Many of the research programs of Northwestern's Biophysics Faculty fall within the realms of Structural Biology, Drug Design, Quantitative and Mechanistic Biology, Computational Biology and Chemical Biology. With over 20 faculty involved in the program and mani inter-laboratory collaborations, a variety of fundamental biological questions are being studied, including:
Nucleic acid structure and function
Mechanisms of gene regulation
Protein and RNA processing in the cell
Intracellular metal trafficking
Molecular mechanisms of viral infection
Mechanisms of macromolecular machines
Membrane protein structure and function
Selected Movies
A selection of movies produced by the Marko lab at Northwestern
are presented below. The movies form the basis for the PNAS
article by Poirier and Marko (2002). Follow this link for
more movies, courtesy the Marko lab.
Extraction of a single mitotic chromosome from a newt cell
in mitosis (link)
Micrococcal
nuclease digestion of a single mitotic chromosome causing the
chromosome to disintegrate into an apparent 'droplet' of chromatin
fragments (link)
Stretching
of a single mitotic chromosome after mild micrococcal nuclease
digestion causing the chromosome to break into islands of dense
chromatin connected by thin fibers (link)
Selected Research Publications
Adams CD, Schnurr B, Marko JF, Reznikoff WS. Pulling apart catalytically active
Tn5 synaptic complexes using magnetic tweezers. J
Mol Biol. 2007 Mar 23;367(2):319-27. Epub 2006 Dec 28.
Focia, P.J., Shepotinovskaya, I.V., Seidler, J.A., and Freymann, D.M. (2004). Heterodimeric GTPase core of the SRP targeting complex. Science 303, 373-377.
Focia, P.J., Gawronski-Salerno, J., Coon, J.S. V, & Freymann, D.M. (2006) 'Structure of a GDPAlF4 complex of the srp gtpases Ffh and FtsY, and identification of a peripheral nucleotide interaction site', J. Mol Biol. 360 631-643.
Godsey, M.H., G. Minasov, L. Shuvalova, J.S. Brunzelle, I.I. Vorontsov, F.
Collart, and W.F. Anderson. The 2.2 Å resolution crystal structure of
a Bacillus cereus Nif3-family protein YqfO, revels a conserved dimetal binding
motif and a regulatory domain. Protein
Science 16:1285-1293 (2007).
Krasilnikov, A.S., Xiao, Y., Pan, T., and Mondragón, A. (2004). Basis for structural diversity in homologous RNAs. Science 306, 104-107.
Kusunoki, H., Minasov, G., MacDonald, R.I. and Mondragón, A. (2004). Independent movement, dimerization and stability of tandem repeats of chicken brain alpha-spectrin. J. Mol. Biol. 344, 495-511.
Lee, J., Burdette, J. E., MacRenaris, K.W., Mustafi, D., Woodruff, T.K., Meade,
T.J., "Rational
Design, Synthesis, and Biological Evaluation of Progesterone-Modified
MRI Contrast Agents." Chemistry & Biology 2007,14, 824-834. [PDF]
Lieberman, R. L.; Rosenzweig, A. C. Crystal structure of a membrane-bound metalloenzyme that catalyses the biological oxidation of methane, Nature 2005, 434, 177-182. Little, T.H., Zhang, Y., Matulis, C.K., Weck, J., Zhang, Z., Ramachandran, A., Mayo, K.E. & Radhakrishnan, I. (2006). Sequence-specific DNA recognition by steroidogenic factor 1: A helix at the C-terminus of the DNA binding domain is necessary for complex stability. Mol. Endocrinol. 20, 831-843.
Liu, H, Chen, X, Focia, PJ, He, XL. Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases. EMBO J. 2007 Feb 7;26(3):891-901.
Major J.L., Parigi G., Luchinat, C., Meade T.J., "The
synthesis and in vitro testing of a zinc-activated MRI contrast
agent." Proc
Natl Acad Sci USA, 2007, 104, 13881-6. [PDF]
Miller, M.T., Bachmann, B.O., Townsend, C.A., and Rosenzweig, A.C. (2002). The catalytic cycle of b-lactam synthetase observed by x-ray crystallographic snapshots. Proceedings of National Academy of Sciences (USA) 99, 14752-14757.
