Transcriptional bursting and bacterial adaptation
Last modified: 2014-06-09
Abstract
One of the most puzzling stories of molecular biology relates to the variability of gene expression in populations of clone cells.
As discussed by Max Delbrück, this non genetic variability has a physical origin and demonstrates the discontinuous functioning of biosynthetic mechanisms.
With the advent of modern fluorescence microscopy technology, this “expression noise” can be quantified with unprecedented precision.
We use 2psN&B fluctuation microscopy methods for measuring cell-to-cell phenotypic variations in gene expression, even for very weakly transcribed genes under strong repression. We particularly focus on regulators of the central carbon metabolism in Bacillus subtilis. Bacterial response to changes of the carbon source is a switch between different metabolic pathways. For two promoters representing the main control points of this metabolic switch, the observed distributions of gene expression are strongly skewed, suggesting transcriptional bursting in both permissive and repressive conditions. The dynamical changes of bacterial populations under such switches have to be considered at collective and multiscale levels, that is quite a challenge for mathematical and physical modeling. We will discuss models and general rules that on one hand relate gene expression noise patterns and transcriptional regulation mechanisms and on the other hand elucidate how expression variability
is exploited in bacterial adaptation strategies.
References
1) M.L. Ferguson, D. Le Coq, M. Jules, S. Aymerich, O.Radulescu, N. Declerck, C.A. Royer. Reconciling molecular regulatory mechanisms with noise
patterns of bacterial metabolic promoters in induced and repressed states, Proceedings of the National Academy of Sciences USA (2012) 109: 155.
2) O.Radulescu, GCP Innocentini, JEM Hornos. Relating network rigidity, time scale hierarchies, and expression noise in gene networks,
Physical Reviews E 85 (2012) 041919.
3) A.Crudu, A.Debussche, O.Radulescu, Hybrid stochastic simplifications for multiscale gene networks, BMC Systems Biology (2009) 3:89.
As discussed by Max Delbrück, this non genetic variability has a physical origin and demonstrates the discontinuous functioning of biosynthetic mechanisms.
With the advent of modern fluorescence microscopy technology, this “expression noise” can be quantified with unprecedented precision.
We use 2psN&B fluctuation microscopy methods for measuring cell-to-cell phenotypic variations in gene expression, even for very weakly transcribed genes under strong repression. We particularly focus on regulators of the central carbon metabolism in Bacillus subtilis. Bacterial response to changes of the carbon source is a switch between different metabolic pathways. For two promoters representing the main control points of this metabolic switch, the observed distributions of gene expression are strongly skewed, suggesting transcriptional bursting in both permissive and repressive conditions. The dynamical changes of bacterial populations under such switches have to be considered at collective and multiscale levels, that is quite a challenge for mathematical and physical modeling. We will discuss models and general rules that on one hand relate gene expression noise patterns and transcriptional regulation mechanisms and on the other hand elucidate how expression variability
is exploited in bacterial adaptation strategies.
References
1) M.L. Ferguson, D. Le Coq, M. Jules, S. Aymerich, O.Radulescu, N. Declerck, C.A. Royer. Reconciling molecular regulatory mechanisms with noise
patterns of bacterial metabolic promoters in induced and repressed states, Proceedings of the National Academy of Sciences USA (2012) 109: 155.
2) O.Radulescu, GCP Innocentini, JEM Hornos. Relating network rigidity, time scale hierarchies, and expression noise in gene networks,
Physical Reviews E 85 (2012) 041919.
3) A.Crudu, A.Debussche, O.Radulescu, Hybrid stochastic simplifications for multiscale gene networks, BMC Systems Biology (2009) 3:89.