# Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules

> **NIH NIH R35** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $100,420

## Abstract

Abstract. Understanding the functions of lipids, proteins and even larger macromolecular assemblies
depends on deciphering complex structures of individual molecules as well as decrypting how those
molecules interact, often via networks of non-covalent interactions. In order to advance the elucidation of
biomolecular organization and functional outcomes, new methods are needed to push the limits of
structural insight, providing more detailed holistic chemical information with greater sensitivity. The critical
interplay between structure/function is evidenced in numerous biologically-motivated problems, ranging
from understanding the ways that pathogenic bacteria develop antibiotic resistance to the design of new
drugs that selectively bind and inhibit the functions of protein targets. The ongoing need for even greater
chemical insight has motivated my group’s effort to develop innovative mass spectrometry methods to
characterize structures of biological molecules in unprecedented detail, especially lipids and proteins
which are featured in this proposal. The overarching goal of my research program is to develop state-of-
the-art tandem mass spectrometry technologies, particularly highlighting ultraviolet photodissociation
(UVPD) and hybrid MS/MS methods, for structural elucidation of lipids, proteins, and protein complexes.
These new methods will be showcased for solving challenging problems in three areas. (1) Lipids: (i)
profiling lipids of pathogenic bacteria and their signatures of antibiotic resistance, and (ii) structural
characterization of unsaturations, oxidations and modifications of lipids that occur during remodeling of
cellular membranes. (2) Protein complexes: (i) characterization of protein-ligand complexes, membrane
protein complexes, protein/nucleic acid complexes, and macromolecular assemblies, and (ii) advancing
capillary electrophoresis for native separations and exploration of the interactome. (3) Post-translational
modifications: focusing on decoding the phosphorylation patterns of the C-terminal domain of RNA
polymerase II which regulates transcription. These high impact problems are supported via numerous
collaborations with microbiology and molecular biology groups who recognize the value of frontier mass
spectrometry strategies for elevating biomedical research. This supplement supports acquisition of an
ExD cell to enable electron-based activation on existing mass spectrometers and a solvent evaporator to
accelerate sample preparation workflows. The ExD cell will support research areas 2 and 3 by allowing
electron capture dissociation and charge reduction capabilities for analysis of post-translational
modifications and cleavage of disulfide bonds in proteins. The solvent evaporator will facilitate
preparation of samples in all three research areas.

## Key facts

- **NIH application ID:** 10389836
- **Project number:** 3R35GM139658-01S1
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Jennifer S. Brodbelt
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $100,420
- **Award type:** 3
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389836

## Citation

> US National Institutes of Health, RePORTER application 10389836, Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules (3R35GM139658-01S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10389836. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*