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College Affiliation
Emmanuel College
Undergraduate Admissions for Emmanuel College
Graduate Studies Prospectus at Emmanuel College

Research
Publications

Lab Members


Mr. Daniel Duzdevich
Ms. Kelly Neaves


Click here for details of atomic force microscopy (including current projects and publications) in the Department of Pharmacology

 

up image Structure and function of biological macromolecules examined using the atomic force microscope

* Work in this laboratory involves the use of several techniques to investigate the properties of ion channels, transporters, other membrane proteins and nucleic acids at the molecular level.

* The major thrust of the laboratory is the use of the atomic force microscope (AFM) in conjunction with molecular biology techniques to investigate the structure of molecules and to study and image the nature of interactions of molecules.

* The AFM is an instrument that allows construction of three-dimensional images of biological structures at higher resolution than can be obtained using the electron microscope and it has the important advantage that molecules can be studied in real-time under near-physiological conditions.

* Besides providing images it can also produce information on the strength of interactions between molecules under these near-physiological conditions

* Changes in the structure of molecules in response to physiological stimuli can thus be observed as they occur.

3 Images

up image Publications

  • HENDERSON, R. M., SCHNEIDER, S., LI, Q., HORNBY, D., WHITE, S. J. & OBERLEITHNER, H. (1996). Imaging ROMK1 inwardly-rectifying ATP-sensitive K+ channel using atomic force microscopy. Proceedings of the National Academy of Sciences of the United States of America 93, 8756-8760.
  • OBERLEITHNER, H., SCHNEIDER, S., LfRMER, J. & HENDERSON, R. M. (1996). Viewing the renal epithelium with the atomic force microscope. Kidney and Blood Pressure Research 19, 142-147.
  • HENDERSON, R. M. (1997). High resolution imaging of biological macromolecules using the atomic force microscope. Experimental Nephrology 5, 453-456.
  • OBERLEITHNER, H., GEIBEL, J., GUGGINO, W., HENDERSON, R. M., HUNTER, M., SCHNEIDER, S. W., SCHWAB, A. & WANG, W. (1997). Life on biomembranes viewed with the atomic force microscope. Wiener Klinische Wochenschrift 109, 419-423.
  • OBERLEITHNER, H., SCHNEIDER, S. W. & HENDERSON, R. M. (1997). Structural activity of a cloned potassium channel (ROMK1) monitored with the atomic force microscope: The "molecular-sandwich" technique. Proceedings of the National Academy of Sciences of the United States of America 94, 14144-14149.
  • SCHNEIDER, S. W., LfRMER, J., HENDERSON, R. M. & OBERLEITHNER, H. (1998). Molecular weights of individual proteins correlate with molecular volumes measured by atomic force microscopy. Pfl?gers Archiv, European Journal of Physiology 435, 362-367.
  • ELLIS, D. J., BERGE, T., EDWARDSON, J. M. & HENDERSON, R. M. (1999). Investigation of protein partnerships using atomic force microscopy. Microscopy Research and Technique 44, 368-377.
  • ELLIS, D. J., DRYDEN, D. T. F., BERGE, T., EDWARDSON, J. M. & HENDERSON, R. M. (1999). Direct observation of DNA translocation and cleavage by the EcoKI endonuclease using atomic force microscopy. Nature Structural Biology 6, 15-17.
  • DRYDEN, D. T. F., DAVIES, G. D., POWELL, L. M., MURRAY, N. E., ELLIS, D. J., BERGE, T., EDWARDSON, J. M., & HENDERSON, R. M. (1999). The assembly of the EcoKI Type I DNA restriction/modification enzyme and its interaction with DNA. Biochemical Society Transactions 27, 691-696.
