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Andrew H. Marcus

  • Title: Professor
  • Additional Title: Physical Chemistry, Department Head
  • Phone: (541) 346-4809
  • Office: 175A Klamath Hall
  • Affiliated Departments: Institute of Molecular Biology, Materials Science Institute, Oregon Center for Optics

Education

B.A., University of California, San Diego, 1987. Ph.D., Stanford University, 1994 (Michael D. Fayer). Postdoctoral: University of Chicago, James Franck Institute, 1994-96 (Stuart A. Rice). Honors and Awards: American Chemical Society Western States Regional Scholar, 1987; American Institute of Chemists Student Research Recognition Foundation Scholar, 1987; Harold Urey Award for Outstanding Excellence in Chemistry, 1987; University of California, San Diego Outstanding Freshman in Chemistry; Provost's Honor List, 1982-1987; Research Corporation Innovation Award, 1997; NSF CAREER Award, 1998. At Oregon since 1996.

Research

The Marcus group studies the structure and dynamics of macromolecules in biological environments. These include the diffusive motions and internal structural changes of proteins in membranes and in living cells, as well as the conformational fluctuations of macromolecular machines that interact with and manipulate DNA.

To elucidate the conformations of macromolecular complexes, and to monitor their time dependent behavior, we develop and apply linear and nonlinear spectroscopic methods that are sensitive to the electronic couplings between fluorescent chromophore labels. Spectroscopic characterization of exciton-coupled dimer probes, which are attached at specific locations on the macromolecules, allows us to observe functionally important macromolecular conformations. For example, by using fluorescent nucleic acid analogues placed at sites near the forks and junctions of primer-template DNA, we study the effects of protein-DNA interactions on local base-stacking conformation. In collaboration with UofO Prof. Peter von Hippel, we are investigating the mechanisms of polymerase and helicase, two protein-DNA complexes central to gene expression. Extension of our techniques to single molecule fluorescence imaging allows us to observe bio-molecular events in real time.

Molecular studies of how protein machines enact and regulate gene expression are critical to understand the chemical basis of life processes.

We developed phase-modulation two-dimensional fluorescence spectroscopy (PM-2D FS) to characterize the exciton-coupling of dimer probes, and to determine dimer conformation. These experiments yield two-dimensional optical spectra, which in analogy to two-dimensional nuclear magnetic resonance (2D NMR), provide information about the couplings between molecular electronic states.

The PM-2D FS instrument (above) produces sequences of tunable ultrafast optical pulses (schematically represented below).

The conformation of molecular complexes are determined by comparing the results of computer simulated models to experimental PM-2D FS data.

University of Oregon graduate student Eric Senning (left) and undergraduate Jimmy Utterback (right) prepare single-molecule fluorescence instrumentation.

Marcus and von Hippel combined group photo. From left to right. Back row: John Gillies, Huiying Ji, Carey Phelps, Julia Widom, Susan Scott, Pete von Hippel, Brett Isreals, Steve Weitzel, Tom Steinberg, Davis Jose, Neil Johnson, Andy Marcus. Front row: Loni Kringle, Rocky (the dog), Mari Saif, Wonbae Lee.

Publications

Lee, W.; von Hippel, P. H.; Marcus, A. H. “Internally labeled Cy3 / Cy5 DNA constructs show greatly enhanced photostability in single-molecule FRET experiments,” Nucleic Acids Research, 2014, 42, 5967 – 5977. doi: 10.1093/nar/gku199

Raymer, M. R.; Marcus, A. H.; Widom, J. R.; Vitullo, D. L. P. “Entangled photon-pair two dimensional fluorescence spectroscopy (EPP-2DFS),” Prof. Michael D. Fayer Festschrift special issue, guest editors: A. H. Marcus, M. A. Berg, and J. Zheng, Journal of Physical Chemistry B, 2013, 117, 15559-15575. Doi/10.1021/jp405829n.
 
