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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM076967-03
Application #
7476271
Study Section
Special Emphasis Panel (ZRG1-F08-G (20))
Program Officer
Haynes, Susan R
Project Start
2006-08-01
Project End
2009-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
3
Fiscal Year
2008
Total Cost
$50,428
Indirect Cost
Name
Washington University
Department
Genetics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Kuttykrishnan, Sooraj; Sabina, Jeffrey; Langton, Laura L et al. (2010) A quantitative model of glucose signaling in yeast reveals an incoherent feed forward loop leading to a specific, transient pulse of transcription. Proc Natl Acad Sci U S A 107:16743-8
Sabina, Jeffrey; Brown, Victoria (2009) Glucose sensing network in Candida albicans: a sweet spot for fungal morphogenesis. Eukaryot Cell 8:1314-20
Sabina, Jeffrey; Johnston, Mark (2009) Asymmetric signal transduction through paralogs that comprise a genetic switch for sugar sensing in Saccharomyces cerevisiae. J Biol Chem 284:29635-43
Brown, Victoria; Sabina, Jeffrey; Johnston, Mark (2009) Specialized sugar sensing in diverse fungi. Curr Biol 19:436-41