LOGIC OF THE YEAST METABOLIC CYCLE

点击翻译按钮获取中文摘要

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.