Date of Award


Degree Type


Degree Name


Degree Program

Integrative Biology


Biological Sciences

Major Professor

Zhengchang Liu

Second Advisor

Mary Clancy

Third Advisor

Wendy Schluchter

Fourth Advisor

Bernard Rees


The budding yeast Saccharomyces cerevisiae is a pioneering model organism for studies on the regulation of eukaryotic metabolism. Yeast cells can import and metabolize a variety of carbon and nitrogen compounds and possess complex and overlapping regulatory networks to coordinate responses to nutrient availability. Metabolic control is exerted at transcriptional and translational levels through large-scale changes in gene expression and through allosteric regulation of enzymes in key pathways. These pathways are regulated upstream by nutrient sensing kinases, which play important roles in growth control and development. The focus of this dissertation is on the characterization of the functions of a major nutrient sensing kinase, Sch9.

Deletion of SCH9 causes the rapid accumulation of spontaneous suppressor mutations, which skew observations of sch9D phenotypes. I isolated recessive sch9D suppressor mutants in two commonly used laboratory strain backgrounds and show that all carried mutations in either IRA1 or IRA2. Suppressor mutations in ira1 and ira2 reverse several phenotypes in sch9D strains, including the induction of HAP4 expression and the inability to grow on non-fermentable carbon sources. Mutations in genes that lead to activation of the Protein Kinase A (PKA) pathway also suppress sch9D mutant phenotypes.

RNA-sequencing analysis of wild type versus sch9D mutant strains suggests that Sch9 has a role in regulating the expression of genes in mitochondrial biogenesis, nitrogen catabolite repression (NCR), phosphate metabolism, and purine biosynthesis as well as the expression of ribosomal protein-encoding genes, tRNAs, and small nuclear RNAs. Using genetic and molecular techniques, I was able to experimentally validate a role for Sch9 in regulating NCR-responsive gene expression.

To further investigate the connection between Sch9 and the NCR pathway, I investigated a potential interaction with the transcriptional activator, GLN3. Deletion of GLN3 leads to glutamine starvation and, consequently, mitochondrial DNA (mtDNA) loss. gln3D mutant strains also exhibit adenine-induced cell lethality, which can be suppressed by loss of mitochondrial DNA and deletion of SCH9. I propose that decreased flux through the purine nucleotide biosynthesis pathway, either due to an sch9D mutation or loss of mtDNA, reduces glutamine consumption and prevents adenine toxicity in gln3D mutants.


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Available for download on Thursday, August 05, 2027