Project Director

Ferdoush, Jannatul

Department Examiner

Sharma, Ritu; Giles, David K.

Department

Dept. of Biological and Environmental Sciences

Publisher

University of Tennessee at Chattanooga

Place of Publication

Chattanooga (Tenn.)

Abstract

Transcription factors (TFs) function as precision switches that integrate signaling inputs, chromatin state, and protein homeostasis to control gene expression. This thesis unites three interconnected research themes: (1) mechanistic studies of the ubiquitin-proteasome system (UPS) in regulating eukaryotic TFs, focusing on polymerase-associated Factor 1 (Paf1) and TATA-box binding protein-associated factor 2 (Taf2); (2) identification of biomarker genes within odor-related TF networks; and (3) integration of published undergraduate research linking molecular regulation, bioinformatics, and synthetic biology. These themes are purposefully structured so that mechanistic insight into TF control sets up network-level discovery and, in turn, motivates applied and translational directions. In Part 1, we examined the UPS-mediated regulation of Paf1 and Taf2. While UPS is known to control their stability, its precise mechanisms and transcriptional dependency were unclear. Our results showed that Paf1 abundance remains unchanged upon α-amanitin-induced transcriptional inhibition, suggesting that UPS regulation may occur independently of transcription and may reflect protein quality control rather than transcription-coupled degradation. Having established transcription-independent UPS effects on Paf1, we next asked whether a parallel, ligase-specific mechanism might govern Taf2. For Taf2, we screened 30 of 60 known yeast E3 ligases but did not identify a specific ligase, indicating the need for broader screening to pinpoint its regulator. Building on these mechanistic findings, we moved from protein-level regulation to system-level patterns by interrogating TF-centered networks computationally. In Part 2, we used computational approaches to identify biomarker genes within odor-related TF networks. Through Gene Expression Omnibus (GEO) dataset analysis, Adenylate Cyclase 3 (ADCY3) emerged as a key dysregulated olfactory-related gene in kidney and colorectal cancers. Functional pathway analysis revealed that ADCY3 modulates tumor progression through cyclic adenosine monophosphate (cAMP) signaling via protein kinase A (PKA), exchange protein directly activated by cAMP (EPAC), and cAMP response element–binding protein (CREB) pathways, highlighting its potential as a potential therapeutic target. The identification of ADCY3-linked signaling as a candidate driver of phenotype provided a natural bridge to integrative, application-oriented studies. Part 3 synthesizes findings from three of our recent publications, demonstrating the integration of molecular and bioinformatics strategies to address biomedical and environmental challenges. The first study identified TOP2A as a prognostic biomarker and a compound from Andrographis paniculata as a promising therapeutic candidate for kidney and liver cancers. The second study examined farnesoid X receptor (FXR) agonists in regulating kinase pathways in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), emphasizing their therapeutic significance. The third introduced PlastiCRISPR, a CRISPR-based system enabling microbial plastic degradation, showcasing the potential of genome editing for environmental applications. Together, these studies provide a cohesive framework for dissecting transcription factor regulation and translating molecular signatures into actionable biomarkers, bridging fundamental molecular biology with applied biomedical and environmental research.

Acknowledgments

I am deeply grateful to Dr. Jannatul Ferdoush for her mentorship and steady guidance. I also thank my committee members, Dr. David Giles and Dr. Ritu Sharma, for their time and thoughtful feedback that strengthened both the experiments and the writing. I appreciate the UTC BGE Department for a supportive environment and for access to facilities and resources that made this work possible. First and foremost, this thesis could not have been written without generous collaboration. I thank Sam Smith and Quin Goodson for their partnership in unearthing ADCY3 as a key olfaction-related biomarker gene and potential therapeutic target in kidney and colorectal cancers-their insights, discussions, and detailed figure reviews greatly strengthened the work at hand. I am also very appreciative of my peers for providing unpublished notes and for their assistance in troubleshooting experiments. I also thank all the co-authors of the three published papers. Lastly, to my family and friends, thank you for your patience, encouragement, and constant support.

Degree

B. S.; An honors thesis submitted to the faculty of the University of Tennessee at Chattanooga in partial fulfillment of the requirements of the degree of Bachelor of Science.

Date

12-2025

Subject

Eukaryotic cells--Genetics; Gene expression; Small ubiquitin-related modifiers; Transcription factors; Ubiquitin

Keyword

Molecular Biology; Transcription; Gene expression

Discipline

Molecular Biology

Document Type

Theses

Extent

i, 52 leaves

DCMI Type

Text

Language

English

Rights

http://rightsstatements.org/vocab/InC/1.0/

License

http://creativecommons.org/licenses/by-nc-nd/4.0/

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