Bilateral NSF/BIO-BBSRC: Quantifying cellular signalling by dynamically pulsing transcription factors

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When the environment surronding yeast cells change, the cells usually experience stress. This stress causes a protein to change its location within the cell moving from the cytoplasm to the cell nucleus. Surprisingly, the protein does not change location once but moves in and out of the nucleus multiple times in a pulsatile manner. In our own cells, p53, a tumour supressor protein, behaves in a similar fashion when DNA is damaged. It is not well understood why cells should response to change with proteins that have pulsatile dynamics. Using budding yeast and time-lapse microscopy to follow the behaviour of single cells, we will determine if pulsatile dynamics allow the cell to encode environmental stress into the characteristics of the pulses, with each type of environmental change generating a particular dynamics. To respond to stress, cells produce new proteins, but to match the types of new proteins they produce to the stress they are experiencing, they need to be able to determine the type of stress from the dynamics of the proteins that pulse in response to the stress. Therefore, we will determine the extent to which the dynamics of pulsatile factors can be interpreted by downstream genes to allow protein production to be tailored to the environment. Further, we will ask if mild stress is used by yeast cells as a warning for the imminent occurrence of new stress and if cells can better survive if they use such anticipatory behaviour.