Discovery-Driven Proteomics to Advance the Evaluation of the Role of Lipids and Lipid Peroxidation-Related Carbonyl Stress in Biological Model Systems

Research has come a long way with the advancement of sequenced genomes in regards to a variety of organisms. In addition, the technology used to explore biological information encoded by these genome sequences has also been enhanced. However, the knowledge of the role that simple components play in biological functions and cellular processes of the organism, from a global perspective, remains limited. With the advent of proteomics, exploring pathways and networks influenced by cellular components such as lipids, has become possible in the context of systems biology. This dissertation has been divided into two parts. Both will focus on a discovery-driven approach to elucidate the diverse biological functions of lipids as well as stress and its consequences in two biological model systems using mass spectrometry-based proteomics. The first part investigates the broader role of phospholipids (specifically phosphatidylglycerol), essential components of biological membranes in prokaryotes and eukaryotes, in a genetically modified strain of cyanobacteria. Ultimately, understanding the impact of lipid-regulation in this simple organism is expected to reveal previously unknown lipid-signaling mechanisms, which could be further investigated in higher-order organisms. The second part is dedicated to the investigation of lipid-signaling mechanisms generated by electrophilic products of oxidative stress-induced lipid peroxidation, and its consequences in disturbing homeostasis in zebrafish embryos. Exploring free radical-mediated lipid peroxidation involved in cellular responses promises a comprehensive understanding of the role and/or contribution that electrophilic products of lipid peroxidation play in modulating oxidative stress-related signaling pathways potentially involved in various pathophysiological dysfunctions. Bioinformatics software successfully constructed networks from the proteins identified as being regulated by the induced carbonyl-stress including intra- and intercellular processes involved in eIF2 signaling, glycolysis, and remodeling of epithelial adherens junctions.