11:15AM - 11:51AM |
B7.00001: to be determined by you Invited Speaker: |
Monday, March 16, 2009 11:51AM - 12:27PM |
B7.00002: Growth laws and mechanisms of global control in bacteria Invited Speaker: The growth laws of Schaechter, Maal{\o}e and Kjeldgaard are among the most striking discoveries in bacterial growth physiology: cell composition (mass/cell, RNA/cell, etc.) is a simple function of growth rate alone -- irrespective of how that growth rate is established. I will review the growth laws, and discuss recent experiments that have uncovered new laws. A systems-level mathematical model is developed that suggests the growth laws arise from the partitioning of the protein synthesizing machinery of the cell (the ribosomes), and furthermore indicates a deep connection between growth rate control and central metabolism. [Preview Abstract] |
Monday, March 16, 2009 12:27PM - 1:03PM |
B7.00003: Growth-rate dependent effects on bacterial gene expression Invited Speaker: For fast growing bacteria, which can adapt to wildly different growth conditions, changes in gene expression are often accompanied by changes in growth rates. Because the macroscopic composition of bacteria (e.g., cell size, ribosome concentration, gene copy number) is known to vary greatly for bacteria grown at different rates, significant changes in gene expression may arise 'passively' just due to the growth rate change alone. Towards a quantitative understanding of these passive effects, we analyzed quantitatively available data for the growth rate dependence of various macroscopic parameters affecting gene expression in E. coli, and predicted the growth-rate dependence of gene expression for various simple genetic circuits. For a constitutively expressed gene, the expressed protein concentration is decreased at faster growth, while weak growth-rate dependence is obtained for autorepressing genes and genes under negative control by an autorepressor. We also studied the growth-rate dependence of bistable genetic circuits and determined conditions such that bistability is found over a wide range of growth rates. Our results demonstrate that growth-rate dependent effects play an important role and must be taken into account when analyzing gene expression data under different condition. Buffering against these growth rate dependent effects may be an important requirement underlying the robust operation of endogenous genetic circuits in these bacteria, and should be a prime factor to consider in the design of robust, synthetic circuits. [Preview Abstract] |
Monday, March 16, 2009 1:03PM - 1:39PM |
B7.00004: A Coarse-Grained Biophysical Model of \textit{E. coli} and Its Application to Perturbation of the rRNA Operon Copy Number Invited Speaker: In this work a biophysical model of \textit{Escherichia coli} is presented that predicts growth rate and an effective cellular composition from an effective, coarse-grained representation of its genome. We assume that \textit{E. coli} is in a state of balanced exponential steady-state growth, growing in a temporally and spatially constant environment, rich in resources. We apply this model to a series of past measurements, where the growth rate and rRNA-to-protein ratio have been measured for seven \textit{E. coli} strains with an rRNA operon copy number ranging from one to seven (the wild-type copy number). These experiments show that growth rate markedly decreases for strains with fewer than six copies. Using the model, we were able to reproduce these measurements. We show that the model that best fits these data suggests that the volume fraction of macromolecules inside \textit{E. coli} is not fixed when the rRNA operon copy number is varied. Moreover, the model predicts that increasing the copy number beyond seven results in a cytoplasm densely packed with ribosomes and proteins. Assuming that under such overcrowded conditions prolonged diffusion times tend to weaken binding affinities, the model predicts that growth rate will not increase substantially beyond the wild-type growth rate, as indicated by other experiments. Our model therefore suggests that changing the rRNA operon copy number of wild-type \textit{E. coli} cells growing in a constant rich environment does not substantially increase their growth rate. Other observations regarding strains with an altered rRNA operon copy number, such as nucleoid compaction and the rRNA operon feedback response, appear to be qualitatively consistent with this model. In addition, we discuss possible design principles suggested by the model and propose further experiments to test its validity. [Preview Abstract] |
Monday, March 16, 2009 1:39PM - 2:15PM |
B7.00005: Dynamics of bacterial gene regulation Invited Speaker: The phenomenon of diauxic growth is a classical problem of bacterial gene regulation. The most well studied example of this phenomenon is the glucose-lactose diauxie, which occurs because the expression of the lac operon is strongly repressed in the presence of glucose. This repression is often explained by appealing to molecular mechanisms such as cAMP activation and inducer exclusion. I will begin by analyzing data showing that these molecular mechanisms cannot explain the strong lac repression because they exert a relatively weak effect. I will then present a minimal model accounting only for enzyme induction and dilution, which yields strong repression despite the absence of catabolite repression and inducer exclusion. The model also explains the growth patterns observed in batch and continuous cultures of various bacterial strains and substrate mixtures. The talk will conclude with a discussion of the experimental evidence regarding positive feedback, the key component of the minimal model. [Preview Abstract] |
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