Joerg Bewersdorf, PhD
Research & Publications
Biography
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Research Summary
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 fluorescence microscopy methods achieve resolutions about 10 times better than standard light microscopes. Our research group in the Department of Cell Biology at Yale University School of Medicine is developing a range of techniques with spatial and/or temporal resolutions going far beyond current technology. Additionally, our research group applies these techniques to a diverse set of biological questions.
Specialized Terms: Super-resolution fluorescence microscopy
Extensive Research Description
Our laboratory develops super-resolution Stimulated Emission Depletion (STED) microscopy, Single-molecule Localization Microscopy (FPALM/PALM/STORM/DNA-PAINT, etc.) and pan-Expansion Microscopy (pan-ExM) techniques. We are actively developing these methods to improve the capabilities (speed, 3D resolution, robustness, multicolor labeling) of these imaging techniques and thereby expand the application range and impact of super-resolution microscopy. In collaboration with a diverse set of research groups at Yale University and outside, we apply our new techniques to current biomedical questions, in particular related to the endoplasmic reticulum, the Golgi complex, and the cell nucleus.
Coauthors
Research Interests
Cell Nucleus; Endoplasmic Reticulum; Microscopy, Fluorescence; Microscopy, Confocal; Cellular Structures
Selected Publications
- PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infectionXu D, Jiang W, Wu L, Gaudet R, Park E, Su M, Cheppali S, Cheemarla N, Kumar P, Uchil P, Grover J, Foxman E, Brown C, Stansfeld P, Bewersdorf J, Mothes W, Karatekin E, Wilen C, MacMicking J. PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection. Nature 2023, 619: 819-827. PMID: 37438530, PMCID: PMC10371867, DOI: 10.1038/s41586-023-06322-y.
- Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatinPownall M, Miao L, Vejnar C, M'Saad O, Sherrard A, Frederick M, Benitez M, Boswell C, Zaret K, Bewersdorf J, Giraldez A. Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin. Science 2023, 381: 92-100. PMID: 37410825, PMCID: PMC10372697, DOI: 10.1126/science.ade5308.
- Fluorogenic DNA-PAINT for faster, low-background super-resolution imagingChung KKH, Zhang Z, Kidd P, Zhang Y, Williams ND, Rollins B, Yang Y, Lin C, Baddeley D, Bewersdorf J. Fluorogenic DNA-PAINT for faster, low-background super-resolution imaging. Nature Methods 2022, 19: 554-559. PMID: 35501386, PMCID: PMC9133131, DOI: 10.1038/s41592-022-01464-9.
- DMA-tudor interaction modules control the specificity of in vivo condensatesCourchaine EM, Barentine AES, Straube K, Lee DR, Bewersdorf J, Neugebauer KM. DMA-tudor interaction modules control the specificity of in vivo condensates. Cell 2021, 184: 3612-3625.e17. PMID: 34115980, PMCID: PMC8402948, DOI: 10.1016/j.cell.2021.05.008.
- Three-dimensional adaptive optical nanoscopy for thick specimen imaging at sub-50-nm resolutionHao X, Allgeyer ES, Lee DR, Antonello J, Watters K, Gerdes JA, Schroeder LK, Bottanelli F, Zhao J, Kidd P, Lessard MD, Rothman JE, Cooley L, Biederer T, Booth MJ, Bewersdorf J. Three-dimensional adaptive optical nanoscopy for thick specimen imaging at sub-50-nm resolution. Nature Methods 2021, 18: 688-693. PMID: 34059828, PMCID: PMC7610943, DOI: 10.1038/s41592-021-01149-9.
- Implementation of a 4Pi-SMS super-resolution microscopeWang J, Allgeyer ES, Sirinakis G, Zhang Y, Hu K, Lessard MD, Li Y, Diekmann R, Phillips MA, Dobbie IM, Ries J, Booth MJ, Bewersdorf J. Implementation of a 4Pi-SMS super-resolution microscope. Nature Protocols 2020, 16: 677-727. PMID: 33328610, PMCID: PMC9118368, DOI: 10.1038/s41596-020-00428-7.
