Michael Martynowycz Ph.D.
Michael Martynowycz
Ph.D.
Research Assistant Professor Hs
Department of Structural Biology
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Drug Discovery; Membrane Biophysics; Membrane Proteins; Structural Biology; X-ray Crystallography
Professional Summary:
My research focuses on advancing the field of structural biology through the development and application of novel techniques in electron microscopy and diffraction. My work primarily utilizes Microcrystal Electron Diffraction (MicroED) to determine the structures of biological macromolecules at atomic resolution. By refining sample preparation methods and optimizing data acquisition processes, my research aims to push the boundaries of what is possible in structural determination, particularly for challenging systems such as membrane proteins and small molecules. Additionally, my efforts extend to integrating advanced computational approaches for data analysis, enhancing the ability to visualize dynamic processes within cells. The ultimate goal of my research is to provide deeper insights into the molecular mechanisms of biological systems, thereby informing drug design and therapeutic strategies.
In my career, I have had the privilege of working at leading institutions, including the Howard Hughes Medical Institute and UCLA, where I contributed to groundbreaking research in electron microscopy and diffraction. My work has been recognized with several prestigious awards, including the Sidhu Award from the Pittsburgh Diffraction Society. I have also been actively involved in teaching and mentoring, sharing my expertise in MicroED and structural biology with students and researchers around the world.
Education and Training:
- Fellowship, Postdoctoral Fellowship, David Geffen School of Medicine, University of California (2021)
- Fellowship, Postdoctoral Fellow, Howard Hughes Medical Institute Janelia Research Campus (2018)
- Fellowship, Laboratory-graduate fellowship, Argonne National Laboratory (2016)
- PhD, Physics, Illinois Institute of Technology (2016)
- Fellowship, NSF Education Fellow, Adler Planetarium and Science Museum (2014)
- MS, Physics, Illinois Institute of Technology (2012)
- BS, Mathematics & Theoretical Physics, Loyola University Chicago (2008)
Employment:
- Assistant Investigator, Structural Biology, Hauptman-Woodward Medical Research Institute (2024-present)
- Research Assistant Professor, Biological Chemistry, David Geffen School of Medicine (2023–2024)
- Research Scientist, Structural Biology, Howard Hughes Medical Institute (2021–2023)
Awards and Honors:
- Sidhu Award (2022)
- Breakthrough of the year - runner up (2018)
- Poster Award (2018)
- Dean's Award 2014 (2014)
- Dean's Award 2013 (2013)
- Dean's List (2008)
- Dean's List (2007)
Research Expertise:
- Computational Algorithms for Electron Diffraction Data: We create and implement advanced computational algorithms to process and interpret electron diffraction data. These tools are essential for converting raw diffraction patterns into high-resolution structural models, aiding in the visualization of complex biological systems.
- Cryo-Electron Microscopy (Cryo-EM): Our research leverages cryo-EM to visualize biological macromolecules in their native states. By integrating MicroED with cryo-EM, we extend the capabilities of structural biology to study challenging targets such as membrane proteins, offering insights into their mechanisms at an atomic level.
- Development of MicroED Techniques for Small Molecules: We are pioneering the use of MicroED for the structural determination of small molecules, including pharmaceuticals and novel compounds. This work expands the application of electron diffraction beyond macromolecules, providing valuable structural information for material science and drug discovery.
- Electron Counting and Radiation Damage Mitigation: We develop and refine protocols for electron counting in MicroED, enhancing data quality while mitigating the effects of radiation damage. This allows for more accurate structure determination, even from extremely small or radiation-sensitive crystals.
- Ion Beam Milling for CryoEM and MicroED: We develop advanced methods for thinning macromolecular and small molecular crystals at cryogenic temperatures using gallium and plasma ion beam sources. Our techniques enable the precise preparation of ideal samples for cryoEM and MicroED, facilitating high-resolution structural studies of membrane proteins and viral infection mechanisms in intact, frozen cells. By correlating light, electron, and ion beam images, we optimize sample quality, ensuring accurate and detailed structural analysis.