Phelps, C.; Lee, W.; Jose, D.; von Hippel, P. H.; Marcus, A. H. “Single-Molecule FRET and Linear Dichroism Studies of DNA ‘Breathing’ and Helicase Binding at Replication Fork Junctions,” Proc. Nat. Acad. Sci.2013110, 17320 – 17325. doi/10.1073/ pnas.1314862110. See also editorial commentary: Fei, J.; Ha, T. “Watching DNA breathe one molecule at a time,” Proc. Nat. Acad. Sci.2013110, 17173 – 17174. doi:10.1073/pnas.1314862110.
 
von Hippel, P. H.; Johnson, N. P.; Marcus, A. H. “50 Years of DNA ‘Breathing’: Reflections on Old and New Approaches,” special issue of Biopolymers: 50th anniversary of Nucleic Acids Research, Biopolymers, 2013, 99, 923 – 954. Doi:10.1002/bip.22347

Widom, J. R.; Perdomo-Ortiz, A.; Lee, W.; Rappoport, D.; Molinski, T. F.; Aspuru-Guzik, A.; Marcus, A. H. "Temperature-Dependent Conformations of a membrane supported 'zinc porphyrin tweezer' by 2D Fluorescence Spectroscopy," Invited research article for special issue Prof. John C. Wright Festschrift. J. Phys. Chem. A. 2013, 117, 6171 – 6184. Doi: http://dx.doi.org/10.1021/jp400394zv

Widom, J. R.; Johnson, N. P.; von Hippel, P. H.; Marcus, A. H. "Solution Conformation of 2-Aminopurine (2-AP) Dinucleotide by Ultraviolet 2D Fluorescence Spectroscopy (UV-2D FS)," Invited research article for special issue on 2D optical coherence spectroscopy, New J. Phys., 2013, 15, 025028-1-16. http://dx.doi.org/10.1021/jp400394z

Lee, W.; Jose, D.; Phelps, C.; Marcus, A. H; von Hippel, P. H. "A Single-Molecule View of the Assembly Pathway, Subunit Stoichiometry and Unwinding Activity of the Bacteriophage T4 Primosome (Helicase-Primase) Complex," Biochemistry, 2013, 52, 3157 – 3170. http://dx.doi.org/10.1021/bi400231s

Karki, K. J.; Torbjornsson, M.; Widom, J. R.; Marcus, A. H.; Pullerits, T. "Digital Cavities and their Potential Applications," Journal of Instrumentation, 2013, 8, T05005-1-12. Doi: http://iopscience.iop.org/1748-0221/8/05/T05005

Widom, J. R.; Rappoport, D.; Perdomo-Ortiz, A.; Thomsen, H.; Johnson, N. P.; von Hippel, P. H.; Aspuru-Guzik, A.; Marcus, A. H. “Electronic Transition Moments of 6-Methyl isoxanthoptherin (6-MI) – A Fluorescent Analog of Guanine,” Nucleic Acids Research, 2013, 41, 995 – 1004. Doi:10.1093/nar/gks1148

Sanders, J. N.; Mostame, S.; Saikin, S. K.; Andrade, X.; Widom, J. R.; Marcus, A. H.; Aspuru-Guzik, A. “Compressed Sensing for Multidimensional Spectroscopy Experiments,” J. Phys. Chem. Lett. 2012, 3, 2697-2702.

Perdomo, A.; Widom, J. R.; Lott, G. A.; Aspuru-Guzik, A.; Marcus, A. H. “Conformation and Electronic Population Transfer in Membrane Supported Self-Assembled Porphyrin Dimers by Two-Dimensional Fluorescence Spectroscopy,” J. Phys. Chem. B 2012, 116, 10757-10770.

Datta, K.; Johnson, N. P.; Villani, G.; Marcus, A. H.; von Hippel, P. H. "Characterization of the 6-Methyl Isoxanthoptherin (6-MI) Base Analogue Dimer, A Spectroscopic Probe for Monitoring Guanine Base Conformation at Specific Sites in Nucleic Acids," Nucl. Acids Res., 2012, 40, 1191-1202.

Lott, G. A.; Perdomo-Ortiz, A.; Utterback, J. K.; Widom, J. R.; Aspuru-Guzik, A.; Marcus, A. H. "Conformation of Self-Assembled Porphyrin Dimers in Liposome Vesicles by Phase-Modulation 2D Fluorescence Spectroscopy," Proc. Nat. Acad. Sci., 2011, 108, 16521-16526.

Senning, E. N.; Marcus, A. H. “Subcellular Dynamics and Protein Conformation Fluctuations Measured by Fourier Imaging Correlation Spectroscopy,” (invited review for Ann. Rev. Phys. Chem., 2010, 61, 111-28.

