Modelling the genetic switch of bacteriophage TP901-1 – Niels Bohr Institute - University of Copenhagen

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Modelling the genetic switch of bacteriophage TP901-1

TP901-1 is a temperate bacteriophage infecting bacteria of Lactococcus lactis subsp. cremoris. As other temperate phages TP901-1 enters one of two pathways upon infection of a sensible host. The phage can kill the infected cell as the phage reproduces, or it may persist in the host like a prophage. The initial choise between the two pathways is centered at the genetic switch of the phage consisting of two divergently oriented promoters, PR and PL, the phage repressor CI and a protein termed MOR. Phage TP901-1 has been explored for more than two decades, but the underlying mechanisms of the genetic switch is not yet fully understood.

In the thesis the bistable genetic switch of L. lactis phage  TP901-1 was explored with the combined tools of biochemistry and biophysics. Experiments on the effect of different CI levels on PR and PL promoter activities revealed unexpectedly, that the presence of MOR prevents the repression of PR and PL, for CI concentration beyond the CI level of PR repression in the absence of MOR. Through statistical mechanical modelling three hypotheses on the underlying mechanisms of the genetic switch were examined. The models suggest a sofar unappreciated importance of the distant operator site, OD, in keeping the PR promoter open at low concentrations of CI, and exclude cooperative binding of CI and MOR at the putative OM site, as the only action of MOR in preventing the repression of the promoters. A final model, based on the compeeting formation of a CI-MOR heterodimer, is presented as a possible description of the underlying mechanisms of the experimental data.¨


Supervisors: Kim Sneppen (NBI) and Karin Hammer (DTU)