- Microcrystal Electron Diffraction (MicroED): We utilize MicroED to determine the atomic structures of macromolecules and small molecules from nanocrystals. By advancing techniques in sample preparation, such as focused ion beam (FIB) milling, and optimizing data acquisition methods, we achieve high-resolution structural data that is critical for understanding molecular function.
- Structural Analysis of Membrane Proteins: Our lab specializes in the structural characterization of membrane proteins using MicroED and cryo-EM. Through innovative approaches in sample preparation and data collection, we provide detailed models that reveal the intricate workings of these crucial biological molecules
- Structure-Based Drug Design: By elucidating the atomic structures of biological macromolecules, particularly those involved in disease pathways, we contribute to the rational design of therapeutic agents. Our structural insights inform the development of drugs with improved efficacy and specificity.
Journal Articles:
- Nicolas WJ, Shiriaeva A, Martynowycz MW, Grey AC, Ruma Y, Donaldson PJ, Gonen T. (2024) Structure of the lens MP20 mediated adhesive junction. bioRxiv : the preprint server for biology (May). doi:10.1101/2024.05.13.594022
- Xia X, Sung PY, Martynowycz MW, Gonen T, Roy P, Zhou ZH. (2024) RNA genome packaging and capsid assembly of bluetongue virus visualized in host cells. Cell (Apr), 187(9): 2236-2249.e17. doi:10.1016/j.cell.2024.03.007
- Bardin AA, Haymaker A, Banihashemi F, Lin JYS, Martynowycz MW, Nannenga BL. (2024) Focused ion beam milling and MicroED structure determination of metal-organic framework crystals. Ultramicroscopy (Mar), 257: 113905. doi:10.1016/j.ultramic.2023.113905
- Hattne J, Clabbers MTB, Martynowycz MW, Gonen T. (2023) Electron counting with direct electron detectors in MicroED. Structure (London, England : 1993) (Dec), 31(12): 1504-1509.e1. doi:10.1016/j.str.2023.10.011
- Haymaker A, Bardin AA, Gonen T, Martynowycz MW, Nannenga BL. (2023) Structure determination of a DNA crystal by MicroED. Structure (London, England : 1993) (Dec), 31(12): 1499-1503.e2. doi:10.1016/j.str.2023.07.005
- Martynowycz MW, Andreev K, Mor A, Gidalevitz D. (2023) Cancer-Associated Gangliosides as a Therapeutic Target for Host Defense Peptide Mimics. Langmuir : the ACS journal of surfaces and colloids (Sep), 39(36): 12541-12549.
- Gillman C, Nicolas WJ, Martynowycz MW, Gonen T. (2023) Design and implementation of suspended drop crystallization. IUCrJ (Jul), 10(Pt 4): 430-436. doi:10.1107/S2052252523004141
- Shiriaeva A, Martynowycz MW, Nicolas WJ, Cherezov V, Gonen T. (2023) MicroED structure of the human vasopressin 1B receptor. bioRxiv : the preprint server for biology (Jul). doi:10.1101/2023.07.05.547888
- Hattne J, Clabbers MTB, Martynowycz MW, Gonen T. (2023) Electron-counting in MicroED. bioRxiv : the preprint server for biology (Jun). doi:10.1101/2023.06.29.547123
- Haymaker A, Bardin AA, Gonen T, Martynowycz MW, Nannenga BL. (2023) Structure determination of a DNA crystal by MicroED. bioRxiv : the preprint server for biology (Apr). doi:10.1101/2023.04.25.538338
- Gillman C, Nicolas WJ, Martynowycz MW, Gonen T. (2023) Design and implementation of suspended drop crystallization. bioRxiv : the preprint server for biology (Mar). doi:10.1101/2023.03.28.534639
