page 497) discovered a new type of oscillatory process that can control gene expression. In addition to creating a computational model that should help to direct future studies of cell stress, the authors identified a sort of biological Heisenberg effect, in which the process of observing certain cells under the microscope could significantly influence their physiology.
In the yeast Saccharomyces cerevisiae, two related transactivators, Msn2 and Msn4, translocate from the cytoplasm to the nucleus in response to a wide variety of stresses. Using high resolution time-lapse video microscopy, Jacquet et al. examined the translocation of an Msn2-GFP hybrid protein in single cells. Under the bright light of the fluorescence microscope, Msn2 migrates to the nucleus, indicating that light generates a stress response in GFP- expressing cells.
Rather than simply translocating to the nucleus, Msn2 and Msn4 display an unexpected oscillatory pattern in the light-exposed cells, synchronously shuttling into and out of the nucleus with a periodicity of a few minutes. The oscillations only occur at intermediate stress levels; high stress causes Msn2 and Msn4 to remain in the nucleus, whereas at low stress levels the proteins remain in the cytoplasm. The oscillatory behavior varies between individual cells and does not require new protein synthesis.
A computational model of the stress response predicts that one or more additional components make up an autoregulatory loop that primes Msn2 and Msn4 for export from the nucleus. Similar autoregulatory models explain oscillatory phenomena like calcium waves and biological clocks. Because it does not require new protein synthesis, though, the oscillation of Msn2 and Msn4 constitutes a new class of periodic process. The authors are now searching for additional components of the autoregulatory loop in yeast. ▪