All ETDs from UAB

Advisory Committee Chair

Michael Brenner

Advisory Committee Members

Stephen Barnes

Matthew Renfrow

Scott Wilson

Kirill Popov

Document Type

Dissertation

Date of Award

2014

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

The first aim of my thesis was to identify the protein composition of the protein aggregates, called Rosenthal fibers, which are the defining feature of Alexander disease (AxD). AxD is a rare neurodegenerative disease caused by mutations in the astrocyte specific protein, glial fibrillary acidic protein (GFAP). GFAP is a type III intermediate filament protein that is overexpressed in AxD. A guiding hypothesis of this project was that sequestration of vital cell proteins in the aggregates contributed to disease. The results of my research do not support this hypothesis, but do provide an in depth characterization of the protein composition of Rosenthal fibers and is the first study that suggests stress granules may interact with Rosenthal fibers. In the second aim of my thesis I developed a quantitative method for comparative proteomics that is advantageous in several respects to the current state-of-the-art in terms of ease-of-use, quantitative accuracy, and precision. This method uses a computer software program to implement the novel strategy of identifying endogenous, co-eluting peptides as reference standards. This method quantifies approximately 70% more proteins than the current methods, and does so with less technical variability.

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