- Martynowycz MW, Shiriaeva A, Clabbers MTB, Nicolas WJ, Weaver SJ, Hattne J, Gonen T. (2023) A robust approach for MicroED sample preparation of lipidic cubic phase embedded membrane protein crystals. Nature communications (Feb), 14(1): 1086. doi:10.1038/s41467-023-36733-4
- Clabbers MTB, Martynowycz MW, Hattne J, Nannenga BL, Gonen T. (2022) Electron-counting MicroED data with the K2 and K3 direct electron detectors. Journal of structural biology (Dec), 214(4): 107886. doi:10.1016/j.jsb.2022.107886
- Dayeen FR, Brandner BA, Martynowycz MW, Kucuk K, Foody MJ, Bu W, Hall SB, Gidalevitz D. (2022) Effects of cholesterol on the structure and collapse of DPPC monolayers. Biophysical journal (Sep), 121(18): 3533-3541. doi:10.1016/j.bpj.2022.07.007
- Martynowycz MW, Clabbers MTB, Hattne J, Gonen T. (2022) Ab initio phasing macromolecular structures using electron-counted MicroED data. Nature methods (Jun), 19(6): 724-729. doi:10.1038/s41592-022-01485-4
- Martynowycz M, Gonen T. (2022) Unlocking the potential of MICROCRYSTAL ELECTRON DIFFRACTION. Physics today (Jun), 75(6): 38-42. doi:10.1063/pt.3.5019
- Clabbers MTB, Martynowycz MW, Hattne J, Gonen T. (2022) Hydrogens and hydrogen-bond networks in macromolecular MicroED data. Journal of structural biology: X (Jan), 6: 100078. doi:10.1016/j.yjsbx.2022.100078
- Martynowycz MW, Clabbers MTB, Unge J, Hattne J, Gonen T. (2021) Benchmarking the ideal sample thickness in cryo-EM. Proceedings of the National Academy of Sciences of the United States of America (Dec), 118(49). doi:10.1073/pnas.2108884118
- Martynowycz MW, Gonen T. (2021) Protocol for the use of focused ion-beam milling to prepare crystalline lamellae for microcrystal electron diffraction (MicroED). STAR protocols (Sep), 2(3): 100686. doi:10.1016/j.xpro.2021.100686
- Martynowycz MW, Shiriaeva A, Ge X, Hattne J, Nannenga BL, Cherezov V, Gonen T. (2021) MicroED structure of the human adenosine receptor determined from a single nanocrystal in LCP. Proceedings of the National Academy of Sciences of the United States of America (Sep), 118(36). doi:10.1073/pnas.2106041118
- Martynowycz MW, Gonen T. (2021) Microcrystal Electron Diffraction of Small Molecules. Journal of visualized experiments : JoVE (Mar)(169). doi:10.3791/62313
- Halaby S, Martynowycz M, Zhu Z, Tretiak S, Zhugayevych A, Gonen T, Seifrid M. (2021) Microcrystal Electron Diffraction for Molecular Design of Functional Non-Fullerene Acceptor Structures. Chemistry of materials : a publication of the American Chemical Society (Feb), 33(3): 966-977. doi:10.1021/acs.chemmater.0c04111
- Martynowycz MW, Gonen T. (2021) Studying Membrane Protein Structures by MicroED. Methods in molecular biology (Clifton, N.J.) (Jan), 2302: 137-151. doi:10.1007/978-1-0716-1394-8_8
- Martynowycz MW, Gonen T. (2021) Ligand Incorporation into Protein Microcrystals for MicroED by On-Grid Soaking. Structure (London, England : 1993) (Jan), 29(1): 88-95.e2. doi:10.1016/j.str.2020.09.003
- Martynowycz MW, Khan F, Hattne J, Abramson J, Gonen T. (2020) MicroED structure of lipid-embedded mammalian mitochondrial voltage-dependent anion channel. Proceedings of the National Academy of Sciences of the United States of America (Dec), 117(51): 32380-32385. doi:10.1073/pnas.2020010117
