Author : Zihui Li
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (13 download)
Book Synopsis Advancing Quantitative Proteomics and Protein Post-translational Modification Analyses by Multi-dimensional Mass Spectrometric Approaches by : Zihui Li
Download or read book Advancing Quantitative Proteomics and Protein Post-translational Modification Analyses by Multi-dimensional Mass Spectrometric Approaches written by Zihui Li and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins are important molecules that are involved in numerous critical biological processes. Consequently, understanding the functional roles and dysregulation of proteins constitutes a vital task in both basic and clinical research. However, it is very challenging to define the full complement of proteins due to their large degree of variations, especially considering that many proteins can undergo numerous post-translational modifications (PTMs) which dramatically affect protein conformations and functions. Recently, mass spectrometry (MS) has evolved as a powerful tool to characterize proteins and their PTMs benefiting from its high speed, sensitivity and the ability to monitor thousands of analytes simultaneously. This dissertation is devoted to the development and application of various MS-based strategies to facilitate the detection of proteins and their PTMs qualitatively and quantitatively. A portion of this dissertation describes the investigation of proteome-wide alterations with the development and maturation of human pancreas using custom-developed isobaric tags. This study focuses on the extracellular matrix proteins and provides information on the localization changes of selected proteins in islet or acinar compartments as well. The normal baseline data across the lifespan of human pancreas will become a valuable resource and benefit future studies into the pancreatic pathologies. Switching gear to protein PTMs, this dissertation documents the design and development of a novel biotin thiol tag to greatly improve the in-depth profiling of two important PTMs, citrullination and homocitrullination, from complex biological samples. The utility of the approach is demonstrated by providing the first tissue-specific citrullination and homocitrullination atlas in mice. The first high-throughput quantitative analysis pipeline of protein citrullination is subsequently developed by the integration with isobaric labeling strategy. We also further improve the protein citrullination detection by using a combination of various digestion and fragmentation techniques. Citrullination alteration during the progression of Alzheimer's disease is further explored using human cerebrospinal fluid to shed light on the disease pathogenesis. This dissertation also highlights the application of a novel sub-atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry platform for the in situ imaging of N-glycans. Spatial distribution of N-glycans in ovarian cancer tissue section may indicate potential association of this modification with tumor progression. Collectively, we expect the biological insights and technological advancements presented in this work will lead to improved understanding of microenvironment in both healthy and disease conditions, and the new knowledge gained from these studies will inspire and benefit future research effort in related fields.