Senning, E. N.; Marcus, A. H. “Actin Polymerization Driven Mitochondrial Transport in Mating S. cerevisiae,” Proc. Nat. Acad. Sci., 2010. 107, 721-725.

Tekavec, P. F.; Lott, G. A.; Marcus, A. H. “Fluorescence-Detected Two-Dimensional Electronic Coherence Spectroscopy by Acousto-Optic Phase Modulation,” Proceedings of the 16th International Conference (2009), 1060 XVI International Conference on Ultrafast Phenomena, Stresa, Italy (06/09/2008-06/13/2008) Springer, Heidelberg.

Senning, E. N.; Lott, G. A.; Fink, M. C.; Marcus, A. H. “II. Kinetic pathways of switching optical conformations in DsRed by 2D Fourier imaging correlation spectroscopy.” J. Phys. Chem. B 2009, 113, 6854-6860.

Lott, G. A.; Senning, E. N. ; Fink, M. C.; Marcus, A. H. “I. Conformational dynamics of biological macromolecules by polarization-modulated Fourier imaging correlation spectroscopy.” J. Phys. Chem. B 2009, 113, 6847-6853.

Senning, E. N.; Lott, G. A.; Marcus, A. H. “Fourier imaging correlation spectroscopy for studies of intracellular structure-function,” (invited chapter) Meths. Cell Biol. 2008, 90, 117-137.

Fink, M. C.; Marcus A. H. “Simultaneous Measurement of Molecular Anisotropy and Translation by Polarization Modulated MFICS” Philosophical Magazine 2008, 88, 3947-3951.

Tekavec, P. F.; Lott, G. A.; Marcus, A. H. “Fluorescence-Detected Two-Dimensional Electronic Coherence Spectroscopy by Acousto-Optic Phase Modulation,” J. Chem. Phys. 2007, 127, 214307-1-21. Selected for publication in the January 2007 issue of the Virtual Journal of Ultrafast Science (see: www.vjultrafast.org).

Goulding, M. B.; Canman, J. C.; Senning, E. N.; Marcus, A. H.; Bowerman, B. “Control of Nuclear Centration in the C. elegans Zygote by Receptor-Independent G Signaling and Myosin II,” J. Cell Biol. 2007, 178, 1177-1191.

Tekavec, P. F.; Dyke, T. R.; Marcus, A. H. “Wave Packet Interferometry and Quantum State Reconstruction by Acousto-Optic Phase Modulation,” J. Chem. Phys. 2006, 125, 194303-1-19. Selected for publication in the December 2006 issue of the Virtual Journal of Ultrafast Science (see: www.vjultrafast.org).

Fink, M. C.; Adair, K. V.; Guenza, M. G.; Marcus, A. H. “Translational Diffusion of Fluorescent Proteins by Molecular Fourier Imaging Correlation Spectroscopy,” Biophys. J. 2006, Volume 91, 3482-3498.

Knowles, M. K.; Honerkamp-Smith, A. R.; Marcus, A. H. “Direct Measurement of the Relative and Collective Diffusion in a Dilute Binary Suspension of Colloidal Particles,” J. Chem. Phys. 2005, 122, 234909-1-13.

Knowles, M. K., M. G. Guenza, R. A. Capaldi, and A. H. Marcus, "Cytoskeletal-assisted dynamics of the mitochondrial reticulum in living cells." Proc. Nat. Acad. Sci. 2002, 99, 14772-14777.

Additional Publications

1. Zabriskie, T. M.; Klocke, K. A.; Ireland, C. M.; Marcus, A. H.; Molinski, T. F.; Faulkner, D. J.; Xu, C.; Clardy, J. “Jaspamide, a Modified Peptide from a Jaspis Sponge, with Insecticidal and Anti-fungal Activity,” J. Am. Chem. Soc. 1986, 108, 3123 – 3126.

2. Marcus, A. H.; Molinski, T. F.; Fahy, E.; Faulkner, D. J.; Xu, C.; Clardy, J. “5-Isothiocyanatopupukeanane from a Sponge of the Genus Axinyssa,” J. Org. Chem. 1989, 54, 5184 – 5188.

3. Marcus, A. H.; Fayer, M. D. “Electronic Excitation Transfer in Clustered Chromophore Systems: Calculations of Time-Resolved Observables for Intercluster Transfer,” J. Chem. Phys. 1991, 94, 5622 – 5630.

