Dr. Alan G. MarshallRobert O. Lawton Distinguished Professor
Ph.D. (1970) Stanford University Chief Scientist, Ion Cyclotron Resonance Program, NHMFL
Research InterestFOURIER TRANSFORM ION CYCLOTRON RESONANCE (FT-ICR) MASS SPECTROMETRY
My research consists of the continuing development of new theory, techniques, and analytical/biological/environmental applications of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. We were the first to apply Fourier transform techniques to mass spectrometry, and more than 800 FT-ICR mass spectrometry systems based on our patents and papers have been bought or built worldwide. At our National NSF High-Field FT-ICR Mass Spectrometry Facility at the National High Magnetic Field Laboratory, we currently offer 9.4, 9.4, 14.5, and 21 tesla (highest magnetic field in the world for FT/ICR) instruments. Our instruments hold world records for broadband mass resolution and mass accuracy (e.g., see Figure), and attract hundreds of users and collaborators from all over the world.
We continue to push the FT-ICR technique to its ultimate limits for mass resolution, mass range, and sensitivity. Our stored-waveform inverse Fourier transform ("SWIFT") excitation/detection scheme offers ultrahigh-resolution MS/MS with a single spectrometer as well as truly simultaneous multiple-ion monitoring. We use atmospheric pressure ionization (electrospray, photoionization, chemical ionization, and thermal and laser desorption ionization) to produce mass spectra for substances with little or no volatility (e.g., biopolymers, drugs). We employ robotic sample handling for generation and introduction of biologically interesting ions (e.g., lipids, peptides/proteins, metabolites) into an ICR ion trap for ultrahigh-resolution MS or MS/MS analysis. We optimize MS/MS (electron capture/transfer dissociation, collision-activated dissociation, infrared multiphoton dissociation) methods to identify the primary amino acid sequence as well as the site(s) and nature (e.g., phosphorylation, glycosylation) of protein posttranslational modifications. Applications include discovery and characterization of disease biomarkers.
FT-ICR MS allows us to identify 100,000 components in a mixture without prior separation (GC, LC , gels), thereby changing the whole approach to mixture analysis. For each component, the elemental composition reveals the heteroatom content (numbers of N, S, O atoms), number of rings plus double bonds, and degree of alkylation, from which we correlate and ultimately predict the origin, properties, and behavior of petroleum crude oil and its distillates, as well as other complex mixtures (e.g., biofuels). We are developing new numerical and graphical methods to recognize patterns in the enormous volume of data made available by FT-ICR MS (up to 8 Mwords per spectrum).
Finally, we monitor H/D exchange by mass spectrometry to identify surface-exposed residues in proteins and protein complexes. When two proteins stick to each other, we can identify amino acid residues at the contact surface between the two proteins, as prospective drug targets. Applications range from drug screening to epitope mapping of antigen:antibody complexes.
|Hendrickson, Christopher L.; Quinn, John P.; Kaiser, Nathan K.; Smith, Donald F.; Blakney, Greg T..; Chen, Tong; Marshall, Alan G.; Weisbrod, Chad R.; Beu, Steven C. 21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: A National Resource for Ultrahigh Resolution Mass Analysis. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2015, Volume 26, 1626-1632.|
|Brownstein, Naomi C.; Guan, Xiaoyan; Mao, Yuan; Zhang, Qian; DiMaggio, Peter A.; Xia, Qiangwei; Zhang, Lichao; Marshall, Alan G.; Young, Nicholas L. "Paired Single Residue-Transposed Lys-N and Lys-C Digestions for Label-Free Identification of N-Terminal and C-Terminal MS/MS Peptide Product Ions: Ultrahigh Resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry for Peptide De Novo Sequencing. RAPID COMMUNICATIONS IN MASS SPECTROMETRY 2015, Volume 29, 659-666.|
|Ruddy, Brian M.; Huettel, Markus; Kostka, Joel E.; Lobodin, Vladislav V.; Bythell, Benjamin J.; McKenna, Amy M.; Aeppli, Christoph; Reddy, Christopher M.; Nelson, Robert K.; Marshall, Alan G.; Rodgers, Ryan P. Targeted Petroleomics: Analytical Investigation of Oxidation Products of Macondo Well Oil from Pensacola Beach. ENERGY & FUELS 2014, Volume 28, 4043-4050.|
|Scotcher, Jenna; Bythell, Benjamin J.; Marshall, Alan G. Unequivocal Determination of Site-Specific Protein Disulfide Bond Reduction Potentials by Top-down FT-ICR MS: Characterization of the N- and C-Terminal Redox-Active Sites in Human Thioredoxin 1. ANALYTICAL CHEMISTRY 2013, Volume 85, 9164-9172.|
|Noble, Alex J.; Zhang, Qian; O'Donnell, Jason; Hariri, Hanna; Bhattacharya, Nilakshi; Marshall, Alan G.; Stagg, Scott M. A Pseudoatomic Model of the COPII Cage Obtained from Cryo-Electron Microscopy and Mass Spectrometry. NATURE STRUCTURAL & MOLECULAR BIOLOGY 2013, Volume 20, 167-174.|