The production of proteins in bacteria is largely controlled by the regulation of gene transcription, via the binding of protein "transcription factors" to the DNA. This network of regulatory interactions allows the bacterium to control its internal processes and interact with the environment in a sophisticated way. The production and degradation of transcription factors is, however, strongly affected by the cell cycle. During the cell cycle, the DNA in the cell is copied and the cell volume doubles, before the cell divides in two. Although these events must have important and striking consequences for the performance of bacterial gene networks, these effects have hardly been addressed either theoretically or experimentally.
In this project, a combined simulation and experimental approach is proposed, to investigate the effect of the cell cycle on gene networks in the bacterium Escherichia coli. We will use advanced simulation techniques, including a method developed by me during my Marie Curie Fellowship, to predict the growth-rate dependence of the performance of two simple, representative gene circuits: an auto-repressor loop and a bistable switch. In parallel, experiments will be carried out to incorporate already existing gene circuits onto the chromosome of E. coli, in order to measure their behaviour for different bacterial growth rates. For the auto-repressor, the output will be the average repressor concentration and the variation among cells in a genetically identical population; for the switch, it will be the spontaneous flipping rate. The results will be compared directly to simulation predictions.
The project aims at a quantitative understanding of the performance of gene networks, for cells in "real-life" situations of growth and division. We seek to bridge the gap between the current simple models and naturally occurring gene networks. Integration of high-level theoretical work with experiments makes this a very exciting proposal.
Field of science
- /natural sciences/biological sciences/genetics and heredity/dna
- /natural sciences/biological sciences/microbiology/bacteriology
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
- /natural sciences/biological sciences/genetics and heredity/chromosome
- /natural sciences/mathematics/applied mathematics/mathematical model
Call for proposal
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