Date Approved

1-30-2018

Embargo Period

2-1-2019

Document Type

Thesis

Degree Name

M.S. Bioinformatics

Department

Molecular and Cellular Biosciences

College

College of Science & Mathematics

First Advisor

Hickman, Mark J.

Second Advisor

Carone, Benjamin

Third Advisor

Malamon, John

Subject(s)

Gene expression; Oxygen--Physiological effect

Disciplines

Bioinformatics

Abstract

All organisms appear to have the ability to sense and respond to changes in their environment. Hypoxia, or low oxygen, is experienced by many organisms at some point in their life cycle. Some organisms such as S. cerevisiae, a species of yeast, respond by dramatically altering gene expression. The result is that genes needed in the new environment are turned on and unneeded genes are turned off. S. cerevisiae has been used in our study because it shares many genes with other eukaryotes, including humans, so many of our findings are applicable to these organisms. Here, we tried to understand how metabolic genes change gene expression during the transition to hypoxia. Many metabolic pathways, such as the electron transport chain, depend upon oxygen and therefore likely respond to changes in oxygen levels. In order to study this, we followed gene expression over four hours as cells transitioned from normoxia to hypoxia. We performed this time course in triplicate and overlaid the expression data onto metabolic pathways in order to uniquely visualize the changes over time and across many pathways.

As expected, we found widespread changes in many oxygen-dependent metabolic pathways, such as aerobic respiration and ergosterol biosynthesis. In addition, we found changes in pathways not known to be associated with oxygen, suggesting that oxygen is linked to many aspects of metabolism. Next, we tried to understand the transcriptional regulation of the metabolic genes by searching for transcription factor binding sites and signaling pathways that are enriched in clusters of oxygen-regulated genes. We were able to link known signaling pathways, like the Hap1 and other hypoxia signaling pathways, to control of metabolic genes. Taken together, our work uses novel approaches to show how metabolic pathways change in response to the environment and to identify signaling pathways that mediate this response.

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