The cell division cycle - the process by which two daughter cells are generated from an initial mother cell - is fundamental for the continuation of life, and its dysregulation is linked to disease. Because cell division is energetically and biosynthetically a highly demanding process, cells need to carefully decide when to pursue the execution of their cell division program. Recent findings showed that several phenotypic aspects of microbial cells can be shaped by metabolic rates, or otherwise, fluxes, independently of the extracellular nutrient conditions. These findings inspired the hypothesis that the commitment of budding yeast cells to the cell division cycle is a decision that depends on metabolic flux. Combining single-cell and population-level approaches, it was found that the rate of glycolysis could dictate whether yeast cells commit to the cell division cycle or abstain from it, independently of extracellular glucose availability. Further, it was found that apart from the commitment to the cell division program, metabolic rates are also important for its execution. Specifically, it was found that while DNA replication is majorly insensitive to the rate of glycolysis, the process of bud formation requires a sufficiently high glycolytic rate for its unimpeded progression. Finally, in the quest of the mechanistic link between metabolic rate and cell cycle activation, it was found that the rate of protein synthesis, which is highly dynamic, peaks right before cell cycle commitment, causing an increase in the concentration of a critical upstream cell cycle activator.
|Translated title of the contribution||Metabolic-rate dependent cell cycle entry and progression in Saccharomyces cerevisiae|
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2017|