  • AVERY, J., ELLIS, D. J., LANG, T., HOLROYD, P., RIEDEL, D., HENDERSON, R. M., EDWARDSON, J. M., & JAHN, R. (2000). A cell-free system for regulated exocytosis in PC12 cells. Journal of Cell Biology 48, 317-324.
  • HENDERSON, R. M. & OBERLEITHNER, H.(2000) Pushing, pulling, dragging and vibrating renal epithelia using atomic force microscopy. Am.J.Physiol. Renal Physiol. 278, F689-F701
  • BERGE, T., ELLIS, D.J., DRYDEN, D.T.F., EDWARDSON, J.M. & HENDERSON, R.M. (2000). Translocation-independent dimerization of the EcoKI endonuclease visualized by atomic force microscopy. Biophys.J. 79, 479-484.
  • OBERLEITHNER, H., SCHILLERS, H., SCHNEIDER, S. W., & HENDERSON, R. M. (2001). Nanoarchitecture of plasma membrane visualized with atomic force microscopy. In Ion Channel Localization Methods and Protocols , eds. Lopatin, A. N. & Nichols, C. G., The Humana Press, Inc, Totowa, NJ.
  • WALKINSHAW, M. D., TAYLOR, P., STURROCK, S. S., ATANASIU, C., BERGE, T., HENDERSON, R. M., EDWARDSON, J. M., & DRYDEN, D. T. F. (2002). Structure of ocr from bacteriophage T7, a protein that mimics B-form DNA. Molecular Cell 9, 187-194.
  • NEISH, C. S., MARTIN, I. L., HENDERSON, R. M., & EDWARDSON, J. M. (2002). Direct visualization of ligand-protein interactions using atomic force microscopy. British Journal of Pharmacology 135, 1943-1950.
  • BERGE, T., JENKINS, N. S., HOPKIRK, R. B., WARING, M. J., EDWARDSON, J. M., & HENDERSON, R. M. (2002). Structural perturbations in DNA caused by bis-intercalation of ditercalinium visualised by atomic force microscopy. Nucleic Acids Research 30, 2980-2986.
  • SASLOWSKY, D. E., LAWRENCE, J., REN, X., BROWN, D. A., HENDERSON, R. M., & EDWARDSON, J. M. (2002) Placental alkaline phosphatase is efficiently targeted to rafts in supported lipid bilayers. Journal of Biological Chemistry 277, 26966-26970
  • ELLIS, D. J., SHADAN, S., JAMES, P. S., HENDERSON, R. M., EDWARDSON, J. M., HUTCHINGS, A., & JONES, R. (2002) Post-testicular development of a novel membrane substructure within the equatorial segment of ram, bull, boar and goat spermatozoa as viewed by atomic force microscopy (AFM). Journal of Structural Biology 138, 187-198.
  • GEISSE, N. A., WASLE, B., SASLOWSKY, D. E., HENDERSON, R. M., & EDWARDSON, J. M. (2002) Syncollin homo-oligomers associate with lipid bilayers in the form of doughnut-shaped structures. Journal of Membrane Biology 189, 83-92
  • LAWRENCE, J. C., SASLOWSKY, D. E., EDWARDSON, J. M., & HENDERSON, R. M. (2003) Real-time analysis of the effects of cholesterol on lipid raft behavior using atomic force microscopy. Biophysical Journal 84, 1827-1832
  • BERGE, T., HAKEN, E. L., WARING, M. J., & HENDERSON, R. M. (2003) The binding mode of the DNA bis-intercalator luzopeptin investigated using atomic force microscopy. Journal of Structural Biology 142, 241-246
  • NEISH, C. S., MARTIN, I. L., DAVIES, M., HENDERSON, R. M. & EDWARDSON, J. M. (2003) Atomic force microscopy of ionotropic receptors bearing subunit-specific tags provides a method for determining receptor architecture. Nanotechnology 14, 864-872.
  • HENDERSON, R. M. (2003). Atomic force microscopy in renal physiology. Methods in Molecular Medicine 86, 139-153.
  • SASLOWSKY, D. E., LAWRENCE, J. C., HENDERSON, R. M., & EDWARDSON, J. M. (2003). Syntaxin is efficiently excluded from sphingomyelin-enriched domains in supported lipid bilayers containing cholesterol. Journal of Membrane Biology 194, 153-164.
  • EDWARDSON, J. M. & HENDERSON, R. M. (2004). Atomic force microscopy and drug discovery. Drug Discovery Today 9, 64-71.
  • HENDERSON, R. M., EDWARDSON, J. M., GEISSE, N. A., & SASLOWSKY, D. E. (2004) Lipid rafts: Feeling is believing. News in Physiological Sciences 19, 39-43.
