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Advances in Cryo-Correlative Light and Electron Microscopy: Applications for Studying Molecular and Cellular Events

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Abstract

Cryo-correlative light and electron microscopy (Cryo-CLEM) is materializing as a widespread approach amalgamating the advantages of both fluorescence light microscopy (FLM) as well as three dimensional (3D) cryo-electron tomography (cryo-ET) to reveal the ultrastructure of significant target molecules with specific cellular functions. Cryo-CLEM allows imaging of cells by means of fluorescence microscopy exhibiting the location of the destined molecule at high temporal and spatial resolution while cryo-ET is employed to analyze the 3D structure at a molecular resolution in close-to-physiological condition. Present review focuses upon the practical strategies for Cryo-CLEM and recent technical developments that will assist the broad implementation of this technique to investigate and answer questions pertaining to various biological events occurring in the cell.

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Abbreviations

CLEM:

Correlative light and electron microscopy

EM:

Electron microscopy

ET:

Electron tomography

FM:

Fluorescence microscopy

FLM:

Fluorescence light microscopy

3D:

3-Dimensional

HIV:

Human immunodeficiency virus

AIDS:

Acquired immuno deficiency syndrome

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Acknowledgements

We thank Dr. Peijun Zhang for the comments on the construction of cryo-fluorescence sample stage and the studies of cryo-correlative light and electron microscopy. This work was supported by grants from the research program of the Korea Basic Science Institute (grant number D37402), the National Research Council of Science & Technology which is funded by the Korean government (CRC-16-01-KRICT), 2017 Research grant from Kangwon National University (No. 520170496), the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (2018R1D1A1B07045580 to H.S. Jung; NRF-2017M3A9G7072417 to D. Jeoung), and the Next-Generation BioGreen Program (SSAC, PJ013273042018 to H.S. Jung).

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Author notes

  1. Sangmi Jun, Hyun-Joo Ro and Anahita Bharda have contributed equally to this work.

Authors and Affiliations

  1. Drug & Disease Target Team, Korea Basic Science Institute, 162, Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-Si, Chungcheongbuk-do, 28119, South Korea

    Sangmi Jun, Hyun-Joo Ro & Seung Il Kim

  2. Convergent Research Center for Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, South Korea

    Sangmi Jun, Hyun-Joo Ro & Seung Il Kim

  3. Bio-Analytical Science, University of Science & Technology, Daejeon, South Korea

    Sangmi Jun, Hyun-Joo Ro & Seung Il Kim

  4. Department of Biochemistry, College of Natural Sciences, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-Si, Gangwon-do, 200-701, South Korea

    Anahita Bharda, Dooil Jeoung & Hyun Suk Jung

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  1. Sangmi Jun
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Jun, S., Ro, HJ., Bharda, A. et al. Advances in Cryo-Correlative Light and Electron Microscopy: Applications for Studying Molecular and Cellular Events. Protein J 38, 609–615 (2019). https://doi.org/10.1007/s10930-019-09856-1

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