Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature. 2009 Dec 17;462(7275):875-9. doi: 10.1038/nature08653.
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.
系统生物学的一个重要挑战是使用少数可测量的参数来定量描述微生物的生长,这些参数能够捕捉到这一复杂现象的本质。细胞膜外葡萄糖感应和摄取这两个关键事件启动了酵母在葡萄糖上的生长。然而,传统的生长模型几乎完全专注于葡萄糖摄取。在这里,我们展示了仅关注葡萄糖摄取无法解释的生长速率实验结果。通过施加与感应到的细胞外葡萄糖水平无关的葡萄糖摄取速率,我们表明,尽管增加了感应葡萄糖浓度和摄取速率,细胞的生长速率仍可能降低甚至接近零。我们通过显示葡萄糖感知和导入之间的相互作用,而不是它们各自的作用,决定了生长的核心特征,并使用定量模型来描述这种相互作用,解决了这个难题。通过敲除两个关键葡萄糖传感器来破坏这种相互作用,会显著改变细胞的生长速率,而摄取速率则保持不变。这是由于葡萄糖感知对细胞造成的负担减轻了。我们的工作表明,葡萄糖感知和导入是酵母生长的独立且关键的模块,它们的相互作用可以被精确地调整和测量。