- Light microscopy of proteins in their ultrastructural contextM’Saad O, Bewersdorf J. Light microscopy of proteins in their ultrastructural context. Nature Communications 2020, 11: 3850. PMID: 32737322, PMCID: PMC7395138, DOI: 10.1038/s41467-020-17523-8.
- An integrated platform for high-throughput nanoscopyBarentine A, Lin Y, Courvan E, Kidd P, Liu M, Balduf L, Phan T, Rivera-Molina F, Grace M, Marin Z, Lessard M, Rios Chen J, Wang S, Neugebauer K, Bewersdorf J, Baddeley D. An integrated platform for high-throughput nanoscopy. Nature Biotechnology 2023, 1-8. PMID: 36914886, PMCID: PMC10497732, DOI: 10.1038/s41587-023-01702-1.
- Single cell in vivo optogenetic stimulation by two-photon excitation fluorescence transferTong L, Han S, Xue Y, Chen M, Chen F, Ke W, Shu Y, Ding N, Bewersdorf J, Zhou Z, Yuan P, Grutzendler J. Single cell in vivo optogenetic stimulation by two-photon excitation fluorescence transfer. IScience 2023, 26: 107857. PMID: 37752954, PMCID: PMC10518705, DOI: 10.1016/j.isci.2023.107857.
- The nanoscale organization of reticulon 4 shapes local endoplasmic reticulum structure in situFuentes L, Marin Z, Tyson J, Baddeley D, Bewersdorf J. The nanoscale organization of reticulon 4 shapes local endoplasmic reticulum structure in situ. Journal Of Cell Biology 2023, 222: e202301112. PMID: 37516910, PMCID: PMC10373298, DOI: 10.1083/jcb.202301112.
- Highly Multiplexed Imaging with Speed and Fluorogenic DNA-PAINTSchueder F, Bewersdorf J. Highly Multiplexed Imaging with Speed and Fluorogenic DNA-PAINT. Microscopy And Microanalysis 2023, 29: 1069-1069. PMID: 37613180, DOI: 10.1093/micmic/ozad067.548.
- Extracting nanoscale membrane morphology from single-molecule localizationsMarin Z, Fuentes L, Bewersdorf J, Baddeley D. Extracting nanoscale membrane morphology from single-molecule localizations. Biophysical Journal 2023, 122: 3022-3030. PMID: 37355772, PMCID: PMC10432223, DOI: 10.1016/j.bpj.2023.06.010.
- Omics goes spatial epigenomicsSchueder F, Bewersdorf J. Omics goes spatial epigenomics. Cell 2022, 185: 4253-4255. PMID: 36368304, DOI: 10.1016/j.cell.2022.10.014.
- A group approach to growing as a principal investigatorGreco V, Politi K, Eisenbarth S, Colón-Ramos D, Giraldez AJ, Bewersdorf J, Berg DN. A group approach to growing as a principal investigator. Current Biology 2022, 32: r498-r504. PMID: 35671717, DOI: 10.1016/j.cub.2022.04.082.
- 3D super-resolution deep-tissue imaging in living miceVelasco MGM, Zhang M, Antonello J, Yuan P, Allgeyer ES, May D, M’Saad O, Kidd P, Barentine AES, Greco V, Grutzendler J, Booth MJ, Bewersdorf J. 3D super-resolution deep-tissue imaging in living mice. Optica 2021, 8: 442-450. PMID: 34239948, PMCID: PMC8243577, DOI: 10.1364/optica.416841.
- Nanoscale subcellular architecture revealed by multicolor three-dimensional salvaged fluorescence imagingZhang Y, Schroeder LK, Lessard MD, Kidd P, Chung J, Song Y, Benedetti L, Li Y, Ries J, Grimm JB, Lavis LD, De Camilli P, Rothman JE, Baddeley D, Bewersdorf J. Nanoscale subcellular architecture revealed by multicolor three-dimensional salvaged fluorescence imaging. Nature Methods 2020, 17: 225-231. PMID: 31907447, PMCID: PMC7028321, DOI: 10.1038/s41592-019-0676-4.
