BRODBELT, JENNIFER S

Jennifer S Brodbelt

Professor
Department of Chemistry

Norman Hackerman Chair in Chemistry


jbrodbelt@cm.utexas.edu

Phone: 512-471-0028

Office Location
WEL 3.424

Postal Address
The University of Texas at Austin
Department of Chemistry, College of Natural Sciences
105 East 24th Street
Stop A5300
Austin, TX 78712

Postdoctoral Studies - University of California at Santa Barbara

Ph.D., Purdue University
B.S., University of Virginia

 

Bioanalytical Mass Spectrometry

The Brodbelt group focuses on the development of ion trap mass spectrometry for a variety of interdisciplinary applications. Research efforts involve a number of aims: A) development of photodissociation methods for characterization of peptides, proteins, and lipids, B) exploration of derivatization methods to enhance the ionization and dissociation of molecules, C) design of new chemical probes to evaluate protein-ligand interactions.

Photodissociation For Analysis Of Biological Molecules

Solving the most challenging biological problems requires advanced analytical strategies for characterizing complex mixtures of biomolecules. We are developing ultraviolet photodissociation methods to unravel the structures of biological molecules. UV photodissociation is a fast, high energy activation method, and it results in rich fragmentation patterns that serve as molecular fingerprints. This methodology is applied to elucidate the sequences and modifications of proteins as well as lipopolysaccharides that decorate the surfaces of bacteria.

Derivatization Methods

Derivatization strategies provide the opportunity to modulate the chemical properties of molecules, ranging from hydrophobicity and basicity to volatility and ionizability. We are developing site-specific derivatization methods to attach charge sites and to append chromophores to molecules to control how peptides ionize and dissociate in the gas phase. UV photodissociation can be used to pinpoint chromophore-tagged molecules in complex mixtures and yield fragmentation patterns amenable to sequencing algorithms.

Chemical Probes

Determination of the correlation between protein structure and function remains a primary objective of biological research, thus motivating the development of advanced analytical tools for unraveling the three dimensional structures of proteins. We are developing an array of site-selective chemical probes that can be used to elucidate protein structure based on the accessibility or exposure of specific protein sites. This methodology is combined with photodissociation to provide detailed conformational maps of proteins.

Representative Publications

Cotham, V.C., Wine, Y., Brodbelt, J.S., “Selective 351 nm Photodissociation of Cysteine-Containing Peptides for Improved Sequencing of Antigen-Binding Regions of IgG Fragments in Bottom-Up LC-MS/MS Workflows” Anal Chem., 2013, 85, 5577-5585.

Shaw, J.B., Li, W., Holden, D.D., Zhang, Y., Griep-Raming, J., Fellers, R.T., Early, B.P., Thomas, P.M., Kelleher, N.L., Brodbelt, J.S., “Complete Protein Characterization Using Top-Down Mass Spectrometry and Ultraviolet Photodissociation”, J. Am. Chem. Soc., 2013, 135, 12646-12651.

 

Madsen, J.A., Xu, H., Robinson, M.R., Horton, A.P., Shaw, J.B., Giles, D.K., , D.Kaoud, T.S., Dalby, K.N, Trent, MS., Brodbelt, J.S., “High-throughput database search and large-scale negative polarity LC-MS/MS with Ultraviolet Photodissociation for Complex Proteomic Samples”, Molecular and Cellular Proteomics, 2013, 12(9), 2604-2614.

Madsen, J.A., Ko, B.Y.., Robotham, S.S., Xu, H., Horton, A.P., Iwashkiw, J.A., Shaw, J.B., Feldman, M.F., Brodbelt, J.S., “Concurrent Automated Sequencing of the Glycan and Peptide Portions of O-Linked Glycopeptide Anions”, Anal. Chem 2013, 85, 9253-9261.

Robotham, S.A., Kluwe, C., Ellington, A., Brodbelt, J.S., “De Novo Sequencing of Peptides Using Selective 351 nm Ultraviolet Photodissociation Mass Spectrometry”, Anal. Chem, 2013, 85, 9832-9838.

O’Brien, J.P., Brodbelt, J.S., “Structural Characterization of Gangliosides and Glycolipids via Ultraviolet Photodissociation Mass Spectrometry”, Anal. Chem., 2013, 85, 10399-10407.

