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

当酵母细胞周围的环境发生变化时，细胞通常会经历压力。这种压力导致蛋白质改变其在细胞内的位置，从细胞质转移到细胞核。令人惊讶的是，这种蛋白质不会改变一次位置，而是以脉动的方式多次进出细胞核。在我们自己的细胞中，当DNA受损时，p53，一种肿瘤抑制蛋白，也会以类似的方式表现出来。目前还不清楚为什么细胞会对具有脉动动力学的蛋白质的变化作出反应。使用出芽酵母和延时显微镜来跟踪单个细胞的行为，我们将确定脉冲动力学是否允许细胞将环境压力编码为脉冲的特征，每种类型的环境变化都会产生特定的动力学。为了应对压力，细胞会产生新的蛋白质，但为了使它们产生的新蛋白质的类型与它们所经历的压力相匹配，它们需要能够根据蛋白质对压力的反应动态来确定压力的类型。因此，我们将确定在多大程度上脉动因子的动态可以被下游基因解释，以允许蛋白质生产适应环境。此外，我们将询问酵母细胞是否使用温和的压力作为即将发生的新压力的警告，如果细胞使用这种预期行为，它们是否可以更好地生存。

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.