title: Revisiting bistability in the lysis/lysogeny circuit of bacteriophage lambda.
abstract: The lysis/lysogeny switch of bacteriophage lambda serves as a paradigm for binary cell fate decision, long-term maintenance of cellular state and stimulus-triggered switching between states. In the literature, the system is often referred to as "bistable." However, it remains unclear whether this term provides an accurate description or is instead a misnomer. Here we address this question directly. We first quantify transcriptional regulation governing lysogenic maintenance using a single-cell fluorescence reporter. We then use the single-cell data to derive a stochastic theoretical model for the underlying regulatory network. We use the model to predict the steady states of the system and then validate these predictions experimentally. Specifically, a regime of bistability, and the resulting hysteretic behavior, are observed. Beyond the steady states, the theoretical model successfully predicts the kinetics of switching from lysogeny to lysis. Our results show how the physics-inspired concept of bistability can be reliably used to describe cellular phenotype, and how an experimentally-calibrated theoretical model can have accurate predictive power for cell-state switching.
authors: Department of Physics, University of Illinois, Urbana, Illinois, United States of America.
authors: Michael
authors: M
authors: Bednarz
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Jennifer A
authors: JA
authors: Halliday
authors: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Christophe
authors: C
authors: Herman
authors: Department of Physics, University of Illinois, Urbana, Illinois, United States of America; Center for the Physics of Living Cells, University of Illinois, Urbana, Illinois, United States of America; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Ido
authors: I
authors: Golding
mesh_terms: D001433:Bacteriolysis / Q000235:genetics*; D010582:Bacteriophage lambda / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D005809:Genes, Regulator; D005812:Genes, Switch; D007700:Kinetics; D008242:Lysogeny / Q000235:genetics*; D008962:Models, Theoretical; D014775:Virus Activation