LOGIC OF THE YEAST METABOLIC CYCLE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞群落通常会表现出有组织的循环行为。 虽然这种现象在复杂系统中的睡眠-觉醒周期和无数其他生物事件中很明显，但在简单的单细胞真核生物芽殖酵母中也观察到了周期性行为。我们已经开发了一种系统，使酵母在连续培养生长过程中表现出强大的，周期性的呼吸爆发。该项目旨在探索这些周期中的代谢波动。对这些代谢循环的广泛基因表达研究表明，约40%的酵母基因组以周期性方式表达。然而，在代谢循环的不同阶段之间切换的代谢触发因素是未知的。我们正在使用1H和13 C NMR来跟踪这些代谢周期中的细胞内和细胞外代谢物，以评估与基因表达相关的代谢通量。NMR对这些实验至关重要，因为意想不到的代谢物可能是重要的同步和调节信号，并且因为13 C示踪剂研究的整合使我们能够探测特定代谢途径对循环的动力学和贡献。 最终，我们希望阐明酵母代谢循环的众多基因表达程序之间切换的代谢触发因素。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Communities of cells will often display organized cyclic behavior. Although this phenomenon is readily apparent in sleep-wake cycles and innumerable other biological events in complex systems, cyclic behavior has also been observed in the simple, unicellular eukaryote budding yeast. We have developed a system whereby yeast exhibit robust, cyclic bursts of respiration during continuous culture growth. This project is designed to probe the metabolic fluctuations during these cycles. Extensive gene expression studies of these metabolic cycles demonstrated that ~40% of the yeast genome is expressed in a periodic fashion. However, the metabolic triggers for switching between different stages of the metabolic cycle are unknown. We are using 1H and 13C NMR to track intracellular and extracellular metabolites during these metabolic cycles to assess metabolic fluxes in relation to gene expression. NMR is critical to these experiments because unexpected metabolites may be important synchronization and regulatory signals, and because the integration of 13C tracer studies allows us to probe the dynamics and contributions of specific metabolic pathways to the cycle. Ultimately, we hope to elucidate the metabolic triggers for switching between the numerous gene expression programs of the yeast metabolic cycle.