Transcription factors (TFs) are proteins that regulate the expression of genes by binding sequence-specific sites on the chromosome. It has been proposed that to find these sites fast and accurately, TFs combine one-dimensional (1D) sliding on DNA with 3D diffusion in the cytoplasm. This facilitated diffusion mechanism has been demonstrated in vitro, but it… (More)
We have developed a method combining microfluidics, time-lapsed single-molecule microscopy and automated image analysis allowing for the observation of an excess of 3000 complete cell cycles of exponentially growing Escherichia coli cells per experiment. The method makes it possible to analyse the rate of gene expression at the level of single proteins over… (More)
SUMMARY MesoRD is a tool for simulating stochastic reaction-diffusion systems as modeled by the reaction diffusion master equation. The simulated systems are defined in the Systems Biology Markup Language with additions to define compartment geometries. MesoRD 1.0 supports scale-dependent reaction rate constants and reactions between reactants in… (More)
Physical modeling is increasingly important for generating insights into intracellular processes. We describe situations in which combined spatial and stochastic aspects of chemical reactions are needed to capture the relevant dynamics of biochemical systems.
We have investigated which aspects of transcription factor DNA interactions are most important to account for the recent in vivo search time measurements for the dimeric lac repressor. We find the best agreement for a sliding model where non-specific binding to DNA is improbable at first contact and the sliding LacI protein binds at high probability when… (More)