  • GEISSE, N. A., COVER, T. L. HENDERSON, R. M. & EDWARDSON, J. M. (2004) Targeting of Helicobacter pylori vacuolating toxin to lipid raft membrane domains analysed by atomic force microscopy. Biochemical Journal 381, 911-917.
  • GARAVAGLIA M, DOPINTO S, RITTER M, FURST J, SAINO S, GUIZZARDI F, JAKAB M, BAZZINI C, VEZZOLI V, DOSSENA S, RODIGHIERO S, SIRONI C, BOTTA G, MEYER G, HENDERSON R.M., & PAULMICHL M (2004). Membrane thickness changes ion-selectivity of channel-proteins. Cellular Physiology and Biochemistry 14, 231-240.
  • VIRSTEDT J, BERGE T, HENDERSON RM, WARING MJ, & TRAVERS AA (2004). The influence of DNA stiffness upon nucleosome formation.Journal of Structural Biology 148, 66-85.
  • TSENG YD, GE H, WANG X, EDWARDSON JM, WARING MJ, FITZGERALD WJ, & HENDERSON RM (2005). Atomic force microscopy study of the structural effects induced by echinomycin binding to DNA. Journal of Molecular Biology 345, 745-758.=
  • BARRERA NP, ORMOND SJ, HENDERSON RM, MURRELL-LAGNADO RD, & EDWARDSON JM (2005). AFM imaging demonstrates that P2X2 receptors are trimers, but that P2X6 receptor subunits do not oligomerize. Journal of Biological Chemistry 280, 10759-10765
  • ORMOND SJ, BARRERA NP, QURESHI OS, HENDERSON RM, EDWARDSON JM, & MURRELL-LAGNADO RD (2006). An uncharged region within the N terminus of the P2X6 receptor inhibits its assembly and exit from the endoplasmic reticulum. Mol Pharmacol 69, 1692-1700.
  • BARRERA NP, SHAIFTA Y, MCFADZEAN I, WARD JP, HENDERSON RM, & EDWARDSON JM (2007). AFM imaging reveals the tetrameric structure of the TRPC1 channel. Biochem Biophys Res Commun 358, 1086-1090.
  • BARRERA NP, HENDERSON RM, MURRELL-LAGNADO RD, & EDWARDSON JM (2007). The stoichiometry of P2X2/6 receptor heteromers depends on relative subunit expression levels. Biophys J 93, 505-512.
  • CRAMPTON N, YOKOKAWA M, DRYDEN DT, EDWARDSON JM, RAO DN, TAKEYASU K, YOSHIMURA SH, & HENDERSON RM (2007). Fast-scan atomic force microscopy reveals that the type III restriction enzyme EcoP15I is capable of DNA translocation and looping. Proc Natl Acad Sci U S A 104, 12755-12760.
  • CRAMPTON N, ROES S, DRYDEN DT, RAO DN, EDWARDSON JM, & HENDERSON RM (2007). DNA looping and translocation provide an optimal cleavage mechanism for the type III restriction enzymes. EMBO J. 26, 3815-3825.
  • BENNETT AE, LIU J, VAN RD, BLISS D, ARTHOS J, HENDERSON RM, & SUBRAMANIAM S (2007). Cryo electron tomographic analysis of an HIV neutralizing protein and its complex with native viral gp120. J Biol Chem. 282, 27754-27759.
  • BARRERA N.P., BETTS J, YOU H., HENDERSON R.M., MARTIN I.L., DUNN S.M., & EDWARDSON J.M. (2008). Atomic force microscopy reveals the stoichiometry and subunit arrangement of the α4ß3δGABA(A) receptor. Mol Pharmacol 73, 960-967.
  • BARRERA N.P., HENDERSON R.M., & EDWARDSON J.M. (2008). Determination of the architecture of ionotropic receptors using AFM imaging. Pflügers Arch 456, 199-209.
  • CARNALLY S.M., DEV H.S., STEWART A.P., BARRERA N.P., VAN BEMMELEN M.X., SCHILD L., HENDERSON R.M., & EDWARDSON J.M. (2008). Direct visualization of the trimeric structure of the ASIC1a channel, using AFM imaging. Biochem Biophys Res Commun 372, 752-755.
  • SHAHIN V., DATTA D., HUI E., HENDERSON R.M., CHAPMAN E.R., & EDWARDSON J.M. (2008). Synaptotagmin perturbs the structure of phospholipid bilayers. Biochemistry 47, 2143-2152.
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  • NEAVES K.J., COOPER L.P., WHITE J.H., CARNALLY S.M., DRYDEN D.T.F., EDWARDSON J.M., & HENDERSON R.M. (2009). Atomic force microscopy of the EcoKI Type I DNA restriction enzyme bound to DNA shows enzyme dimerization and DNA looping. Nucleic Acids Res 37, 2053-2063.