Section: New Results

Control of regulatory networks in bacteria

A bacterial cell adapts its growth rate to the environment, notably to the availability of nutrients providing the molecular building blocks and the energy required for growth. Upon a change in the environment, the global physiology of the cell is adjusted in parallel with the adaptation of the growth rate. In the context of the PhD thesis of former IBIS member Jérôme Izard, we have studied the relation between the gene expression machinery, the global physiology of the cell, and the growth rate from a different perspective. Our aim was to change the mechanisms regulating the activity of the gene expression machinery in such a way so as to be able to externally control the growth rate of the cell.

More precisely, we have engineered an E. coli strain in which the transcription of an essential component of the global gene expression machinery, RNA polymerase, is under the tight control of an inducible promoter. By adjusting the inducer concentration in the medium we can adjust the RNA polymerase concentration and thereby reversibly tune the growth rate of the bacterium between zero and the maximal growth rate. The growth arrest is completely reversed when RNA polymerase is provided again. The analysis of the transcriptome at growth rates restricted by the concentration of RNA polymerase confirms that the concentration of RNA polymerase is the major determinant of changes in gene expression patterns. Our modified E. coli strain provides a novel way of setting growth rate in a tunable, reversible, modular, and medium-independent way. The strain, described in a paper submitted for publication, opens new perspectives for studying the mechanisms of growth control as well as for developing biotechnological applications, the subject of the post-doctoral fellowship of Cindy Gomez Balderas-Barillot. We have submitted a patent proposing such applications, which underlies the technology transfer activities undertaken in the recently-started Reset project (Section  8.2 ).