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Date of Award

Summer 2024

Document Type

Masters Thesis (Campus-Only Access)

Department or Program Affiliation

Biology

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Wang, Adrienne M.

Second Advisor

Dahlberg, Lina

Third Advisor

Galati, Nick

Abstract

Mitochondrial function and innate immune-mediated inflammation are two important factors influencing healthy aging and lifespan. Innate immune mediated increases in inflammation have been implicated in aging and neurodegenerative disease pathogenesis. Recent literature points to how dysfunctional mitochondria might act as a signaling hub for the innate immune system. In this study, we present a novel Drosophila fly model which conditionally expresses the UL12.5 nuclease which is targeted to the mitochondria and degrades mtDNA. Findings from the Wang lab show that UL12.5-mediated mtDNA depletion is sufficient to increase innate immune signaling through innate immune signaling pathways. This fly effectively links mitochondrial dysfunction and innate immune signaling, providing a basis with which we can increase our understanding of the role of mitochondrial stress and innate immunity with age, and how this signaling changes resistance to bacterial challenge.

We injected flies with gram negative bacteria and measured survival of flies following injection at three different time points: young age (3 day), middle age (10 day) and old age (20 day). Our results indicate the upregulated innate immune signaling seen in UL12.5-expressing flies significantly increases median survival after injection with E. coli, compared to control fly strains (P < 0.05). Our findings also indicate a trend where old-age decreases resistance to injection compared to young-age, though this trend did not yet meet statistical significance (P > 0.05).

Type

Text

Publisher

Western Washington University

OCLC Number

1456644337

Subject – LCSH

Mitochondrial DNA; Drosophila; Natural immunity; Immune response

Format

application/pdf

Genre/Form

masters theses

Language

English

Rights

Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this document for commercial purposes, or for financial gain, shall not be allowed without the author’s written permission.

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