Ultraviolet Photodissociation Mass Spectrometry

University Of Texas At Austin, Austin TX

Investigators

Abstract

With support from the Chemical Measurement and Imaging program in the Division of Chemistry, Professor Jenny Brodbelt and her group at the University of Texas at Austin are developing innovative methods to characterize proteins using mass spectrometry (MS). Proteins in cells participate in a vast array of functions necessary to sustain life, and the physiological functions and activities of proteins are modulated by structural modifications. Dr. Brodbelt and her group develop new high performance methods that combine MS and both gas-phase separations and reactions to examine proteins and pinpoint the modifications in molecular detail. In particular, the Brodbelt group uses high energy lasers to shatter proteins to create diagnostic fragmentation patterns that reveal structures and modifications. The comprehensive plan engages students at multiple levels in collaborative, interdisciplinary research and provides professional training for the transition to scientific careers. Analysis of intact proteins remains one of the frontiers of proteomics, and the ability to characterize intact proteins offers one of the best means to map combinatorial modifications that play critical roles in protein structure and function. A central hallmark of the Brodbelt group over the past decade is the development and application of ultraviolet photodissociation (UVPD) for analysis of biological molecules. This project emphasizes the development and applications of UVPD for analysis of intact proteins. The main aims integrate dynamic ion manipulation strategies utilizing proton transfer reactions, gas-phase fractionation, and charge detection measurement methods to amplify the information content of MS/MS spectra of intact proteins. UVPD is used to characterize isomers separated by ion mobility via a modular drift cell, and collision cross-sections of proteins are measured. These innovative methods are applied to decipher patterns of post-translational modifications of proteins and extend the mass range of top-down proteomics. The training and mentoring activities forge partnerships with graduate and undergraduate students to encourage their professional development into future leaders in academic and industrial sectors. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.