MSSセミナー@京都 #06


  • 2008年05月 30日(金)14:30〜16:00


講師: Dr. Rosalind Allen (The University of Edinburgh)


Simulating the flipping of the bacteriophage lambda genetic switch


Bacteriophage lambda is a virus that infects the bacterium Escherichia coli.It is a paradigm for developmental biology because it has two alternativemodes of living - the lysogenic state, in which it integrates its DNA intothe E. coli chromosome and lives stably, and the lytic state, where itreplicates and kills the E. coli cell. We have constructed a stochasticsimulation model for the genetic regulatory network that controls thetransition from lysogeny to lysis. This network is bistable and subject torandom fluctuations, but it has been found experimentally to be extremelystable, flipping spontaneously less than once in 10^9 bacterial generations!We have used the Forward Flux Sampling rare event simulation method tocalculate the spontaneous flipping rate. Our results highlight the need toconsider nonspecific DNA binding, DNA looping and macromolecular crowding inorder to get the "right" answer, leading to some general conclusions aboutstochastic modelling of gene regulatory networks.