Defense Date

2022

Document Type

Thesis

Degree Name

Master of Science

Department

Biology

First Advisor

Dr. Alaattin Kaya

Abstract

The Mechanistic Target of Rapamycin (mTOR) is an evolutionarily conserved kinase that regulates diverse cellular processes in response to nutritional and other environmental cues and various forms of stress. The genetic and pharmacological modulation of the mTOR activity has shown to be a promising intervention for longevity in diverse models, from yeast to primates. In addition, mTOR signaling is deregulated in common diseases like cancer, neurodegeneration, and diabetes. It is important to characterize the additional components of the mTOR regulatory network, including both mTORC1 and mTORC2 targets, to provide a potential therapeutic target to regulate TOR activity. Here, we utilized a genome-wide dosage sensitivity screen to identify additional interactors of mTORC1 in yeast. Our findings identified highly conserved and previously unknown genetic components of the mTOR regulatory network with diverse biological functions. Of the top candidates, two paralogous genes, ARF1 and ARF2 presented in the top three slowest doubling times for growth when their dosage increased in the absence of TOR1. This study focused on characterizing the ARF1 and ARF2 genes’ functions within the mTOR pathway. Although further studies are needed to directly describe their function in mTOR-dependent cellular processes, our initial characterization of their role in mTOR-dependent lifespan extension validated both ARF1 and ARF2 as a modulator of aging. Because mTOR-dependent pathways and the ARF1 and ARF2 genes are highly conserved across many different phylogenies, including humans, the lifespan regulating roles of these genes might serve as an aging and disease intervention in the future.

Rights

Samantha McLean © The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

7-22-2022

Available for download on Wednesday, July 21, 2027

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