Date of Graduation

12-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Cell & Molecular Biology (PhD)

Degree Level

Graduate

Department

Cell & Molecular Biology

Advisor/Mentor

Lewis, Jeffrey A.

Committee Member

Du, Yuchun

Second Committee Member

Adams, Paul D.

Third Committee Member

Lessner, Daniel J.

Keywords

Acetylation; Acetylome; Global; Heat shock; Stress; Yeast

Abstract

All organisms face a constant barrage of environmental stresses. Single-cell organisms such as Saccharomyces cerevisiae, or common Baker’s yeast, must rely solely on cellular responses in order to survive. This response must occur in a rapid and highly coordinated manner to quickly inhibit all unnecessary processes and shuttle all available resources to those necessary for survival. One method that cells utilize for rapid protein regulation is the use of post-translational modifications. Enzymes within the cell add or remove a variety of chemical modifications, thus altering the local chemical environment of a protein. This creates a conformational change in the protein that can increase, decrease, or completely change the activity of the protein, as well as target them for relocation or degradation. Examples of common post-translational modifications include phosphorylation, ubiquitination, and the focus of this dissertation, acetylation.

That protein acetylation occurs has been known for decades, but it is only recently that advances in technology such as high-resolution mass spectrometry and immunoprecipitation have led to the recognition of thousands of acetylated proteins across all domains of life. The roles and regulation of this modification, however, are still widely unknown. One approach to better understand possible roles for acetylation is to look at its dynamics in response to environmental stress. In this dissertation, I examine global changes in protein acetylation in the response of Saccharomyces cerevisiae to a mild heat shock and the potential mechanisms regulating these changes.

Following an introductory literature review, this dissertation will cover the results of a large time-scale profiling of acetylome dynamics in response to heat shock. Proteins identified in this experiment are enriched for many cellular processes, suggesting that acetylation may play a much wider regulatory role than previously believed. These proteins are also enriched for interactions with many lysine acetyltransferases and deacetylases, suggesting that the regulation of this modification is complex. The next chapter will then discuss possible mechanisms regulating this response. This includes the investigation into concentrations of metabolites known to affect acetylation and deacetylation, lysine acetyltransferase and deacetylase complex remodeling, and localization changes for those complexes within the cell.

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