Biological 3D Structures by Cryo-EM: Challenges in Computations and Instruments

By Wen Jiang

Department of Chemistry, Purdue University, West Lafayette, IN

Published on

Abstract

Single particle cryo-EM is revolutionizing structural biology. Many structures of viruses and protein complexes have been determined to 2-4 Å resolutions. While stable structures that can be expressed/purified in large quantities can be solved routinely, the dynamic compositions and conformations of many protein complexes pose serious challenges to current image processing/3D reconstruction algorithms and computing resources. Novel algorithms or computational methods will be needed to overcome these challenges.

While single particle cryo-EM solve the in vitro structures using isolated protein complexes, high resolution in situ structures in the context of cells using electron tomography are the ultimate goal of structural biology. Due to the limited penetration power of current TEMs at 300 kV, the cells are too thick and must be sectioned into thin slices before being imaged with a TEM. Direct imaging of whole cells will require MeV TEM instruments which are too expensive and inaccessible. Novel design of compact TEMs might make it possible to directly image whole cells.

Bio

Wen Jiang Dr. Jiang’s primary appointment is a Professor in the Department of Biological Sciences at Purdue University. He is also the scientific director of the Purdue Cryo-EM Facility. In addition, he has a courtesy appointment in the Department of Chemistry, Purdue University and is a member of the Purdue Center for Cancer Research, Purdue Institute for Drug Discovery, Purdue Institute of Inflammation, Immunology and Infectious Disease (PI4D).

Dr. Jiang received his B.S. degree in Physics from Peking University, M.S. in Biophysics from the Institute of Biophysics, Chinese Academy and Sciences, and Ph.D./Postdoc in Cryo-EM with Prof. Wah Chiu from Baylor College of Medicine

His group's research interests are in structural biology of viruses, large macromolecular complexes, and membrane proteins. The major tool we use is electron cryo-microscopy (cryo-EM), an emerging technique that has seen dramatic progresses and expansion of the field recently. Our research centers around technique development and application of this method, aiming at higher resolution (2-4 Angstrom), higher throughput imaging and 3-D reconstruction, and broader applicability for new target systems and by novice users.

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Cite this work

Researchers should cite this work as follows:

  • Wen Jiang (2019), "Biological 3D Structures by Cryo-EM: Challenges in Computations and Instruments," https://nanohub.org/resources/31540.

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Location

Burton Morgan, Room 129, Purdue University, West Lafayette, IN

Tags

Biological 3D Structures by Cryo-EM: Challenges in Computations and Instruments
  • Biological 3D Structures by Cryo-EM: Challenges in Computations and Instruments 1. Biological 3D Structures by Cr… 0
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  • Microscopy 2. Microscopy 57.657657657657658
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  • Suitable Samples for Cryo-EM 3. Suitable Samples for Cryo-EM 136.00266933600267
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  • 4. "A 3 minute introduction to Cr… 247.64764764764766
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  • 5. "Cryo-EM Is Revolutionizing St… 435.33533533533534
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  • 6. "Cryo-EM Is Revolutionizing St… 565.03169836503173
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  • 2017 Nobel Prize in Chemistry 7. 2017 Nobel Prize in Chemistry 631.83183183183189
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  • Approaching Atomic Resolutions - 2019 8. Approaching Atomic Resolutions… 655.85585585585591
    00:00/00:00
  • Electron Cryo-Microscopy (Cryo-EM) 9. Electron Cryo-Microscopy (Cryo… 739.3727060393727
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  • Determine Orientation by Projection Matching 10. Determine Orientation by Proje… 808.5085085085085
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  • CryoSPARC: Stochastic Gradient Descent 11. CryoSPARC: Stochastic Gradient… 944.04404404404409
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  • Challenges & Opportunities: Dynamic States 12. Challenges & Opportunities: Dy… 1053.6536536536537
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  • Conformation Heterogeneity: 3D Classification 13. Conformation Heterogeneity: 3D… 1168.0680680680682
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  • Conformation Heterogeneity: Multi-body Refinement 14. Conformation Heterogeneity: Mu… 1234.3009676343011
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  • Challenges & Opportunities: Dynamic States 15. Challenges & Opportunities: Dy… 1290.9576242909577
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  • Cryo-EM 16. Cryo-EM "Resolution Revolution… 1530.4304304304305
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  • In Situ Structures By Tomography 17. In Situ Structures By Tomograp… 1842.5425425425426
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  • Cryo-Electron Tomography 18. Cryo-Electron Tomography 1893.1264597931265
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  • MBIR Algorithm 19. MBIR Algorithm 1990.0900900900901
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  • Visual contrast and missing wedge artifacts 20. Visual contrast and missing we… 2008.2415749082416
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  • Cryo-Electron Tomography: Visual Proteomics 21. Cryo-Electron Tomography: Visu… 2111.2112112112113
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  • Untitled: Slide 22 22. Untitled: Slide 22 2179.3793793793793
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  • Rube Goldberg Approach 23. Rube Goldberg Approach 2225.2252252252251
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  • Untitled: Slide 24 24. Untitled: Slide 24 2255.1551551551552
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  • Untitled: Slide 25 25. Untitled: Slide 25 2278.4451117784452
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  • Towards Whole Cell In Situ Structural Biology 26. Towards Whole Cell In Situ Str… 2298.8655321988658
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  • Current Microscopes: Gun 27. Current Microscopes: Gun 2449.7497497497498
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  • Current Microscopes: Lens 28. Current Microscopes: Lens 2521.287954621288
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  • New Microscope Design 29. New Microscope Design 2565.865865865866
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  • Acknowledgments 30. Acknowledgments 2718.9189189189192
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