GSBS Dissertations and Theses

Approval Date

5-15-2015

Document Type

Doctoral Dissertation

Academic Program

Interdisciplinary Graduate Program

Department

Medicine

First Thesis Advisor

Neal Silverman, PhD

Keywords

Drosophila, Drosophila Proteins, Innate Immunity, Post-Translational Protein Processing, Proteolysis, Signal Transduction, Ubiquitin

Subjects

Dissertations, UMMS; Drosophila; Drosophila Proteins; Immunity, Innate; Protein Processing, Post-Translational; Proteolysis; Signal Transduction; Ubiquitin

Abstract

Innate immunity is the first line of defense against invading pathogens. It provides immediate protection by initiating both cellular and humoral immune reactions in response to a wide range of infections. It is also important to the development of long-lasting and pathogen-specific adaptive immunity. Thus, studying of the innate immunity, especially the pathogen recognition and signaling modulation, is crucial for understanding the intrinsic mechanisms underlying the host defense, as well as contributing the development of the fight against infectious diseases. Drosophila is an ideal model organism for study of innate immunity. Comparing to mammals, Drosophila immunity is relative conserved and less redundant. A variety of molecular and genetic tools available add further convenience to the research in this system. My work is focused on the signaling modulation by post-translational modification after activation. In these studies I demonstrated in the center of Imd pathway, the Imd protein undergoes proteolytic cleavage, K63-polyubiquitination, phosphorylation, K63-deubiquitination and K48-polyubiquitination/degradation in a stimulation-dependent manner. These modifications of Imd play a crucial role in regulating signaling in response to infection. The characterization of ubiquitin-editing event provides a new insight into the molecular mechanisms underlying the activation and termination of insect immune signaling pathway.

DOI

10.13028/M2GC7X

Rights and Permissions

Copyright is held by the author, with all rights reserved.

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