LIBST Seminar

Frank DELVIGNE (ULiège, Gembloux Agro-BIO TECH): Directing microbial cell decision-making process at a single cell resolution under nutrient limiting conditions.

Terra research and teaching centre, Microbial Processes and Interactions (MiPI), Gembloux Agro‑Bio Tech, University of Liège, Gembloux, Belgium.

With the advent of systems and synthetic biology, gene circuits exhibiting complex behavior circuitry have been designed and artificial parts have been developed for controlling the activity of individual cells. However, the functions associated with these gene circuits are typically loss on the long run due to phenotypic diversification and/or evolutionary pressure. As a first case study, the gene circuit responsible for the switch from glucose to arabinose in E. coli will be investigated. When cultivated in chemostat on a mixture of two carbon sources, cells tend to adapt to the most efficient one, i.e. glucose. As a result, the proteins associated with the arabinose operon are progressively lost. However, when using glucose/arabinose pulsing driven by automated single cell analyses, it is possible to maintain 100% of the population in the activated state over more than 60 generations in continuous cultivation. These data show that effective cell-machine interface can be used for influencing cell decision-making processes in dynamic conditions. In a second time, this concept will be extended to other phenotypic features (i.e., outer membrane permeabilization upon nutrient limitation) and to other organisms (i.e., response of yeast population to nutrient stress) in order to demonstrate the broad applicability of the interface.

Beside its potential usefulness for controlling microbial population for biomanufacturing, the data gathered by the cell-machine interface can be used for a better characterization of the dynamic behavior of gene circuits and the design of more efficient, synthetic, ones.