The Institute of Molecular Biology

Andrew Marcus

Professor of Chemistry
B.A., University of California;
Ph.D., Stanford University
Member of: Institute of Molecular Biology
Materials Science Institute
Office: Klamath Hall Room 109
Telephone: 541-346-4809
Lab: Klamath Hall Room 117
Telephone: 541-346-4638

Research Interests

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).

Ultraviolet femtosecond optical pulses are used to excite analog labeled DNA molecules in solution, and the fluorescence is monitored in a PM-2D FS experiment.

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.

Selected Publications

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," Nucleic Acids Research, 2011 in press.

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 (in press). Available at ArXiv. See recent UofO press release.

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. See recent UofO press release.

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).

Knowles M. K., Honerkamp-Smith A. R., and A. H. Marcus. (2005) Direct measurement of relative and collective diffusion in a dilute binary colloidal suspension. J. Chem. Phys. 2005 Jun 15; 122 (23): 234909

Knowles M.K., M.G. Guenza, R.A. Capaldi, and A.H. Marcus. (2002) Cytoskeletal-assisted dynamics of the mitochondrial reticulum in living cells. PNAS 99:14772-7.

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)

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.

Grassman, T.J., M.K. Knowles, and A.H. Marcus (2000) Structure and Dynamics of Fluorescently Labeled Complex Fluids by Fourier Imaging Correlation Spectroscopy. Physical Review E 62:8245-57.

Knowles, M.K., T.J. Grassman, and A.H. Marcus (2000) Measurement of the Dynamic Structure Function of Fluorescently Labeled Complex Fluids by Fourier Imaging Correlation Spectroscopy. Physical Review Letters 85:2837-40.

Margineantu, D., R.A. Capaldi, and A.H. Marcus (2000) (journal cover article) Dynamics of the Mitochondrial Reticulum Live Cells using Fourier Imaging Correlation Spectroscopy and Digital Video Microscopy. Biophysical J. 79:1833-49.
See also J.M. Schurr (2000) (editorial comment) Molecular Motions in Fourier Transform Space. Biophysical J. 79:1692-4.

Marcus, A.H., J. Schofield, and S.A. Rice (1999) Experimental Observations of Non-Gaussian Behavior and Stringlike Cooperative Dynamics in Concentrated Quasi-Two-Dimensional Colloidal Liquids. Physical Review E 60:5725-36.

Chung-Ming Tam, M., S.A. Rice, and A.H. Marcus (1998) Unusual Structure in a Quasi-Two-Dimensional Binary Colloidal Fluid. Chemical Physics Letters 294:217-22.

Marcus, A.H., and S.A. Rice (1997) Phase Transitions in a Confined Quasi-Two-Dimensional Colloid Suspension. Physical Review E 55:637-56.

Schofield, J., A.H. Marcus, and S.A. Rice (1996) The Dynamics of Quasi-Two-Dimensional Colloidal Systems. Chem. Phys. J. 100:18950-61.

Marcus, A.H., and S.A. Rice (1996) Observation of First Order Liquid-to-Hexatic and Hexatic-to-Solid Phase Transitions in a Confined Colloid Suspension. Physical Review Letters 77:2577-80.

Marcus, A.H., B. Lin, and S.A. Rice (1996) Self-Diffusion in Dilute Quasi-Two-Dimensional Hard Sphere Suspensions: Evanescent Wave Dynamic Light Scattering and Video Microscopy Studies. Physical Review E 53:1765-76.

Marcus, A.H., T. Morkved, H. Jaeger, S.A. Rice, D.M. Hussey, N.A. Diachun, and M.D. Fayer (1996) Chromophore-Rich Nanodomains in Bulk and Ultra Thin Film Polymer Blends. Molecular Crystals and Liquid Crystals 283:31-5.

Leezenberg, P.B., A.H. Marcus, M.D. Fayer, and C.W. Frank (1996) Rotational Dynamics of Naphthalene-Labeled Cross-link Junctions in Poly(dimethylsiloxane) Elastomers. Chem. Phys. J. 100:7646-55.

Marcus, A.H., D.M. Hussey, N.A. Diachun, and M. D. Fayer (1995) Nanodomain Formation in a Liquid Polymer Blend: the Initial Stages of Phase Separation. Chem. Phys. J. 103:8189-201.

Marcus, A.H., M.D. Fayer, and J.G. Curro (1994) Intermolecular Structure in a Single Component Polymer Glass: Towards High Resolution Measurements of the Side Chain Pair Correlation Function. Chem. Phys. J. 100:9156-69.

Diachun, N.A., A.H. Marcus, and M.D. Fayer (1994) Dynamics in Polydimethylsiloxane: The Effect of Solute Polarity. Amer. Chem. Soc. J. 116:1027-32.

Finger, K.U., A.H. Marcus, and M.D. Fayer (1994) Structure of Complex Systems using Electronic Excitation Transport: Theory, Monte Carlo Simulations, and Experiments on Micelle Solutions. Chem. Phys. J. 100:271-86.

Marcus, A.H., N.A. Diachun, and M.D. Fayer (1993) Intermolecular Structure in a Polymer Glass: Electronic Excitation Transfer Studies. Macromolecules 26:3041-8.

Quitevis, E.L., A.H. Marcus, and M.D. Fayer (1993) Dynamics of Ionic Lipophilic Probes in Micelles: Picosecond Fluorescence Depolarization Measurements. Chem. Phys. J. 97:5762-9.

Marcus, A.H., N.A. Diachun, and M.D. Fayer (1992) Electronic Excitation Transfer in Concentrated Micelle Solutions. Chem. Phys. J. 96:8930-7.

Stein, A.D., D.A. Hoffmann, A.H. Marcus, P.B. Leezenberg, C.W. Frank, and M.D. Fayer (1992) Dynamics in Poly(dimethylsiloxane) Melts: Fluorescence Depolarization Measurements of Probe Chromophore Orientational Relaxation. Chem. Phys. J. 96:5255-63.

Marcus, A.H., and M.D. Fayer (1991) Electronic Excitation Transfer in Clustered Chromophore Systems: Calculations of Time-Resolved Observables for Intercluster Transfer. Chem. Phys. J. 94:5622-30.

Marcus, A.H., TF. Molinski, E. Fahy, D.J. Faulkner, C. Xu, and J. Clardy (1989) 5-Isothiocyanatopupukeanane from a Sponge of the Genus Axinyssa. Organic Chem. J. 54:5184.

Zabriskie, T.M., J.A. Klocke, C.M. Ireland, A.H. Marcus, T.F. Molinski, D.J. Faulkner, C. Xu, and J. Clardy (1986) Jaspamide, a Modified Peptide from a Jaspis Sponge, with Insectisidal and Antifungal Activity. Amer. Chem. Soc. J. 108:3123.