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Mechanisms of Prion Disease: Initial Misfolding of the Prion Protein and Metabolomic Changes in the Brain
DownloadFall 2020
Prion diseases are neurodegenerative diseases that are caused by the misfolding and aggregation of cellular prion protein (PrPC) into the pathogenic form termed PrPSc. To contribute to a better understanding of the mechanism of prion disease, in this thesis I present my work on the structural...
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Fall 2017
The information contained in our genome is essential for the proper functioning of different physiological processes in cells that are required for our growth and survival, making the maintenance of genome integrity a task of utmost priority. Our cells have evolved a highly elaborate, complex and...
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Molecular Mechanisms Underlying the Enhancement of Cardiac Contraction by Modifications of Troponin
DownloadFall 2015
A fine balance between contraction and relaxation is crucial for the heart to function properly. But often the heart cannot contract with enough force to meet the demands of the body. This condition, called systolic heart failure, is the leading cause of death in the modern society. A common...
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An NMR-based approach to the structural and functional investigation of the Na+/H+ exchanger NHE1
DownloadFall 2013
The Na+/H+ exchanger isoform 1 (NHE1) is the predominant isoform in mammalian cells, and regulates intracellular pH and ion concentrations. NHE1 also interacts with numerous proteins and signalling pathways. Consequently, it has been found to influence cell volume, growth, differentiation, and...
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Using 1H-NMR based metabolomics to investigate the pathological consequences of mitochondrial disease and human rabies infection
DownloadSpring 2012
Mitochondrial diseases encompass a wide range of clinical phenotypes. The etiology of these disorders is extremely complex; mitochondria are central to energy metabolism and dysfunction can have a profound effect on global metabolism. The original objective of this thesis was to use 1H-NMR based...
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Structure and dynamics of biomolecules: probing muscle regulation, prion protein unfolding, and drug insertion into DNA by nuclear magnetic resonance spectroscopy
DownloadSpring 2011
Nuclear magnetic resonance (NMR) spectroscopy is a powerful approach to study the structure and dynamics of macromolecules in a close-to-native solution environment. In the present thesis I present my investigation of protein and nucleic acid structure and dynamics in a wide variety of biological...