Miller, D.J., L. Shuvalova, E. Evdokimova, A. Savchenko, A.F. Yakunin and
W.F. Anderson. Structural and Biochemical
Characterization of a novel Mn2+-Dependent Phosphodiesterase Encoded
by the yfcE Gene. Protein Science 16:1338-1348 (2007). [PDF]
Olejniczak, M & Uhlenbeck, O.C. (2006). "tRNA residues that have coevolved with their anticodon to ensure uniform and accurate codon recognition." Biochemie 8, 943-50.
Pham, J. W., Pellino, J. L., Lee, Y. S., Carthew, R. W., and Sontheimer, E.
J. (2004). A Dicer-2-Dependent 80S
Complex Cleaves Targeted mRNAs during RNAi in Drosophila. Cell 117, 83-94.
[PDF]
Prakash, S., Tian, L., Ratliff, K.S., Lehotzky, R.E., and Matouschek, A. (2004). An unstructured initiation site is required for efficient proteasome-mediated degradation. Nature Structural & Molecular Biology 11, 830-837.
Preall, J. B., He, Z., Gorra, J., and Sontheimer, E. J. (2006). Short Interfering
RNA Strand Selection is Independent of dsRNA Processing Polarity During
RNAi in Drosophila. Curr. Biol. 16, 530-535. [PDF]
Rajan, S.S., Yang, X., Collart, F., Yip, V.L., Withers, S.G., Varrot, A., Thompson, J., Davies, G.J., and Anderson, W.F. (2004). Novel catalytic mechanism of glycoside hydrolysis based on the structure of an NAD +/Mn 2+-dependent phospho- a-glucosidase from Bacillus subtilis. Structure (Cambridge) 12, 1619-1629.
Ranjith P, Yan J, Marko JF. (2007). Nucleosome hopping and sliding kinetics
determined from dynamics of single chromatin fibers in Xenopus egg extracts. Proc
Natl Acad Sci U S A. 2007 Aug 21;104(34):13649-54. Epub 2007 Aug 14.
Sanderson, L.E. & Uhlenbeck, O.C. (2007). "The 51-63 Base Pair of tRNA Confers Specificity for Binding by EF-Tu". RNA 13. 835-840.
Seo, J.; Igarashi, J.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Structure-Based Design and Synthesis of Nw-Nitro-L-Arginine-Containing Peptidomimetics as Selective Inhibitors of Neuronal Nitric Oxide Synthase. Displacement of the Heme Structural Water. J. Med. Chem. 2007, 50, 2089-2099.
Segal, E., Fondufe-Mittendorf, Y., Chen, L., Thåström, A., Field, Y., Moore, I.K., Wang, J.Z., and Widom, J. (2006), "A Genomic Code for Nucleosome Positioning", Nature 442: 772–778.
Swanson, K.A., Knoepfler, P.S., Huang, K., Kang, R.S., Cowley, S.M., Laherty, C.D., Eisenman, R.N., and Radhakrishnan, I. (2004). HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations. Nature Structural & Molecular Biology 11, 738-746.
Taneja, Bhupesh, Schnurr, Bernhard, Slesarev, Alexei, Marko, John F., and Mondragón,
Alfonso. Topoisomerase V relaxes supercoiled DNA by a constrained swiveling
mechanism. Proc
Natl Acad Sci USA 104, 14670-14675 (2007). Published September 5, 2007, 10.1073/pnas.0701989104
Wang, Z.; Yuan, H.; Silverman, R. B. (±)-(1S,2R,5S)-5-Amino-2-fluorocyclohex-3-ene Carboxylic Acid, A Potent GABA Aminotransferase Inactivator that Irreversibly Inhibits through an Elimination-Aromatization Pathway. Biochemistry, 2006, 45, 14513-14522.
Wehrman, T., He, XL, Raab, B, Dukipatti, A, Blau, H, Garcia, KC. Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors. Neuron. 2007 Jan 4;53(1):25-38
Wiggins, P.A., van der Heijden, T., Moreno-Herrero, F., Spakowitz, A., Phillips, R., Widom, J., Dekker, C., and Nelson, P.C. (2006), Beyond the wormlike chain: High flexibility of DNA on short lengthscales probed by atomic force microscopy, Nature Nanotechnology 1: 137–141.
Yatsunyk, L. A.; Rosenzweig, A. C. Copper binding and transfer by the N-terminus of the Wilson disease protein. J. Biol. Chem. 2007, 282, 8622-8631