- Andreev K, Martynowycz MW, Kuzmenko I, Bu W, Hall SB, Gidalevitz D. (2020) Structural Changes in Films of Pulmonary Surfactant Induced by Surfactant Vesicles. Langmuir : the ACS journal of surfaces and colloids (Nov), 36(45): 13439-13447. doi:10.1021/acs.langmuir.0c01813
- Richards LS, Millán C, Miao J, Martynowycz MW, Sawaya MR, Gonen T, Borges RJ, Usón I, Rodriguez JA. (2020) Fragment-based determination of a proteinase K structure from MicroED data using ARCIMBOLDO_SHREDDER. Acta crystallographica. Section D, Structural biology (Aug), 76(Pt 8): 703-712. doi:10.1107/S2059798320008049
- Martynowycz MW, Hattne J, Gonen T. (2020) Experimental Phasing of MicroED Data Using Radiation Damage. Structure (London, England : 1993) (Apr), 28(4): 458-464.e2. doi:10.1016/j.str.2020.01.008
- Wolff AM, Young ID, Sierra RG, Brewster AS, Martynowycz MW, Nango E, Sugahara M, Nakane T, Ito K, Aquila A, Bhowmick A, Biel JT, Carbajo S, Cohen AE, Cortez S, Gonzalez A, Hino T, Im D, Koralek JD, Kubo M, Lazarou TS, Nomura T, Owada S, Samelson AJ, Tanaka T, Tanaka R, Thompson EM, van den Bedem H, Woldeyes RA, Yumoto F, Zhao W, Tono K, Boutet S, Iwata S, Gonen T, Sauter NK, Fraser JS, Thompson MC. (2020) Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals. IUCrJ (Mar), 7(Pt 2): 306-323. doi:10.1107/S205225252000072X
- Dick M, Sarai NS, Martynowycz MW, Gonen T, Arnold FH. (2019) Tailoring Tryptophan Synthase TrpB for Selective Quaternary Carbon Bond Formation. Journal of the American Chemical Society (Dec), 141(50): 19817-19822. doi:10.1021/jacs.9b09864
- Martynowycz MW, Zhao W, Hattne J, Jensen GJ, Gonen T. (2019) Qualitative Analyses of Polishing and Precoating FIB Milled Crystals for MicroED. Structure (London, England : 1993) (Oct), 27(10): 1594-1600.e2. doi:10.1016/j.str.2019.07.004
- Hattne J, Martynowycz MW, Penczek PA, Gonen T. (2019) MicroED with the Falcon III direct electron detector. IUCrJ (Sep), 6(Pt 5): 921-926. doi:10.1107/S2052252519010583
- Martynowycz MW, Rice A, Andreev K, Nobre TM, Kuzmenko I, Wereszczynski J, Gidalevitz D. (2019) Salmonella Membrane Structural Remodeling Increases Resistance to Antimicrobial Peptide LL-37. ACS infectious diseases (Jul), 5(7): 1214-1222. doi:10.1021/acsinfecdis.9b00066
- de la Cruz MJ, Martynowycz MW, Hattne J, Gonen T. (2019) MicroED data collection with SerialEM. Ultramicroscopy (Jun), 201: 77-80. doi:10.1016/j.ultramic.2019.03.009
- Andreev K, Martynowycz MW, Gidalevitz D. (2019) Peptoid drug discovery and optimization via surface X-ray scattering. Biopolymers (Jun), 110(6): e23274. doi:10.1002/bip.23274
- Martynowycz MW, Zhao W, Hattne J, Jensen GJ, Gonen T. (2019) Collection of Continuous Rotation MicroED Data from Ion Beam-Milled Crystals of Any Size. Structure (London, England : 1993) (Mar), 27(3): 545-548.e2. doi:10.1016/j.str.2018.12.003
- Jones CG, Martynowycz MW, Hattne J, Fulton TJ, Stoltz BM, Rodriguez JA, Nelson HM, Gonen T. (2018) The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination. ACS central science (Nov), 4(11): 1587-1592. doi:10.1021/acscentsci.8b00760
- Sowah-Kuma D, Fransishyn KM, Cayabyab C, Martynowycz MW, Kuzmenko I, Paige MF. (2018) Molecular-Level Structure and Packing in Phase-Separated Arachidic Acid-Perfluorotetradecanoic Acid Monolayer Films. Langmuir : the ACS journal of surfaces and colloids (Sep), 34(36): 10673-10683.