4. Stein, A. D.; Hoffmann, D. A.; Marcus, A. H.; Leezenberg, P. B.; Frank, C. W.; Fayer, M. D. “Dynamics in Poly(dimethylsiloxane) Melts: Fluorescence Depolarization Measurements of Probe Chromophore Orientational Relaxation, ” J. Phys. Chem. 1992, 96, 5255 – 5263.

5. Marcus, A. H.; Diachun, N. A.; Fayer, M. D. “Electronic Excitation Transfer in Concentrated Micelle Solutions,” J. Phys. Chem. 1992, 96, 8930 – 8937.

6. Quitevis, E. L.; Marcus, A. H.; Fayer, M. D. “Dynamics of Ionic Lipophilic Probes in Micelles: Picosecond Fluorescence Depolarization Measurements,” J. Phys. Chem. 1993, 97, 5762 – 5769.

7. Marcus, A. H.; Diachun, N. A.; Fayer, M. D. “Intermolecular Structure in a Polymer Glass: Electronic Excitation Transfer Studies,” Macromolecules 1993, 26, 3041 – 3048.

8. Finger, K. U.; Marcus, A. H.; Fayer, M. D. “Structure of Complex Systems using Electronic Excitation Transport: Theory, Monte Carlo Simulations, and Experiments on Micelle Solutions,” J. Chem. Phys. 1994, 100, 271 – 286.

9. Diachun, N. A.; Marcus, A. H.; Fayer, M. D. “Dynamics in Polydimethylsiloxane: The Effect of Solute Polarity,” J. Am. Chem. Soc. 1994, 116, 1027 – 1032.

10. Marcus, A. H.; Fayer, M. D.; Curro, J. G. “Intermolecular Structure in a Single Component Polymer Glass: Towards High Resolution Measurements of the Side Chain Pair Correlation Function,” J. Chem. Phys. 1994, 100, 9156 – 9169.

11. Marcus, A. H.; Hussey, D. M.; Diachun, N. A.; Fayer, M. D. “Nanodomain Formation in a Liquid Polymer Blend: the Initial Stages of Phase Separation,” J. Chem. Phys. 1995, 103, 8189 – 8201.

12. Leezenberg, P. B.; Marcus, A. H.; Fayer, M. D.; Frank, C. W. “Rotational Dynamics of Naphthalene-Labeled Cross-link Junctions in Poly(dimethylsiloxane) Elastomers,” J. Phys. Chem. 1996, 100, 7646 – 7655.

13. Marcus, A. H.; Morkved, T.; Jaeger, H.; Rice, S. A.; Hussey, D.; Diachun, N. A.; Fayer, M. D. “Chromophore-Rich Nanodomains in Bulk and Ultra-Thin Film Polymer Blends,” Mol. Cryst. Liq. Cryst. 1996, 283, 31 – 35.

14. Marcus, A. H.; Lin, B.; Rice, S. A. “Self-Diffusion in Dilute Quasi-Two-Dimensional Hard Sphere Suspensions: Evanescent Wave Dynamic Light Scattering and Video Microscopy Studies,” Phys. Rev. E 1996, 53, 1765 – 1776.

15. Marcus, A. H.; Rice, S. A. “Observation of First Order Liquid-to-Hexatic and Hexatic-to-Solid Phase Transitions in a Confined Colloid Suspension,” Phys. Rev. Lett. 1996, 77, 2577 – 2580.

16. Schofield, J.; Marcus, A. H.; Rice, S. A. “The Dynamics of Quasi-Two-Dimensional Colloidal Systems,” J. Phys. Chem. 1996, 100, 18950 – 18961.

17. Marcus, A. H.; Rice, S. A. “Phase Transitions in a Confined Quasi-Two-Dimensional Colloid Suspension,” Phys. Rev. E 1997, 55, 637 – 656.

18. Tam, M. C.-M.; Rice, S. A.; Marcus, A. H. “Unusual Structure in a Quasi-Two-Dimensional Binary Colloidal Fluid,” Chem. Phys. Lett. 1998, 294, 217 – 222.

19. Marcus, A. H.; Schofield, J.; Rice, S. A. “Experimental Observations of Non-Gaussian Behavior and String-like Cooperative Dynamics in Concentrated Quasi-Two-Dimensional Colloidal Liquids,” Phys. Rev. E 1999, 60, 5725 – 5736. See also Marcus, A. H.; Schofield, J.; Rice, S. A. “Erratum: Experimental Observations of Non-Gaussian Behavior and String-like Cooperative Dynamics in Concentrated Quasi-Two-Dimensional Colloidal Liquids,” Phys. Rev. E 1999, 61, 7260 (correction due to byline error).