Ellefson, J.W., Meyer, A.J., Hughes, R.A., Cannon, J., Brodbelt, J.S., Ellington, A.D., “Directed evolution of genetic circuits by compartmentalized partnered replication (CPR)”, Nature Biotechnology, 2014, 32(1) 97-101.

Cammarata, M., Lin, K.-Y., Pruet, J., Liu., H.-w., Brodbelt, J.S., “Probing the Unfolding of Myoglobin and Domain C of PARP-1 with Covalent Labeling and Top-Down 193 nm Ultraviolet Photodissociation Mass Spectrometry”, Anal. Chem., 2014, 86, 2534-2542.

O’Brien, J.P., Needham, B.D., Henderson, J.C., Nowicki, E.M., Trent, M.S., Brodbelt, J.S., “193 nm Ultraviolet Photodissociation Mass Spectrometry for the Structural Elucidation of Lipid A Compounds in Complex Mixtures”, Anal. Chem, 2014, 86, 2138-2145.

 

Brodbelt, J.S., “Photodissociation mass spectrometry: New tools for characterization of biological molecules” Chem. Soc. Rev, 2014, 43, 2757-2783.

Cannon, J.R., Cammarata, M.B., Robotham, S.A., Cotham, V.C., Shaw, J.B., Fellers, R.T., Early, B.P., Thomas, P.M., Kelleher, N.L., Brodbelt, J.S., “Ultraviolet photodissociation for characterization of whole proteins on a chromatographic time scale”, Anal. Chem. 2014, 86, 2185-2192.

 

O’Brien, J.P., Needham, B.D., Brown, D.B., Trent, M.S., Brodbelt, J.S., “Top-down strategies for the structural elucidation of intact lipopolysaccharides”, Chemical Science, 2014, 5, 4291-4301.

 

Cannon, J.R., Holden, D.D., Brodbelt, J.S., “Hybridizing Ultraviolet Photodissociation with Electron Transfer Dissociation for Intact Protein Characterization”, Anal. Chem., 2014, 86, 10970-10977.

O’Brien, J.P., Li, W., Zhang, Y., Brodbelt, J.S., “Elucidation of Native Protein Complexes Using Ultraviolet Photodissociation Mass Spectrometry” J. Am. Chem. Soc., 2014, 136, 12920-12928.

Greer, S.M., Cannon, J.R, Brodbelt, J.S., "Improvement of Shotgun Proteomics in the Negative Mode by Carbamylation of Peptides and Ultraviolet Photodissociation Mass Spectrometry", Anal. Chem., 2014, 86, 12285-12290.

Thyer, R., Robotham, S.A., Brodbelt, J.S., Ellington, A., “Evolving tRNASec for efficient canonical incorporation of selenocysteine”, J. Am. Chem. Soc., 2015, 137(1), 46-49.

Cammarata, M., Brodbelt, J.S., “Structural Characterization of Apo-Myoglobin by Ultraviolet Photodissociation”, Chemical Science, 2015, 6, 1324-1333.

Cannon, J.S., Martinez Fonts, K., Robotham, S.A., Matouschek, A., Brodbelt, J.S., “"Top Down 193-nm Ultraviolet Photodissociation Mass Spectrometry For Simultaneous Determination of Polyubiquitin Chain Length and Topology", Anal. Chem., 2015, 87, 1812-1820.

Greer, S.M., Parker, W.R., Brodbelt, J.S., “Impact of protease on ultraviolet photodissociation mass spectrometry for bottom-up proteomics”, J. Proteome Research, 2015, 14(6), 2626-2632.

Cammarata, M.; Thyer, R., Rosenberg, J., Ellington, A., Brodbelt, J.S., “Structural Characterization of Dihydrofolate Reductase Complexes by Top-down Ultraviolet Photodissociation Mass Spectrometry”, J. Am. Chem. Soc., 2015, 137(28) 9128-9135.

Cotham, V., Shaw, J.B., Brodbelt, J.S., “High-Throughput Bioconjugation for Enhanced 193 nm Photodissociation via Droplet Phase Initiated Ion/Ion Chemistry using a Frontend Dual Spray Reactor", Analytical Chemistry, 2015, 87, 9396-9402.