Systems Level Studies of Nutrient Homeostasis

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Systems Level Studies of Nutrient Homeostasis

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Title: Systems Level Studies of Nutrient Homeostasis
Author: Rizvi, Abbas
Citation: Rizvi, Abbas. 2011. Systems Level Studies of Nutrient Homeostasis. Doctoral dissertation, Harvard University.
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Abstract: In conditions of phosphate deprivation, the budding yeast, Saccharomyces cerevisiae activates the phosphate starvation response pathway (PHO pathway). Induction of the PHO pathway causes the transcription of genes involved with phosphate metabolism. Phosphate transport genes are activated during starvation, giving rise to the presence of Pho84, the high affinity transporter. In high phosphate conditions low affinity transporters reside at the plasma membrane. Here we show that Spl2, a suppressor of phospholipase-C, is involved in the down-regulation of the low affinity transport system. This phenomenon gives rise to complex population dynamics and bistability. Furthermore, we demonstrate how the phenotype of strains lacking Pho84 can be explained in context of unconstrained positive feedback through Spl2. We then turn our attention towards comparative studies of the PHO pathway, comparing the transcriptional response of S. cerevisiae to C. glabrata. Using expression microarrays and deep sequencing, we find that the transcriptional circuit in C. glabrata has been altered such that transcriptional cooperativity is lost, nucleosome positioning is altered, and transcriptional competition between the transcription factor Pho4 and centromere binding factor, Cbf1, is relatively conserved.
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