- Andreev K, Martynowycz MW, Huang ML, Kuzmenko I, Bu W, Kirshenbaum K, Gidalevitz D. (2018) Hydrophobic interactions modulate antimicrobial peptoid selectivity towards anionic lipid membranes. Biochimica et biophysica acta. Biomembranes (Jun), 1860(6): 1414-1423. doi:10.1016/j.bbamem.2018.03.021
- Hattne J, Shi D, Glynn C, Zee CT, Gallagher-Jones M, Martynowycz MW, Rodriguez JA, Gonen T. (2018) Analysis of Global and Site-Specific Radiation Damage in Cryo-EM. Structure (London, England : 1993) (May), 26(5): 759-766.e4. doi:10.1016/j.str.2018.03.021
- Martynowycz MW, Gonen T. (2018) From electron crystallography of 2D crystals to MicroED of 3D crystals. Current opinion in colloid & interface science (Mar), 34: 9-16. doi:10.1016/j.cocis.2018.01.010
- Gallagher-Jones M, Glynn C, Boyer DR, Martynowycz MW, Hernandez E, Miao J, Zee CT, Novikova IV, Goldschmidt L, McFarlane HT, Helguera GF, Evans JE, Sawaya MR, Cascio D, Eisenberg DS, Gonen T, Rodriguez JA. (2018) Sub-ångström cryo-EM structure of a prion protofibril reveals a polar clasp. Nature structural & molecular biology (Feb), 25(2): 131-134. doi:10.1038/s41594-017-0018-0
- Vergara S, Lukes DA, Martynowycz MW, Santiago U, Plascencia-Villa G, Weiss SC, de la Cruz MJ, Black DM, Alvarez MM, López-Lozano X, Barnes CO, Lin G, Weissker HC, Whetten RL, Gonen T, Yacaman MJ, Calero G. (2017) MicroED Structure of Au146(p-MBA)57 at Subatomic Resolution Reveals a Twinned FCC Cluster. The journal of physical chemistry letters (Nov), 8(22): 5523-5530. doi:10.1021/acs.jpclett.7b02621
- Andreev K, Martynowycz MW, Ivankin A, Huang ML, Kuzmenko I, Meron M, Lin B, Kirshenbaum K, Gidalevitz D. (2016) Cyclization Improves Membrane Permeation by Antimicrobial Peptoids. Langmuir : the ACS journal of surfaces and colloids (Dec), 32(48): 12905-12913. doi:10.1021/acs.langmuir.6b03477
- Martynowycz MW, Hu B, Kuzmenko I, Bu W, Hock A, Gidalevitz D. (2016) Monomolecular Siloxane Film as a Model of Single Site Catalysts. Journal of the American Chemical Society (Sep), 138(38): 12432-9.
- Feinstein DL, Akpa BS, Ayee MA, Boullerne AI, Braun D, Brodsky SV, Gidalevitz D, Hauck Z, Kalinin S, Kowal K, Kuzmenko I, Lis K, Marangoni N, Martynowycz MW, Rubinstein I, van Breemen R, Ware K, Weinberg G. (2016) The emerging threat of superwarfarins: history, detection, mechanisms, and countermeasures. Annals of the New York Academy of Sciences (Jun), 1374(1): 111-22. doi:10.1111/nyas.13085
- Marangoni MN, Martynowycz MW, Kuzmenko I, Braun D, Polak PE, Weinberg G, Rubinstein I, Gidalevitz D, Feinstein DL. (2016) Membrane Cholesterol Modulates Superwarfarin Toxicity. Biophysical journal (Apr), 110(8): 1777-1788. doi:10.1016/j.bpj.2016.03.004
- Nobre TM, Martynowycz MW, Andreev K, Kuzmenko I, Nikaido H, Gidalevitz D. (2015) Modification of Salmonella Lipopolysaccharides Prevents the Outer Membrane Penetration of Novobiocin. Biophysical journal (Dec), 109(12): 2537-2545. doi:10.1016/j.bpj.2015.10.013