Ultraviolet Photodissociation and Ion Mobility Mass Spectrometry for Top-Down Characterization of Nucleic Acids

With support from the Chemical Measurement and Imaging program in the Division of Chemistry, Professor Jennifer S. Brodbelt of the University of Texas at Austin will develop innovative methods to characterize nucleic acids using mass spectrometry. Nucleic acids are being developed for many purposes, including therapeutics, sensors, diagnostics, and data storage. Dr. Brodbelt and her group will design and implement novel analytical methods that integrate high performance mass spectrometry and gas-phase separations to determine the structures of nucleic acids and elucidate their interactions with other molecules. Laser-based photoactivation will be used to dissociate nucleic acid ions to pinpoint modifications with high sensitivity. Students at multiple levels will participate in collaborative, interdisciplinary research and engage in professional development to support their future careers. Training students as innovative scientific leaders is a key driver for this research program. The enormous degree of programmability of nucleic acids, meaning the ability to modulate shapes, sizes, and properties in order to modify functions, affords many opportunities for development of new functional materials. The broad range of structures and properties of nucleic acids results in many analytical challenges that must be solved in order to determine the sequences, modifications, structures, conformational shapes, and functional motifs, and therefore understand structure/functional relationships that are critical for harnessing nucleic acid materials. These challenges motivate the Brodbelt research group to advance new mass spectrometry strategies to decipher the structural features of nucleic acids. This research effort focuses on the development photodissociation and ion mobility methods to provide extensive structural insight into nucleic acids and their assembly with other molecules. Charge reduction methods and charge detection measurements will increase the sensitivity and resolution of the mass spectrometry analysis. Numerous collaborations with both academic and industrial partners will expand and disseminate both innovative analytical methods and software while also increasing interdisciplinary familiarity with advanced mass spectrometry methods for solving biological problems. 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.