Institute of Molecular Biology

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Andrew Marcus

Andrew Marcus

Professor, Chemistry and Biochemistry
Associate Member, IMB

Ph.D., Stanford University
B.A., University of California

Office: Klamath Hall Room 109
Office Phone: 541-346-4809
Lab: Klamath Hall Room 117
Lab Phone: 541-346-4638

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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.

Recent publications

(pulled from pubmed)

Recent publications

(pulled from pubmed)

Electric Dipole Transition Moments and Solvent-Dependent Interactions of Fluorescent Boron-Nitrogen Substituted Indole Derivatives.
Saif M, Widom JR, Xu S, Abbey ER, Liu SY, Marcus AH
J Phys Chem B 2015 Jun 25;119(25):7985-93
Quantum process tomography by 2D fluorescence spectroscopy.
Pachón LA, Marcus AH, Aspuru-Guzik A
J Chem Phys 2015 Jun 7;142(21):212442
Coherent two-dimensional photocurrent spectroscopy in a PbS quantum dot photocell.
Karki KJ, Widom JR, Seibt J, Moody I, Lonergan MC, Pullerits T, Marcus AH
Nat Commun 2014 Dec 18;5:5869
Electronic transition moments of 6-methyl isoxanthopterin--a fluorescent analogue of the nucleic acid base guanine.
Widom JR, Rappoport D, Perdomo-Ortiz A, Thomsen H, Johnson NP, von Hippel PH, Aspuru-Guzik A, Marcus AH
Nucleic Acids Res 2013 Jan;41(2):995-1004
Temperature-dependent conformations of a membrane supported zinc porphyrin tweezer by 2D fluorescence spectroscopy.
Widom JR, Lee W, Perdomo-Ortiz A, Rappoport D, Molinski TF, Aspuru-Guzik A, Marcus AH
J Phys Chem A 2013 Jul 25;117(29):6171-84
Fifty years of DNA "Breathing": Reflections on old and new approaches.
von Hippel PH, Johnson NP, Marcus AH
Biopolymers 2013 Dec;99(12):923-54
Entangled photon-pair two-dimensional fluorescence spectroscopy (EPP-2DFS).
Raymer MG, Marcus AH, Widom JR, Vitullo DL
J Phys Chem B 2013 Dec 12;117(49):15559-75
Single-molecule FRET and linear dichroism studies of DNA breathing and helicase binding at replication fork junctions.
Phelps C, Lee W, Jose D, von Hippel PH, Marcus AH
Proc Natl Acad Sci U S A 2013 Oct 22;110(43):17320-5
Compressed Sensing for Multidimensional Spectroscopy Experiments.
Sanders JN, Saikin SK, Mostame S, Andrade X, Widom JR, Marcus AH, Aspuru-Guzik A
J Phys Chem Lett 2012 Sep 20;3(18):2697-2702
Conformation of self-assembled porphyrin dimers in liposome vesicles by phase-modulation 2D fluorescence spectroscopy.
Lott GA, Perdomo-Ortiz A, Utterback JK, Widom JR, Aspuru-Guzik A, Marcus AH
Proc Natl Acad Sci U S A 2011 Oct 4;108(40):16521-6
Actin polymerization driven mitochondrial transport in mating S. cerevisiae.
Senning EN, Marcus AH
Proc Natl Acad Sci U S A 2010 Jan 12;107(2):721-5
II. Kinetic pathways of switching optical conformations in DsRed by 2D Fourier imaging correlation spectroscopy.
Senning EN, Lott GA, Fink MC, Marcus AH
J Phys Chem B 2009 May 14;113(19):6854-60
Fourier imaging correlation spectroscopy for cellular structure-function.
Senning EN, Lott GA, Marcus AH
Methods Cell Biol 2008;90:117-37
Control of nuclear centration in the C. elegans zygote by receptor-independent Galpha signaling and myosin II.
Goulding MB, Canman JC, Senning EN, Marcus AH, Bowerman B
J Cell Biol 2007 Sep 24;178(7):1177-91
Translational diffusion of fluorescent proteins by molecular fourier imaging correlation spectroscopy.
Fink MC, Adair KV, Guenza MG, Marcus AH
Biophys J 2006 Nov 1;91(9):3482-98
Wave packet interferometry and quantum state reconstruction by acousto-optic phase modulation.
Tekavec PF, Dyke TR, Marcus AH
J Chem Phys 2006 Nov 21;125(19):194303
Direct measurement of relative and collective diffusion in a dilute binary colloidal suspension.
Knowles MK, Honerkamp-Smith AR, Marcus AH
J Chem Phys 2005 Jun 15;122(23):234909
Cytoskeletal-assisted dynamics of the mitochondrial reticulum in living cells.
Knowles MK, Guenza MG, Capaldi RA, Marcus AH
Proc Natl Acad Sci U S A 2002 Nov 12;99(23):14772-7
Heterogeneous distribution of pyruvate dehydrogenase in the matrix of mitochondria.
Margineantu DH, Brown RM, Brown GK, Marcus AH, Capaldi RA
Mitochondrion 2002 Feb;1(4):327-38
Structure and dynamics of fluorescently labeled complex fluids by fourier imaging correlation spectroscopy
Grassman TJ, Knowles MK, Marcus AH
Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 2000 Dec;62(6 Pt B):8245-57
Experimental observations of non-Gaussian behavior and stringlike cooperative dynamics in concentrated quasi-two-dimensional colloidal liquids.
Marcus AH, Schofield J, Rice SA
Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 1999 Nov;60(5 Pt B):5725-36