Graduation Date

5-2017

Document Type

Master's Thesis

Degree Name

Master of Science

Department or Program

Biological Sciences

Department or Program Chair

Maggie Louie, PhD

First Reader

Pankah Kapahi, PhD

Second Reader

Kristylea Ojeda, PhD

Abstract

The field of medicine research is embroiled in a battle against aging. Particular focus is on the extension of lifespan and health-span. Lifespan duration is affected by many factors, one of which is the maintenance of the intestines of the organism. Homeostasis of the intestines is controlled by the regulation of intestine cell apoptosis and intestine cell proliferation. My research explores the role of two protein subunits found in a complex which may have possible functions in the regulation of these processes. The overall complex is formed from six subunit proteins, some of which are known to assist in other cellular functions including cytoskeleton assembly, proteostasis, gene regulation, and DNA repair. However, the role these subunits play in maintaining intestinal homeostasis is currently unknown. Nor is it known if the expression of these proteins varies in different cell types. My hypothesis was that loss of these subunits would increase intestinal permeability, resulting in a loss of longevity. Downregulation of these these subunits would result in novel activation of established pathways to increase permeability. The model organism, Drosophila melanogaster (fruit fly), has complex anatomical, physiological, and behavioral characteristics, a relatively short lifespan, established intestinal stem cell lineage, and powerful genetic tools that allow the rapid understanding of the function of these subunits in the gut. My results show that gut-specific Down Regulation of the proteins increases gut permeability, negatively changes intestinal stem cell proliferation, and regulates longevity in the model organism Drosophila melanogaster. My results further elucidate the nature of proteins’ effects on the extension or abrogation of lifespan, and contribute to research on these proteins in complex organisms.

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