Nonlinear dynamics and stochastic fluctuations in gene regulatory networks
Alexander Karlshofer, Jan Ribbe
Individual cells within an isogenic cell population can launch different genetic programs that determine cell fate. Phenotypic bistability in genetically identical populations controls development of eukaryotic cells, virus latency, and bacterial sporulation and competence for DNA transformation. We are studying the development of competence for DNA transformation in Bacillus subtilis.
When cell density is high a well-defined fraction of cells expresses proteins that are required to assemble the DNA import machine; this competent fraction of the bacterial cell population expresses the master regulator for DNA uptake proteins, ComK, at high level. A genetic switch is implemented by nonlinear amplification of the master regulator ComK: in the B-state low expression of ComK is low and in the K-state expression of ComK is high. Using a fluorescent reporter for the master regulator we have shown that expression in the B-state is noisy and that that basal expression sets a switching window. We are currently combining quantitative microscopy with nonlinear dynamics simulations to investigate how perturbations of the regulatory network and external conditions influence stability and switching kinetics.
Techniques
- Quantitative image analysis
Collaborations
Publications
Maier, B. Competence and transformation. in Bacillus: Cellular and Molecular Biology, ed. Peter Graumann, Caister University Press (2011)
Maier, B. Stochastische Differenzierung als bakterielle Überlebensstrategie. Biospektrum 2/2010
Leisner, M., Kuhr, J.-T., Radler, J.O., Frey, E., Maier, B. Kinetics of genetic switching into the state of bacterial competence. Biophys. J. 96(3), 1178-1188 (2009)
Leisner, M., Stingl, K., Frey, E., Maier, B. Stochastic switching to competence. Curr. Opin. Microbiol. 11(6), 553-559 (2008)
Leisner, M., Stingl, K., Rädler, J.O. and Maier, B. Basal expression rate of comK sets a ‘switching-window’ into the K-state of Bacillus subtilis. Mol. Microbiol. 63(6), 1806-1816 (2007)