Cell Nucleus; Microscopy, Fluorescence; Microscopy, Confocal; Cellular Structures
Visualizing 3D structure and dynamics at the molecular scale is a current and critical need in biomedical research. Many sub-cellular features, for example the morphology of many organelles or the 3D organization of chromatin, cannot be resolved by standard light microscopy.
Improving the resolution of light microscopy has therefore been an urgent need of biological research for many decades. Today, several methods achieve sub-100 nm resolution by taking advantage of reversible or irreversible photo-physical switching properties of fluorescent markers.
Our research group in the Department of Cell Biology at Yale University School of Medicine is developing new fluorescence microscopy techniques with spatial and/or temporal resolutions exceeding far beyond current technology and also applying them to a diverse set of biological questions.
Specialized Terms: Super-resolution fluorescence microscopy
Extensive Research Description
Our laboratory works on both Stimulated Emission Depletion (STED) microscopy and Fluorescence Photoactivation Localization Microscopy (FPALM/PALM/etc.) techniques. We are actively developing to improve the speed, the 3D resolution and the depth penetration of these imaging techniques to expand the application range of super-resolution microscopy. In collaboration with a diverse set of research groups at Yale University and outside, we apply our new instruments to current biomedical questions.
We are currently working on multiple projects to further improve fluorescence imaging technology and applying these cutting-edge techniques to current biological questions.
Ultra-high resolution 3D imaging of whole cells
F. Huang, G. Sirinakis, E.S. Allgeyer, L.K. Schroeder, W.C. Duim, E.B. Kromann, T. Phan, F.E. Rivera-Molina, J.R. Myers, I. Irnov, M. Lessard, Y. Zhang, M.A. Handel, C. Jacobs-Wagner, C.P. Lusk, J.E. Rothman, D.K. Toomre, M.J. Booth, J. Bewersdorf, Cell 166(4): 1028-1040 (2016)
Two-colour live-cell nanoscale imaging of intracellular targets
Bottanelli F, Kromann EB, Allgeyer ES, Erdmann RS, Wood Baguley S, Sirinakis G, Schepartz A, Baddeley D, Toomre DK, Rothman JE, Bewersdorf J., Nat Commun. 2016 Mar 4;7:10778 (2016)
Video-rate nanoscopy using sCMOS camera–specific single-molecule localization algorithms
F. Huang, T.M.P. Hartwich, F.E. Rivera-Molina, Y. Lin, W.C. Duim, J.J. Long, P.D. Uchil, J.R. Myers, M.A. Baird, W. Mothes, M.W. Davidson, D. Toomre, J. Bewersdorf, Nature Methods 10(7): 653-658 (2013)
Optical Nanoscopy: from Acquisition to Analysis
T.J. Gould, S.T. Hess, and J. Bewersdorf, Annu. Rev. Biomed. Eng. 14: 231–254 (2012)
Adaptive Optics Enables 3D STED Microscopy in Aberrating Specimens
T.J. Gould, D. Burke, J. Bewersdorf, M.J. Booth, Opt. Express 20(19): 20998-21009 (2012)
Three-Dimensional Tracking of Single Fluorescent Particles with Submillisecond Temporal Resolution
M.F. Juette and J. Bewersdorf, Nano Lett. 10(11): 4657-4663 (2010)
A New Wave of Cellular Imaging
D. Toomre and J. Bewersdorf, Annu. Rev. Cell Dev. Biol. 26: 285–314 (2010)
Three-dimensional sub-100 nm Resolution Fluorescence Microscopy of Thick Samples
M.F. Juette, T.J. Gould, M.D. Lessard, M.J. Mlodzianoski, B.S. Nagpure, B.T. Bennett, S.T. Hess, J.Bewersdorf, Nature Methods 5(6): 527-529 (2008)
Novel H2AX Chromatin Structures Revealed by 4Pi Microscopy
J. Bewersdorf, B.T. Bennett, K.L. Knight, Proc. Nat. Acad. Sci. 103: 18137-18142 (2006)
Cooperative 4Pi excitation and detection yields 7-fold sharper optical sections in live cell microscopy
H. Gugel, J. Bewersdorf, S. Jakobs, J. Engelhardt, R. Storz and S.W. Hell, Biophys. J. 87: 4146-4152 (2004)
Multifocal Multiphoton Microscopy
J. Bewersdorf, R. Pick and S.W. Hell, Opt. Lett. 23(9): 655-657 (1998)