Growth landscape formed by perception and import of glucose in yeast

Abstract

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. This post-genomic era would have us think that elementary problems such as the biochemical control of bacterial growth are essentially solved once all the component parts of the system have been accounted for, yet current quantitative models are notoriously deficient outside very specific conditions. By systematically uncoupling extracellular glucose sensing from glucose transport, Hyun Youk and Alexander van Oudenaarden have now discovered that these two functions control yeast growth independently, sometimes with paradoxical interactions. This approach, reducing a complex metabolic network to one simple phenomenological equation with two main parameters, is reminiscent of methods used in physics and a new step in systems biology. The quantitative description of microbial growth using a few measurable parameters is an important challenge in systems biology. Extracellular glucose sensing and uptake initiate the budding yeast's growth on glucose, but conventional growth models focus almost exclusively on glucose uptake. By uncoupling these two parameters, the interaction between glucose perception and import, rather than their individual actions, is now shown to determine the central features of growth.