Dissecting the wiring of yeast's glucose sensing circuit

剖析酵母葡萄糖传感电路的接线

• 批准号: 7271369
• 负责人: Jeffrey Sabina
• 金额: $ 4.88万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7271369
• 关键词: Affect; Asses; Blood; Cause of Death; Cell membrane; Cells; Condition; Country; Detection; Disease Progression; Disruption; Environment; Enzymes; Equilibrium; Evolution; Face; Fasting; Feedback; Fellowship; Gene Expression; Gene Expression Regulation; Genes; Glucose; Glucose Transporter; Goals; Growth; Health; Human; Impairment; Individual; Kinetics; Knock-out; Knowledge; Life; Life Style; Mammals; Measures; Mediating; Modeling; Monitor; Monosaccharides; Names; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Nutrient; Organism; Output; Oxygen; Pathway interactions; Personal Satisfaction; Play; Process; Production; Protein Kinase; Proteins; Regulation; Repression; Role; Saccharomyces; Saccharomyces cerevisiae; Signal Pathway; Signal Transduction; Speed; Stream; System; Testing; Time; Trees; Upper arm; Yeasts; blood glucose regulation; cancer cell; feeding; glucose metabolism; glucose output; glucose sensor; glucose uptake; neoplastic cell; oxidation; preference; research study; response; sugar; trait; transcription factor; uptake

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.

描述（由申请人提供）：几乎所有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来说明细胞如何响应和代谢这种单糖。这种酵母即使在有氧的情况下也更喜欢发酵葡萄糖，这是它与某些肿瘤细胞共有的特性，尽管氧化会产生更多的能量。这种偏好并不是因为缺乏用于氧化的酶，而是因为它们受到葡萄糖的严格调节。这是葡萄糖介导的基因表达诱导和抑制的两条主要途径的结果，这两条途径高度相互关联，每条途径都会影响另一条途径中效应子的表达或活性。这些跨通路相互作用可以赋予该调节电路反馈和前馈控制，从而使系统能够快速、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、代谢物产生以及竞争性生长实验中完整网络的选择性优势来测量。了解这两条途径如何整合将使我们对酵母最重要的调节回路之一的了解更上一层楼。