Theoretical and experimental analysis of the phage lambda genetic switch implies missing levels of co-operativity

The behavior of the cro-repressor switch in phage lambda, a temperate phage of Escherichia coli, is described at the organismal level within a dynamical system framework. The molecular biology of the switch has been well characterized up to the level of the regulation of transcription initiation. In this paper we construct a description of a lysogen whose prophage is mutated in certain genes, so that the switch is functionally isolated from the rest of the phage genome. Such a lysogen has two stable epigenetic states, and comparison of the theory with measurements of intracellular cro concentration corresponding to one of these states suggest that additional levels of regulation, not included in the current description of the switch, should exist for this system. In addition, we suggest a new method for the measurement of intracellular concentrations.