个人简介

Young Investigator Award in Analytical Chemistry, Eli Lilly & Company (2014) Sloan Research Fellowship, Alfred P. Sloan Foundation (2014) Research Award, American Society for Mass Spectrometry (2013) Junior Research Fellowship, Jesus College, University of Oxford Waters Research Fellowship, University of Oxford

研究领域

Bioanalytical and Biophysical Chemistry

Most proteins, particularly those that accomplish complicated tasks, form assemblies with other proteins and molecules that are critical to their function. Established structural biology tools are most effective for highly purified samples that have limited conformational variability, which makes it challenging to apply those methods to capture a systems-wide understanding of the structures, interactions, and dynamics that are present under different cellular conditions. Mass spectrometry is fast, sensitive, tolerant of heterogeneity, and has great potential for assemblies that are extremely challenging to characterize using established tools and for high-throughput structural genomics. Gas-Phase Structural Biology. Gas-phase ions of assemblies can retain significant memories of their native structures in solution. Many measurements of stoichiometry, connectivity, and shape have shown that these aspects of assembly structure can be strongly correlated in both environments. Gas-phase techniques, including mass spectrometry, ion mobility, and ion chemistry will be used to probe the structures of biological assemblies. Accurate models of assemblies, including those that are heterogeneous, dynamic, and/or membrane-bound, will be built based on results from both gas-phase and complementary techniques. Gas-Phase Ion Chemistry. Although many native aspects of biological assembly structure are preserved in the corresponding gas-phase ions, clearly at least some reorganization will occur. Unfortunately, the extents and scales of this reorganization remain poorly understood. A detailed understanding of gas-phase biological assembly ion structure will be developed, with the goal of enabling more accurate and rapid translation of experimental observables into parameters with meaningful uncertainties for building structural models. New gas-phase methods for transforming and fragmenting these ions to gain complementary structural insights will also be developed. Mass Spectrometry of Large Ions. Existing mass spectrometers for gas-phase structural biology yield spectra with decreased sensitivity and increased spectral congestion with increasing assembly size. We intend to develop an instrument for single-ion, gas-phase structural biology that is ideally suited for very large and heterogeneous assemblies that are beyond the reach of current instrumental platforms.

