Dissecting the temporal dynamics of eukaryotic metabolism in single cells

Our lab has recently discovered metabolic oscillations in single cells of baker’s yeast, where crucial energy compounds show concentration waves with the period of several hours. Evidence suggests that the metabolic oscillations drive the cell through its division cycle, that is, tell the cell when to commit for reproduction and when to split in two cells. In this thesis, we studied what causes the metabolic oscillations in the first place. Since baker’s yeast is a model organism similar to human cells, investigating the nature of the metabolic oscillations controlling the cell division cycle in yeast will eventually help to better understand cancer, a disease with uncontrollably dividing cells. Here, using microscopy and microfluidics, we developed a novel method to measure metabolic activities inside the cell over time. With this method, we discovered that the cell makes different building material in different time periods. For example, at the beginning of the division cycle, the cell makes proteins but no lipids. With an advanced computational modelling, we found that this temporal segregation dramatically changes metabolism, for instance, the cell alters sugar consumption during the division cycle. To describe temporal changes of metabolism better, we established an existing pyruvate sensor in yeast but found it non-functional. Instead, we developed from scratch an RNA-based sensor for another important metabolite, fructose-1,6-bisphosphate. We showed that our sensor also measures the rate of glycolysis, the central biochemical process. Thus, we have found the cause of the metabolic oscillations and developed a novel sensor to study them.