My research interests involve a mixture of (1) development of methodology for structural biology, with a major emphasis on electron microscopy, and (2) applications of this methodology to specific, biological projects. Areas of previous work have included: establishing the extent to which radiation damage limits imaging at high resolution and averaging of noisy images to overcome those limitations; the use of frozen-hydrated specimens to preserve native, hydrated structure and, to a small extent, to improve the degree to which biological macromolecules can tolerate radiation damage; characterization of the resolution-limiting phenomenon of beam-induced movement; and development of software tools for automated particle boxing and other aspects of high-throughput single-particle EM.
Current research focuses on development of three alternative ways to achieve in-focus phase contrast of cryo-EM specimens. One of these uses a microfabricated electrostatic device to apply a 90 degree phase shift to the unscattered electron beam in the electron diffraction pattern. A second scheme uses a focused laser beam to achieve the same goal. The third scheme uses a “tulip-shaped”, opaque feature within the objective aperture to provide single-sideband contrast at low spatial frequencies while retaining the near-optimal phase shift provided by Scherzer defocus at intermediate and high resolution.
Cambie R, Downing KH, Typke D, Glaeser RM, and Jian Jin. (2007) Design of a microfabricated, two-electrode phase-contrast element suitable for electron microscopy. Ultramicroscopy 107: 329-339.
Downing KH and Glaeser RM. (2008) Restoration of weak phase-contrast images recorded with a high degree of defocus: The "twin image" problem associated with CTF correction. Ultramicroscopy. 108, 921-928.
Glaeser RM. (2008) Retrospective: Radiation damage and its associated “Information Limitations.” J Struct Bio, 163, 271-276.
Taylor KA and Glaeser RM. (2008) Retrospective on the early development of cryoelectron microscopy of macromolecules and a prospective on opportunities for the future. J Struct Bio, 163, 214-223.
Danev R, Glaeser RM, and Nagayama K. (2009) Practical factors affecting the performance of a thin-film phase plate for transmission electron microscopy. Ultramicroscopy, 109, 312-325.
Han BG, Dong M, Liu H, Camp L, Geller J, Singer M, Hazen TC, Cho M, Witkowska HE, Ball DA, Typke D, Downing KH, Shatsky M, Brenner SE, Chandonia JM, Biggin M, and Glaeser RM. (2009) Survey of large protein complexes in D. vulgaris reveals great structural diversity. Proceedings of the National Academy of Sciences USA, 106,16580-16585.
Mueller H, Jin J, Danev J, Spence H, Padmore H, and Glaeser RM. (2010) Design of an electron microscope phase plate using a focused continuous-wave laser. New Journal of Physics, 12, 073011.
Glaeser RM, McMullan, G, Faruqi, AR, and Henderson, R. (2011) Images of paraffin monolayer crystals with perfect contrast: minimization of beam-induced specimen movement. Ultramicroscopy, 111, 90-100.
Glaeser RM, Typke D, Tiemeijer PC, Pulokas J and Cheng, A. (2011) Precise beam-tilt alignment and collimation are required to minimize the phase error associated with coma in high-resolution cryo-EM. J Struct Bio, 174, 1-10.
Glaeser RM and Hall, RJ. (2011) Reaching the information limit in cryo-EM of biological macromolecules. Biophys J, 100,2331-2337.
Hall RJ, Nogales E and Glaeser RM. (2011) Accurate modeling of single-particle cryo-EM images quantitates the benefits expected from using Zernike phase contrast. J Struct Bio, 174, 468-475.
Arbelaez P, Han BG, Typke, D, Lim J, Glaeser RM, and Malik J. (2011) Experimental evaluation of support vector machine-based and correlation-based approaches to automatic particle selection. J Struct Bio, 175, 319-328.
Buijsse B, van Laarhoven MHM, Schmid AK, Cambie R, Cabrini S, Jin J, and Glaeser, RM. (2011) Design of a hybrid double-sideband/single-sideband (schlieren) objective aperture suitable for electron microscopy. Ultramicroscopy, 111, 1688-1695.
Han BG, Walton RW, Song A, Hwu P, Stubbs MT, Yannone SM, Arbelaez P, Dong M, and Glaeser RM. (2012) Electron microscopy of biotinylated protein complexes bound to streptavidin monolayer crystals. J Struct Bio, 180, 249-253.
Grob P, Bean D, Typke D, Li X, Nogales E, and Glaeser RM. (2013) Ranking TEM cameras by their response to electron shot noise. Ultramicroscopy, 133, 1-7.
Glaeser RM, Sassolini S, Cambie R, Jin J, Cabrini S, Schmid AK, Danev R, Buijsee B, Csencsits R, Downing KH, Larson DM, Typke D, and Han BG. (2013) Minimizing electrostatic charging of an aperture used to produce in-focus phase contrast in the TEM. Ultramicroscopy, 135, 6-15.
Glaeser RM. (2013) Invited Review Article: Methods for imaging weak-phase objects in electron microscopy. Rev. Sci. Instrum., 84, 111101.