Coupling of the Yeast Metabolic Cycle and the Cell Division Cycle in Populations and Single Cells

Biological oscillators are ubiquitous in living systems. They allow cellular processes to anticipate and act in synchrony with regular events in the outside world (such as the day/night cycle), or they ensure that processes occur in a particular order. Living things typically contain multiple oscillators, which can often couple to each other and influence each other's timing and function. The purpose of this thesis has been to investigate the relationship between two coupled oscillators in \textit{Saccharomyces cerevisiae}: the yeast metabolic cycle and the cell division cycle. I have focused on two key questions: what is the biological significance of their coupling, and is one oscillator dominant in its interaction with the other?

First, I investigated the temporal relationship between the cell division cycle and metabolic shifts that occur during the metabolic cycle across diverse yeast strains. I showed that a particular cell cycle event (DNA replication) was consistently delayed relative to a metabolic event (entry into the high oxygen consumption phase). This suggested that an earlier cell cycle event (Start and commitment to the cell cycle) was tied to the onset of high oxygen consumption. Second, I used fluorescent probes to examine the relationship between the metabolic cycle and the commitment to cell cycle progression at single-cell resolution. This revealed that cells enter high oxygen consumption phase of the metabolic cycle before passing Start, supporting a model of metabolic cycle/cell division cycle coupling in which the shorter metabolic cycle controls cell cycle commitment, likely via modulation of cell size thresholds.