Ribosomes---the primary macromolecular machines responsible for translating the genetic code into proteins---are complexes of precisely folded RNA and proteins.  The ways in which their production and assembly are managed by the living cell is of deep biological importance.  Here we extend our recent spatially resolved whole-cell model of ribosome biogenesis  to include the effects of growth, DNA replication, and cell division in slow growing E. coli.  . In order to determine the replication parameters, we construct and analyze a series of bacterial strains with fluorescently labeled genes distributed evenly throughout their chromosomes.  By measuring these cells' lengths and number of gene copies at the single-cell level, we could fit a statistical model of the initiation and duration of chromosome replication.  We found that for our slow-growing bacteria with 120 minute doubling time, replication was initiated 42 minutes into the cell cycle and completed after an additional 42 minutes.  All biological processes are described in terms of reaction-diffusion master equations and solved stochastically using the Lattice Microbes simulation software which allows us to capture the dynamics of the cellular states at various stages of the cell cycle.

Ribosome biogenesis in replicating cells: Integration of experiment and theory

253rd National Meeting (2017)

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