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Dissecting the wiring of yeast's glucose sensing circuit

剖析酵母葡萄糖传感电路的接线

基本信息

批准号：
7476271
负责人：
Jeffrey Sabina
金额：
$ 5.04万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
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/7476271
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

项目摘要

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）：几乎所有的生命都依赖于葡萄糖产生的能量。检测和响应环境中这种普遍存在的单糖的存在的必要性导致了其有效吸收和利用的复杂机制的演变。酵母S.酿酒酵母提供了一个独特的例子，细胞如何响应和代谢这种简单的糖。即使在有氧气的情况下，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。这种偏好并不是因为缺乏氧化中使用的酶，而是因为它们受到葡萄糖的严格调节。这是葡萄糖介导的诱导和抑制基因表达的两条主要途径高度相互关联的结果，每条途径影响另一条途径中效应物的表达或活性。这些跨通路相互作用可以赋予该调节回路反馈和前馈控制，这可以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、代谢产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。了解这两种途径是如何整合的，将使我们对酵母最重要的调节回路之一的了解提高到另一个层次。