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Fundamentals of Cryo-Electron Microscopy (Cryo-EM) and 3D Image Processing in Structural Biology

By Prof. Somnath Dutta   |   IISc Bangalore
Learners enrolled: 70
ABOUT THE COURSE:

Different types of electron microscopies and their applications in biological system. Basic introduction of electron microscopy physics and optics. Principles of image formation, electron scattering, phase contrast, electron–biological specimen interactions, electron diffraction. Sample preparation, imaging, data collection techniques of biomolecules (DNA, Protein, RNA, lipids, DNA-protein, RNA-protein, lipid-protein, RNA-lipid complexes) for negative staining TEM and cryo-electron microscopy. Basic principles and introduction to structure determination using single particle cryo-EM and cryo-electron tomography.

INTENDED AUDIENCE: UG and PG student

PREREQUISITES: No other courses should be done before this can be done. Good knowledge in Mathematics, Physics, Chemistry and Biology.

INDUSTRY SUPPORT:
  • Any pharmaceutical company will be interested about this course.
  • Sun Pharmaceutical Industries Ltd.,
  • Alembic Pharmaceuticals Ltd.,
  • NATCO Pharma Limited,
  • Serum Institute of India Pvt. Ltd., Pune,
  • Mylan Laboratories Limited,
Summary
Course Status : Upcoming
Course Type : Core
Language for course content : English
Duration : 12 weeks
Category :
  • Biological Sciences & Bioengineering
  • Physics
  • Chemistry
  • Biosciences
Credit Points : 3
Level : Undergraduate/Postgraduate
Start Date : 21 Jul 2025
End Date : 10 Oct 2025
Enrollment Ends : 28 Jul 2025
Exam Registration Ends : 15 Aug 2025
Exam Date : 26 Oct 2025 IST
NCrF Level   : 4.5 — 8.0

Note: This exam date is subject to change based on seat availability. You can check final exam date on your hall ticket.


Page Visits



Course layout

Week 1:  Objectives and basic working principles of different types of microscopes, including all the light microscope. Different types of electron microscopies, like SEM, TEM, STEM, HT-TEM and their applications.

Week 2: Basic introduction of electron microscopy physics like electron gun (sources), electromagnetic lenses system.

Week 3: Various types of aberrations of lenses (Spherical aberration, Chromatic aberration, Astigmatism, Coma), resolution limit of the microscope, magnification, and diffraction by electron microscope.

Week 4: Microscope basic vacuum system, and camera (CCD & Direct electron detectors). Principles of image formation, Ray diagram to understand the image formation, Fourier analysis.

Week 5: Contrast Transfer Function and point spread function, electron scattering, phase contrast, electron–specimen interactions, electron diffraction.

Week 6: Study the various advanced sample preparation techniques for TEM. Negative staining TEM analysis of soluble protein, membrane protein, DNA-protein complex, RNA-protein complex, lipid-protein complex, liposome sample preparation and imaging and image analysis. Identify good and bad negative staining images.

Week 7: Cryo-EM sample preparation (grid preparation) using Vitrobot, VitroJet, Chameleon and other techniques; We will learn sample preparation and imaging of soluble protein, membrane protein, DNA-protein, lipidprotein. Sample loading and automatic data collection and data analysis.

Week 8: Sample preparation using ultramicrotomes & cryo-ultramicrotomes-- tissue sample, whole cells, polymer, and nanoparticles.Learn the methodology to transfer the thin sections to transfer to grids and visualize and analyze samples using TEM and cryo-EM.

Week 9: Data collection using cryo-EM. Study ray diagram to understand focus overfocus under focus image collection, importance of defocused data collection/image collection (for 3D reconstruction and only for imaging), electron dose rate, identify good and bad image, understand Signal/Noise ratio.

Week 10: Theoretical, computational and practical aspects of various advanced 3D image processing techniques for all kinds of EM data. Basic understanding of Cross-Correlation and Convolution. Describe whole pipeline of 3D reconstruction and importance of 2D classification, 3D classifications.

Week 11: Basic principle behind 3D reconstruction and reference-free 2D classification, 3D classifications. Resolution and FSC calculation.

Week 12: Cryo-EM map interpretation and data analysis, FSC calculation, validation, molecular rigid-body docking and basic of model building. 

