University of Colorado at Boulder

This proposal requests support to develop innovative research strategies in mass spectrometry in order to detect and characterize all proteins in a cellular “proteome” (i.e., all proteins present in a single cell type). Mass spectrometry is the most powerful tool for addressing this problem and worldwide efforts are underway to define the proteomes of organisms, tissues and fluids. However, such efforts are stymied by the inability to comprehensively observe all proteins in highly complex biological samples. The goal is to create innovative experimental and computational technologies that will enhance the accuracy and sensitivity of protein detection by mass spectrometry, and enable comprehensive protein identification. In order to expand the depth to which the proteome can be observed, funds will be used to purchase a high resolution mass spectrometry system with capabilities for electron transfer dissociation. With this instrument, new methods will be developed to overcome limitations in data collection and solve major hurdles in recovering information from large scale datasets. These will be applied to collaborative research efforts between eight laboratories, providing the possibility for unprecedented capabilities to answer questions that were previously impossible to address.