A mathematical and experimental study of feedback in the single-cell dynamics of a transcriptional network in budding yeast

细胞通过它们用来感知环境的生化网络的相应变化来对环境变化做出反应。这些网络是复杂的，被激活的基因经常反馈影响首先激活基因的蛋白质的水平。通过研究单细胞生物芽殖酵母如何对细胞外糖的变化做出反应，我们将确定在控制糖感测的遗传网络中发生的三种反馈的作用。使用微流体技术和荧光蛋白，我们将量化单个酵母细胞对糖水平以我们可以定义的方式波动的环境的反应。通过对细胞进行基因工程改造，我们可以通过提供化学物质来设定每种反馈的水平，我们将确定当反馈发生变化时，细胞对波动信号的反应如何变化。我们将使用数学模型来预测最具信息量的信号，以发现反馈如何决定细胞的反应。除了对具有工业价值的生物体中营养感测的见解外，我们的研究也很重要，因为它将开发实验和数学技术来研究活细胞中生化网络的动态响应。所有的细胞，无论是在我们自己的身体还是单个细菌中，都是在波动的环境中进化的，在这种环境中，动态反应往往与通常研究的长期行为一样相关。

Cells respond to environmental changes through corresponding changes in the biochemical networks they use to sense the environment. These networks are complex with genes that are activated often feeding back to affect levels of the proteins that first activated the genes. By studying how the single-celled organism, budding yeast, responds to changes in extracellular sugars we will determine the role of three of these feedbacks that occur in the genetic network that controls sensing of sugar. Using microfluidic technology and fluorescent proteins, we will quantify the responses of individual yeast cells to environments whose sugar levels fluctuate in ways we can define. By genetically engineering the cells so that we can set the level of each of the feedbacks by a chemical we supply, we will determine how the cell's response to fluctuating signals changes when the feedback changes. We will use mathematical modelling to predict the most informative signals to apply to discover how feedback determines the cell's response. In addition to its insights into nutrient sensing in an industrially valuable organism, our study is important because it will develop experimental and mathematical techniques to study the dynamic response of a biochemical network in living cells. All cells, whether in our own bodies or a single bacterium, have evolved in fluctuating environments where dynamic responses are often just as relevant as the long-term behaviours commonly studied.