Degrees and Appointments
- B.A. 2010, St. Olaf College
- Ph.D. 2013, University of Illinois at Urbana-Champaign
- Postdoctoral Researcher 2013-2016, University of Oxford
- Assistant Professor 2016, University of Arizona
Awards and Honors
- American Society for Mass Spectrometry Research Award, 2018
- Bisgrove Scholar Award, 2017
- Robert C. and Carolyn J. Springborn Fellow, 2010-2013
- Phi Beta Kappa, 2009
Membrane proteins play a number of critical biochemical roles and make up the majority of drug targets. Despite their importance, membrane proteins remain challenging systems for analysis due to their amphipathic nature and low expression levels. Moreover, the lipid bilayer can play an important but largely unexplored role in regulating membrane protein structure and function. New analytical and biochemical methods are necessary to better understand and design drugs to target membrane proteins.
Membrane protein AmtB modeled in a POPC membrane (top) and a Nanodisc (bottom)
Research in the Marty lab is focused on developing mass spectrometry methods to study the structure and biophysics of membrane proteins. Working at the interface of Analytical Chemistry and Biochemistry, we utilize lipoprotein Nanodiscs to solubilize membrane proteins in a lipid bilayer with a defined composition. Nanodiscs are nanoscale discoidal lipid bilayers encircled by two amphipathic membrane scaffold proteins.
By using nondenaturing nano-electrospray ionization, we can keep the Nanodisc complex intact inside the mass spectrometer and gradually release the membrane protein with collisional activation. This approach, known as noncovalent or native mass spectrometry, allows us to measure the stoichiometry and lipid composition in large protein-lipid complexes to better understand protein-lipid interactions in membrane protein receptors and transporters. We are also using these approaches to study interactions of antimicrobial peptides with and within lipid bilayers.
Following electrospray ionization, Nanodiscs are activated by gas-phase collision induced dissociation (CID) to release the membrane protein bound to dozens of lipids for high-resolution Orbitrap mass analysis, which results in a highly complex spectral pattern.
Because mass spectra of Nanodiscs are highly complex, we are interested in development of new computational approaches and software for analysis of native MS data. This work builds on UniDec, software we have developed to rapidly and robustly deconvolve mass and ion mobility spectra. We are also interested in developing cross-linking and covalent labeling approaches to use bottom-up proteomics to study the structure of membrane proteins in their native membrane environment.
Walker, L. R.; Marzluff, E. M.; Townsend, J. A.; Resager, W. C.; Marty, M. T. “Native Mass Spectrometry of Antimicrobial Peptides in Lipid Nanodiscs Elucidates Complex Assembly.” Anal. Chem. 2019, 91, 9284-9291.
Kostelic, M.M.; Ryan, A.M.; Reid, D.J.; Noun, J.M.; Marty, M.T. “Expanding the Types of Lipids Amenable to Native Mass Spectrometry of Lipoprotein Complexes.” J. Am. Soc. Mass Spectrom. 2019, 30, 1416-1425.
Keener, J.E.; Zambrano, D.E.; Zhang, G.; Zak, C.K.; Reid, D.J.; Deodhar, B.S.; Pemberton, J.E.; Prell, J.S.; Marty, M.T. “Chemical additives enable native mass spectrometry measurement of membrane protein oligomeric state within intact nanodiscs.” J. Am. Chem. Soc. 2019, 141, 1054-1061.
Reid, D.J.; Diesing, J.D.; Miller, M.A.; Perry, S.M.; Wales, J.A.; Montfort, W.R.; Marty, M.T. “MetaUniDec: High-throughput Deconvolution of Native Mass Spectra” J. Am. Soc. Mass Spectrom. 2019, 30, 118-127.
Reid, D.J.; Keener, J.E.; Wheeler, A.P.; Zambrano, D.E.; Diesing, J.M.; Reinhardt-Szyba, M.; Makarov, A.A.; Marty, M.T. “Engineering Nanodisc Scaffold Proteins for Native Mass Spectrometry” Anal. Chem. 2017, 89, 11189-11192.
Marty, M.T.; Hoi, K.K.; Robinson, C.V. “Interfacing Membrane Mimetics with Mass Spectrometry” Acc. Chem. Res. 2016, 49, 2459–2467.NanodiscsMembrane ProteinsNative Mass SpectrometryDeconvolution