Project description:Perturbation of the gated-synchrony system in yeast with phenelzine, an antidepressant drug used in the treatment of affective disorders in humans, leads to a rapid lengthening in the period of the genome-wide transcriptional oscillation. The effect is a concerted, genome-scale change in expression that is first seen in genes maximally expressed in the late-reductive phase of the cycle, doubling the length of the reductive phase within two cycles after treatment. Clustering of genes based on their temporal patterns of expression yielded just three super clusters whose trajectories through time could then be mapped into a simple 3D figure. In contrast to transcripts in the late-reductive phase, most transcripts do not show transients in expression relative to others in their temporal cluster but change their period in a concerted fashion. Mapping the trajectories of the transcripts into low-dimensional surfaces that can be represented by simple systems of differential equations provides a readily testable model of the dynamic architecture of phenotype. In this system, period doubling may be a preferred pathway for phenotypic change. As a practical matter, low-amplitude, genome-wide oscillations, a ubiquitous but often unrecognized attribute of phenotype, could be a source of seemingly intractable biological noise in microarray studies. Experiment Overall Design: Phenelzine was added to the system after the first cycle to induce period doubling
Project description:Perturbation of the gated-synchrony system in yeast with phenelzine, an antidepressant drug used in the treatment of affective disorders in humans, leads to a rapid lengthening in the period of the genome-wide transcriptional oscillation. The effect is a concerted, genome-scale change in expression that is first seen in genes maximally expressed in the late-reductive phase of the cycle, doubling the length of the reductive phase within two cycles after treatment. Clustering of genes based on their temporal patterns of expression yielded just three super clusters whose trajectories through time could then be mapped into a simple 3D figure. In contrast to transcripts in the late-reductive phase, most transcripts do not show transients in expression relative to others in their temporal cluster but change their period in a concerted fashion. Mapping the trajectories of the transcripts into low-dimensional surfaces that can be represented by simple systems of differential equations provides a readily testable model of the dynamic architecture of phenotype. In this system, period doubling may be a preferred pathway for phenotypic change. As a practical matter, low-amplitude, genome-wide oscillations, a ubiquitous but often unrecognized attribute of phenotype, could be a source of seemingly intractable biological noise in microarray studies. Keywords: Time Course Experiment
Project description:To investigate the glucose regulatory system in Saccharomyces cerevisiae, we conducted a time-course in which glucose-depleted wildtype (WT) cells were inoculated into fresh media (SC, 2% glucose). Their subsequent transcriptional output was monitored over a period of five hours by DNA microarrays: samples for gene expression profiling were taken immediately after, as well as 3, 7.5, 15, 30, 60, 110, 150, and 300 minutes after inoculation into fresh medium. Transcripts upregulated are involved in translational processes such as the GO biological processes “ribosome biogenesis” and “ribosome localization”. Transcripts downregulated are enriched for the GO biological processes “cellular respiration” and various metabolism related processes. The time-course was used to verify the physiological relevance of gene expression profiles determined for individual deletions of glucose regulatory system components. Importantly, transcripts up- or downregulated in WT cells upon the addition of glucose are similarly up- or downregulated in deletion mutants that each lack a component of the glucose regulatory system.