20. Margineantu, D.; Capaldi, R. A.; Marcus, A. H. “Dynamics of the Mitochondrial Reticulum in Live Cells using Fourier Imaging Correlation Spectroscopy and Digital Video Microscopy,” Biophys. J. 2000, 79, 1833 – 1849 (journal cover article). See also Schurr, J. M. “Molecular Motions in Fourier Transform Space,” Biophys. J. 2000, 79, 1692 – 1694 (editorial comment).

21. Knowles, M. K.; Grassman, T. J.; Marcus, A. H. “Measurement of the Dynamic Structure Function of Fluorescently Labeled Complex Fluids by Fourier Imaging Correlation Spectroscopy,” Phys. Rev. Lett. 2000, 85, 2837 – 2840.

22. Grassman, T. J.; Knowles, M. K.; Marcus, A. H. “Structure and Dynamics of Fluorescently Labeled Complex Fluids by Fourier Imaging Correlation Spectroscopy,” Phys. Rev. E 2000, 62, 8245 – 8257.

23. Margineantu, D.; Brown, R. M.; Brown, G. K.; Marcus, A. H.; Capaldi, R. A. “Heterogeneous Distribution of Pyruvate Dehydrogenase in the Matrix of Mitochondria,” Mitochondrion 2001, 1, 327 – 338.

24. Knowles, M. K.; Margineantu, D.; Capaldi, R. A.; Marcus, A. H. “Translational Dynamics of Fluorescently Labeled Species by Fourier Imaging Correlation Spectroscopy,” in Liquid Dynamics: Experiment, Simulation, and Theory. Pgs. 58 – 70. ACS Symposium Series 820 (American Chemical Society: Washington DC, 2002)

25. Knowles, M. K.; Guenza, M. G.; Capaldi, R. A.; Marcus, A. H. “Cytoskeletal-Assisted Dynamics of the Mitochondrial Reticulum in Living Cells,” Proc. Nat. Acad. Sci. 2002, 99, 14772 – 14777.

26. M.K.Knowles, M.G.Guenza, R.A.Capaldi, A.H.Marcus "Cytoskeletal-assisted dynamics of the mitochondrial reticulum in living cells" Proc. Nat. Acad. Sci. 99, 14772-14777 2002.

27. Capaldi, R. A., R. Aggeler, R. Gilkerson, G. Hanson, M. Knowles, A. Marcus, D. Margineantu, M. Marusich, J. Murray, D. Oglesbee, S. J. Remington, and R. Rossignol, “A replicating module as the unit of mitochondrial structure and functioning.” Biochim. Biophys. Acta: Bioenergetics, 2002, 1555, 192-195.

28. Knowles, M. K.; Honerkamp-Smith, A. R.; Marcus, A. H. “Direct Measurement of the Relative and Collective Diffusion in a Dilute Binary Suspension of Colloidal Particles,” J. Chem. Phys. 2005, 122, 234909-1-13.

29. Fink, M. C.; Adair, K. V.; Guenza, M. G.; Marcus, A. H. “Translational Diffusion of Fluorescent Proteins by Molecular Fourier Imaging Correlation Spectroscopy,” Biophys. J. 2006, Volume 91, 3482-3498.

30.Tekavec, P.F.; Dyke, T.M.; Marcus, A. H. “Wave Packet Interferometry and Quantum State Reconstruction by Acousto-Optic Phase Modulation,” J. Chem. Phys. 2006, 125, 194303-1-19. Selected for publication in the December 2006 issue of the Virtual Journal of Ultrafast Science www.vjultrafast.org.

31. Tekavec, P.F.; Lott, G.A.; Marcus, A.H., "Fluorescence-detected two-dimensional electronic coherence spectroscopy by acousto-optic phase modulation," J. Chem. Phys. 127, 214307 (2007).

32. Goulding, M. B., J. C. Canman, E. N. Senning, A. H. Marcus, and B. Bowerman, "Control of nuclear centration in the C. elegans zygote by receptor-independent Galpha signaling and myosin II," J. Cell Biol. 178, 1177 (2007).