Dissecting the wiring of yeast's glucose sensing circuit

Washington University, Saint Louis MO

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Nearly all life depends on energy derived from glucose. The necessity to detect and respond to the presence of this ubiquitous monosaccharide in the environment has resulted in the evolution of sophisticated mechanisms for its efficient uptake and utilization. The yeast S. cerevisiae provides a unique example of how cells respond to and metabolize this simple sugar. This yeast prefers to ferment glucose even in the presence of oxygen, a trait that it shares with certain tumor cells, even though oxidation would yield far more energy. This preference is not due to the absence of the enzymes used in oxidation, but to their stringent regulation by glucose. This is the result of two major pathways for glucose-mediated induction and repression of gene expression that are highly interconnected, with each pathway influencing the expression or activity of effectors in the other. These cross-pathway interactions may endow this regulatory circuit with both feedback and feedforward controls that may give the system the ability to respond rapidly and dynamically to changing levels of glucose. By disrupting and rewiring these control circuits their contributions to the overall system will be measured by monitoring gene regulation, metabolite production, and the selective advantage of an intact network in competitive growth experiments. Understanding how these two pathways are integrated will add another level to our knowledge of one of yeast's most important regulatory circuits. [unreadable] [unreadable] [unreadable]