Understanding the regulation of glucose sensing and transport in budding yeast using dynamic inputs

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Glucose is the preferred source of energy for nearly all cells, from microbes to plants to animals, but we do not understand how cells sense and respond to changes in glucose's availability. We propose to study the sensing and uptake of glucose in budding yeast, one of the simplest organisms that has a similar structure to our own cells. Yeast has seven main transporters for glucose, and our focus is to understand why so many are necessary and how only the appropriate transporters are present at the appropriate time. To do so, we will study both populations of and individual cells and probe their behaviour in fluctuating levels of glucose to determine if particular transporters increase in number in response to either the concentration of extracellular glucose or to how that extracellular concentration changes with time. We will thus determine under which conditions each transporter is optimum and has its highest levels. Further, using mutations to disrupt sensing and mathematical modelling of our results, we will discover how the underlying biochemistry works to ensure a suitable rate of uptake of glucose through changing the types of transporters present. Our results will both address the fundamental question of how cells can regulate their import of glucose and provide quantitative measurements of the levels of the transporters that can be exploited by the biotechnology industry to, for example, increase production of valuable biological compounds.