Dissecting the wiring of yeast's glucose sensing circuit

描述（由申请人提供）：几乎所有的生命都依赖于来自葡萄糖的能量。检测和响应环境中这种普遍存在的单糖的必要性导致了其有效吸收和利用的复杂机制的发展。酿酒酵母提供了一个独特的例子，说明细胞如何对这种单糖作出反应和代谢。即使有氧气存在，这种酵母也更喜欢发酵葡萄糖，这是它与某些肿瘤细胞共有的特征，尽管氧化会产生更多的能量。这种偏好不是由于缺乏用于氧化的酶，而是由于它们受到葡萄糖的严格调节。这是葡萄糖介导的诱导和抑制基因表达的两种主要途径的结果，这两种途径高度相互关联，每一种途径都影响另一种途径中效应物的表达或活性。这些交叉通路的相互作用可能赋予这个调节回路反馈和前馈控制，这可能使系统能够快速和动态地响应葡萄糖水平的变化。通过破坏和重新连接这些控制电路，它们对整个系统的贡献将通过监测基因调控、代谢物产生和竞争性生长实验中完整网络的选择优势来衡量。了解这两种途径是如何整合的，将为我们对酵母最重要的调节回路之一的了解增加另一个层次。

DESCRIPTION (provided by applicant): Nearly all life depends on energy derived from glucose. The necessity to detect and respond to the presence of this ubiquitous monosaccharide in the environment has resulted in the evolution of sophisticated mechanisms for its efficient uptake and utilization. The yeast S. cerevisiae provides a unique example of how cells respond to and metabolize this simple sugar. This yeast prefers to ferment glucose even in the presence of oxygen, a trait that it shares with certain tumor cells, even though oxidation would yield far more energy. This preference is not due to the absence of the enzymes used in oxidation, but to their stringent regulation by glucose. This is the result of two major pathways for glucose-mediated induction and repression of gene expression that are highly interconnected, with each pathway influencing the expression or activity of effectors in the other. These cross-pathway interactions may endow this regulatory circuit with both feedback and feedforward controls that may give the system the ability to respond rapidly and dynamically to changing levels of glucose. By disrupting and rewiring these control circuits their contributions to the overall system will be measured by monitoring gene regulation, metabolite production, and the selective advantage of an intact network in competitive growth experiments. Understanding how these two pathways are integrated will add another level to our knowledge of one of yeast's most important regulatory circuits.