Probing the Cell-Fate Decision During Infection of E. coli by the Virus Lambda

Lambda is a virus which infects E. coli bacteria, and its infection serves as a paradigm for cell-fate decisions, processes where cells select and transition to stable states. Infected cells can proceed along one of two developmental pathways: lysis, characterized by rampant viral replication and eventual cell death, or lysogeny, characterized by viral dormancy. Despite the decades of research done on this system, fundamental questions remain about what factors drive the decision and the mechanisms by which they act. We are developing models which, calibrated by single-cell resolution experimental data, will be able to shed light on how currently known factors (such as gene copy number, both as an initial condition and as a function of time due to replication, as well as cell volume) influence the decision process, and predict additional factors. We are also investigating explanations for a surprising observation in lambda – the scaling of the probability of a lysogenic outcome with viral concentration exhibits a complicated structure, which can be understood by positing that viruses independently decide their fates. We are developing simple models to test this hypothesis and propose a possible physical mechanism for this intracellular individuality.