近期论文

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Electron Transfer Reduction of the Diazirine Ring in Gas-Phase Peptide Ions. On the Peculiar Loss of [NH4O] from Photoleucine. Aleš Marek, Christopher J. Shaffer, Robert Pepin, Kristina Slováková, Kenneth J. Laszlo, Matthew F. Bush, František Tureček. J. Am. Soc. Mass. Spectrom. 2015, 26, 415-431. Comprehensive Analysis of Gly-Leu-Gly-Gly-Lys Peptide Dication Structures and Cation-Radical Dissociations Following Electron Transfer: From Electron Attachment to Backbone Cleavage, Ion-Molecule Complexes, and Fragment Separation Robert Pepin, Kenneth J. Laszlo, Bo Peng, Aleš Marek, Matthew F. Bush, František Tureček. J. Phys. Chem. A 2014, 118, 308–324. Effects of Polarity on the Structures and Charge States of Native-like Proteins and Protein Complexes in the Gas Phase Samuel J. Allen, Alicia M. Schwartz, Matthew F. Bush. Anal. Chem. 2013, 85, 12055–12061. Hexamers of the Type II Secretion ATPase GspE from Vibrio cholerae with Increased ATPase Activity Connie Lu, Stewart Turley, Samuel T. Marionni, Young-Jun Park, Kelly K. Lee, Marcella Patrick, Ripal Shah, Maria Sandkvist, Matthew F. Bush, Wim G.J. Hol. Structure 2013, 21, 1707–1717. Gas-Phase Structures of Phosphopeptide Ions: A Difficult Case František Tureček, Christopher L. Moss, Ioannis Pikalov, Robert Pepin, Kerim Gulyuz, Nicolas C. Polfer, Matthew F. Bush, Jeffery Brown, Jonathan Williams, Keith Richardson. Int. J. Mass Spectrom. 2013, 354–355, 249–256 Electron Transfer Dissociation of Photolabeled Peptides. Backbone Cleavages Compete with Diazirine Ring Rearrangements Aleš Marek, Robert Pepin, Bo Peng, Kenneth J. Laszlo, Matthew F. Bush, František Tureček. J. Am. Soc. Mass Spectrom. 2013, 24, 1641–1653. SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket Weiman Xing, Luca Busino, Thomas R. Hinds, Samuel T. Marionni, Nabiha H. Saifee, Matthew F. Bush, Michele Pagano, Ning Zheng. Nature 2013, 496, 64–68. Ion mobility mass spectrometry of peptide ions: effects of drift gas and calibration strategies Matthew F. Bush, Iain D. G. Campuzano, Carol V. Robinson. Anal. Chem. 2012, 84, 7124–7130. Dissecting Heterogeneous Molecular Chaperone Complexes Using a Mass Spectrum Deconvolution Approach Florian Stengel, Andrew J. Baldwin, Matthew F. Bush, Gillian R. Hilton, Hadi Lioe, Eman Basha, Nomalie Jaya, Elizabeth Vierling, Justin L.P. Benesch. Chem. Biol. 2012, 19, 599–607. Traveling-wave ion mobility mass spectrometry of protein complexes: accurate calibrated collision cross-sections of human insulin oligomers Rune Salbo, Matthew F. Bush, Helle Naver, Iain Campuzano, Carol V. Robinson, Ingrid Pettersson, Thomas J. D. Jørgensen, Kim F. Haselmann. Rapid Commun. Mass Spectrom. 2012, 26, 1181–1193. Assigning Structures to Gas-Phase Peptide Cations and Cation-Radicals. An Infrared Multiphoton Dissociation, Ion Mobility, Electron Transfer, and Computational Study of a Histidine Peptide Ion Christopher L. Moss, Julia Chamot-Rooke, Edith Nicol, Jeffery Brown, Iain Campuzano, Keith Richardson, Jonathan P. Williams, Matthew F. Bush, Benjamin Bythell, Bela Paizs, Frantisek Turecek. J. Phys. Chem B 2012, 116, 3445–3456. Charge-State Dependent Compaction and Dissociation of Protein Complexes – Insights from Ion Mobility and Molecular Dynamics Zoe Hall, Argyris Politis, Matthew F. Bush, Lorna J. Smith, and Carol V. Robinson. J. Am. Chem. Soc. 2012, 134, 3429–3438. Structural Characterization of Drug-like Compounds by Ion Mobility Mass Spectrometry: Comparison of Theoretical and Experimentally Derived Nitrogen Collision Cross-sections Iain Campuzano, Matthew F. Bush, Carol V. Robinson, Claire Beaumont, Keith Richardson, Hyungjun Kim, Hugh I. Kim. Anal. Chem. 2012, 84, 1026-1033. Gas-Phase Protein Assemblies: Unfolding Landscapes and Preserving Native-Like Structures Using Noncovalent Adducts Joanna Freeke, Matthew F. Bush, Carol V. Robinson, Brandon T. Ruotolo. Chem. Phys. Lett. 2012, 524, 1-9. (Link) Collision Cross Sections of Proteins and their Complexes: a Calibration Framework and Database for Gas-Phase Structural Biology Matthew F. Bush, Zoe Hall, Kevin Giles, John Hoyes, Carol V. Robinson, Brandon T. Ruotolo. Anal. Chem. 2010, 82, 9557-9565. Defining the mechanism of polymerization in the serpinopathies Ugo I. Ekeowa, Joanna Freeke, Elena Miranda, Bibek Gooptu, Matthew F. Bush, Juan Pérez, Jeff Teckman, Carol V. Robinson, David A. Lomas. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 17146–17151. Sulfate Ion Patterns Water at Long Distances Jeremy T. O’Brien, James S. Prell, Matthew F. Bush, Evan R. Williams. J. Am. Chem. Soc. 2010, 132, 8248–8249. Hydration of Alkaline Earth Metal Dications: Effects of Metal Ion Size Determined Using Infrared Action Spectroscopy Matthew F. Bush, Jeremy T. O’Brien, James S. Prell, Chih-Che Wu, Richard J. Saykally, Evan R. Williams. J. Am. Chem. Soc. 2009, 131, 13270–13277. Proton Affinity and Zwitterion Stability: New Results from Infrared Spectroscopy and Theory of Cationized Lysine and Analogues in the Gas Phase Matthew F. Bush, Jos Oomens, Evan R. Williams. J. Phys. Chem. A 2008, 113, 431–438. Infrared Action Spectra of Ca2+(H2O)11–69 Exhibit Spectral Signatures for Condensed-Phase Structures with Increasing Cluster Size Matthew F. Bush, Richard J. Saykally, Evan R. Williams. J. Am. Chem. Soc. 2008, 130, 15482–15489. Alkali Metal Ion Binding to Glutamine and Glutamine Derivatives Investigated by Infrared Action Spectroscopy and Theory Matthew F. Bush, Jos Oomens, Richard J. Saykally, Evan R. Williams. J. Phys. Chem. A 2008,112, 8578–8584. Reactivity and Infrared Spectroscopy of Gaseous Hydrated Trivalent Metal Ions Matthew F. Bush, Richard J. Saykally, Evan R. Williams.J. Am. Chem. Soc. 2008, 130, 9122–9128.