Books and references

  1.  John J. Bozzola and Lonnie D. Russell (1992). Electron Microscopy (Jones & Bartlett Publishers). 
  2.  Ray F. Egerton (2005). Physical Principles of Electron Microscopy: An Introduction to TEM, SEM, and AEM (Springer). 
  3.  Elaine Evelyn Hunter and Malcolm Silver (1993). Practical Electron Microscopy: A Beginner's Illustrated Guide (Cambridge University). 
  4.  Ludwig Reimer and Helmut Kohl (2008). Transmission Electron Microscopy: Physics of Image Formation (Springer). 
  5.  John Kuo (2007). Electron Microscopy: Methods and Protocols (Methods in Molecular Biology) (Humana). 
  6.  Earl J. Kirkland (2014). Advanced Computing in Electron Microscopy (Springer). 
  7.  Gabor T. Herman and Joachim Frank (2014). Computational Methods for Three-Dimensional Microscopy Reconstruction (Birkhäuser Basel). 
  8.  Joachim Frank (2006). Electron Tomography, (New York, Springer). 
  9.  Joachim Frank (2006). Three-Dimensional Electron Microscopy of Macromolecular Assemblies (New York, Oxford U. Press). 
  10.  Joachim Frank (1996). Three-dimensional Electron Microscopy of Macromolecular Assemblies (San Diego, Academic Press).

Instructor bio

Prof. Somnath Dutta

IISc Bangalore
Prof. Somnath Dutta is an Associate Professor at Molecular Biophysics Unit at Indian Institute of Science, Bangalore, India (since 2016) with experience in teaching and research in the area of structural biology and cryo electron microscopy. Several doctoral students, a few post-doctoral fellows, project assistants and EM manager currently constitute my working group for cryo-EM and structural biology laboratory. My group focuses on the structural studies of metabolic enzymes, pore forming toxins, bacterial secretion systems, bacterial efflux pumps and GPCRs using single particle cryo-electron microscopy. We use different biochemical, and biophysical techniques including negative staining electron microscopy and single particle cryo-EM techniques to characterize the conformational dynamics of very small (100 kDa) protein complexes as well as very large biological macromolecules (2.6 MDa). My group has recently published (Nat. Chem. Bio. 2022, Sci. Advs. 2022, J. cell. Bio. 2021, Structure 2021, Nanomaterial 2021, Cell Rep 2019, J Virol 2019, J. Bio. Chem. 2017, Trends Cell Biol 2019, Nature 2019) these research work in high impact journals.

Additionally, I established a state-of-the-art National cryo-EM facility at IISc, Bangalore, India in 2018. Facility is fully functional, which is helping several researchers and scientists from all over India to collect and process cryo-EM data in this facility. Facility consists of Talos Arctica 200 kV cryo TEM, Vitrobot, T12 120 kV TEM, SEM, carbon coater, glow discharger unit and storage-server for cryo-EM data processing.

Course certificate

The course is free to enroll and learn from. But if you want a certificate, you have to register and write the proctored exam conducted by us in person at any of the designated exam centres.
The exam is optional for a fee of Rs 1000/- (Rupees one thousand only).
Date and Time of Exams: October 26, 2025 Morning session 9am to 12 noon; Afternoon Session 2pm to 5pm.
Registration url: Announcements will be made when the registration form is open for registrations.
The online registration form has to be filled and the certification exam fee needs to be paid. More details will be made available when the exam registration form is published. If there are any changes, it will be mentioned then.
Please check the form for more details on the cities where the exams will be held, the conditions you agree to when you fill the form etc.

CRITERIA TO GET A CERTIFICATE

Average assignment score = 25% of average of best 8 assignments out of the total 12 assignments given in the course.
Exam score = 75% of the proctored certification exam score out of 100

Final score = Average assignment score + Exam score

Please note that assignments encompass all types (including quizzes, programming tasks, and essay submissions) available in the specific week.

YOU WILL BE ELIGIBLE FOR A CERTIFICATE ONLY IF AVERAGE ASSIGNMENT SCORE >=10/25 AND EXAM SCORE >= 30/75. If one of the 2 criteria is not met, you will not get the certificate even if the Final score >= 40/100.

Certificate will have your name, photograph and the score in the final exam with the breakup.It will have the logos of NPTEL and IISc Bangalore .It will be e-verifiable at nptel.ac.in/noc.

Only the e-certificate will be made available. Hard copies will not be dispatched.

Once again, thanks for your interest in our online courses and certification. Happy learning.

- NPTEL team


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