Leveraging and coping with uncertainty in the response of individual cells to therapy

Non-genetic heterogeneity fluctuates over diverse timescales, ranging from hours to months. In specific cases, such variability can profoundly impact the response of cell populations to therapy, in both antibiotic treatments in bacteria and chemotherapy in cancer. It is thus critical to understand the way phenotypes fluctuate in cell populations and the molecular sources of phenotypic diversity. Technical and analytical breakthroughs in the study of single cells have leveraged cellular heterogeneity to gain phenomenological and mechanistic insights of the phenotypic transitions that occur within isogenic cell populations over time. Such an understanding moves forward our ability to design therapeutic strategies with the explicit goal of preventing and controlling the selective expansion and stabilization of drug-tolerant phenotypic states.