DESORPTION ELECTROSPRAY IONIZATION-MASS SPECTROMETRY IMAGING (DESI-MSI) STUDIES OF CELL METABOLISM ALTERED BY PARASITIC INFECTION AND GENE MUTATION

Abstract

Mass spectrometry (MS) is a powerful tool to study molecules like metabolites, lipids and proteins in biological materials. Regular bulk analysis such as liquid chromatography tandem MS (LC-MS/MS) is a common option to analyze these molecules in a high throughput manner. However, the information provided by LC-MS/MS lacks spatial information. Mass spectrometry imaging (MSI) is a novel technique to study the spatial distribution of biological molecules. MSI data provides m/z value, intensity as well as location information for each molecule and can be reconstructed as ion images to visualize the spatial distribution of each molecule. The heterogeneity of the spatial distribution of metabolites plays a vital role in maintaining the normal functions of different organs in animals. Studying spatial distribution alteration associated with diseases provides us valuable insights into the mechanism of disease pathways, prevention and treatments.This dissertation involves the application of DESI-MSI in metabolites study with animal organ tissue models, including mice heart model with infectious disease Chagas Disease and rat model (cerebellum and skin tissue) with Spinocerebellar Ataxia (SCA) 34. In chapter 1, the principles of different MSI methods are reviewed and compared, and the advantages of using DESI-MSI in this thesis are also discussed. In chapter 2, the infected regions around the parasitic spots in mice heart tissue slices are determined by comparing x-gal-stained T. Cruzi infected mice heart tissue slices and the statistical data analysis of DESI-MSI data. The metabolites changed in gradient within the infected region are also found from the statistical analysis of the DESI-MSI data. In chapter 3, the lipid profile change of rat cerebellum tissue slices with SCA34 mutation are mapped and revealed with DESI-MSI and important lipids altered in cerebellum associated with SCA34 are discussed. In chapter 4, the spatial distribution and alteration of Very Long Chain Fatty Acids (VLCFAs) in different skin layers are revealed in rat skin tissue slices with SCA34 gene mutation with DESI-MSI, and important lipids altered in skin barrier associated with SCA34 are discussed.