- Dynamic nanoscale morphology of the ER surveyed by STED microscopySchroeder LK, Barentine AES, Merta H, Schweighofer S, Zhang Y, Baddeley D, Bewersdorf J, Bahmanyar S. Dynamic nanoscale morphology of the ER surveyed by STED microscopy. Journal Of Cell Biology 2018, 218: 83-96. PMID: 30442642, PMCID: PMC6314542, DOI: 10.1083/jcb.201809107.
- Assessing photodamage in live-cell STED microscopyKilian N, Goryaynov A, Lessard MD, Hooker G, Toomre D, Rothman JE, Bewersdorf J. Assessing photodamage in live-cell STED microscopy. Nature Methods 2018, 15: 755-756. PMID: 30275592, PMCID: PMC6915835, DOI: 10.1038/s41592-018-0145-5.
- Biological Insight from Super-Resolution Microscopy: What We Can Learn from Localization-Based ImagesBaddeley D, Bewersdorf J. Biological Insight from Super-Resolution Microscopy: What We Can Learn from Localization-Based Images. Annual Review Of Biochemistry 2017, 87: 1-25. PMID: 29272143, DOI: 10.1146/annurev-biochem-060815-014801.
- Visualization and characterization of individual type III protein secretion machines in live bacteriaZhang Y, Lara-Tejero M, Bewersdorf J, Galán JE. Visualization and characterization of individual type III protein secretion machines in live bacteria. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 6098-6103. PMID: 28533372, PMCID: PMC5468683, DOI: 10.1073/pnas.1705823114.
- Ultra-High Resolution 3D Imaging of Whole CellsHuang F, Sirinakis G, Allgeyer ES, Schroeder LK, Duim WC, Kromann EB, Phan T, Rivera-Molina FE, Myers JR, Irnov I, Lessard M, Zhang Y, Handel MA, Jacobs-Wagner C, Lusk CP, Rothman JE, Toomre D, Booth MJ, Bewersdorf J. Ultra-High Resolution 3D Imaging of Whole Cells. Cell 2016, 166: 1028-1040. PMID: 27397506, PMCID: PMC5005454, DOI: 10.1016/j.cell.2016.06.016.
- Two-colour live-cell nanoscale imaging of intracellular targetsBottanelli F, Kromann EB, Allgeyer ES, Erdmann RS, Wood Baguley S, Sirinakis G, Schepartz A, Baddeley D, Toomre DK, Rothman JE, Bewersdorf J. Two-colour live-cell nanoscale imaging of intracellular targets. Nature Communications 2016, 7: 10778. PMID: 26940217, PMCID: PMC4785223, DOI: 10.1038/ncomms10778.
- Video-rate nanoscopy using sCMOS camera–specific single-molecule localization algorithmsHuang F, Hartwich TM, Rivera-Molina FE, Lin Y, Duim WC, Long JJ, Uchil PD, Myers JR, Baird MA, Mothes W, Davidson MW, Toomre D, Bewersdorf J. Video-rate nanoscopy using sCMOS camera–specific single-molecule localization algorithms. Nature Methods 2013, 10: 653-658. PMID: 23708387, PMCID: PMC3696415, DOI: 10.1038/nmeth.2488.
- Three-dimensional sub–100 nm resolution fluorescence microscopy of thick samplesJuette MF, Gould TJ, Lessard MD, Mlodzianoski MJ, Nagpure BS, Bennett BT, Hess ST, Bewersdorf J. Three-dimensional sub–100 nm resolution fluorescence microscopy of thick samples. Nature Methods 2008, 5: 527-529. PMID: 18469823, DOI: 10.1038/nmeth.1211.
- Multifocal multiphoton microscopy.Bewersdorf J, Pick R, Hell SW. Multifocal multiphoton microscopy. Optics Letters 1998, 23: 655-7. PMID: 18087301.