An important challenge in systems biology is to quantitatively describe microbial growth using a few measurable parameters that capture the essence of this complex phenomenon. Two key events at the cell membrane—extracellular glucose sensing and uptake—initiate the budding yeast’s growth on glucose. However, conventional growth models focus almost exclusively on glucose uptake. Here we present results from growth-rate experiments that cannot be explained by focusing on glucose uptake alone. By imposing a glucose uptake rate independent of the sensed extracellular glucose level, we show that despite increasing both the sensed glucose concentration and uptake rate, the cell’s growth rate can decrease or even approach zero. We resolve this puzzle by showing that the interaction between glucose perception and import, not their individual actions, determines the central features of growth, and characterize this interaction using a quantitative model. Disrupting this interaction by knocking out two key glucose sensors significantly changes the cell’s growth rate, yet uptake rates are unchanged. This is due to a decrease in burden that glucose perception places on the cells. Our work shows that glucose perception and import are separate and pivotal modules of yeast growth, the interaction of which can be precisely tuned and measured.
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We thank E. Boles for the kind gift of strains. We also thank D. Botstein, D. Muzzey, J. Gore and S. Rifkin for critical reading of our manuscript and useful discussions. This work was funded by a National Institutes of Health (NIH) Director’s Pioneer awarded to A.v.O., and grants from the NIH and National Science Foundation (NSF). H.Y. was supported by the Natural Sciences and Engineering Research Council of Canada’s (NSERC) Graduate Fellowship.
Author Contributions H.Y. performed the experiments. H.Y. and A.v.O. designed experiments, analysed data and wrote the manuscript.
The authors declare no competing financial interests.
This file contains a Supplementary Discussion, Supplementary Figures 1-17 with Legends, Supplementary References and a Supplementary Chart of the Strains used in this study. (PDF 4418 kb)
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Youk, H., van Oudenaarden, A. Growth landscape formed by perception and import of glucose in yeast. Nature 462, 875–879 (2009). https://doi.org/10.1038/nature08653
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