Section: Research Program

Natural and engineered control of regulatory networks

Participants : Cindy Gomez Balderas-Barillot, Eugenio Cinquemani, Johannes Geiselmann [Correspondent] , Edith Grac, Nils Giordano, Hidde de Jong, Stéphan Lacour, Delphine Ropers, Alberto Soria-Lopéz.

In the previously-described objectives, we have focused on identifying complex regulatory networks and gaining a better understanding of how the network dynamics underlies the observable behavior of the cell. Based on the insights thus obtained, a complementary perspective consists in changing the functioning of a bacterial cell towards a user-defined objective, by rewiring and selectively perturbing its regulatory networks. The question how regulatory networks in microorganisms can be externally controlled using engineering approaches has a long history in biotechnology and is receiving much attention in the emerging field of synthetic biology.

Within a number of on-going projects, IBIS is focusing on two different questions. The first concerns the development of growth-rate controllers of bacterial cells. Since the growth rate is the most important physiological parameter in microorganisms, a better understanding of the molecular basis of growth-rate control and the engineering of open-loop and closed-loop growth-rate controllers is of major interest for both fundamental research and biotechnological applications. Second, we are working on the development of methods with a solid foundation in control theory for the real-time control of gene expression. These methods are obviously capital for the above-mentioned design of growth-rate controllers, but they have also been applied in the context of a platform for real-time control of gene expression in cell population and single cells, developed by the Inria project-team CONTRAINTES, in collaboration with a biophysics group at Université Paris Descartes.