Cryo-electron microscopy (cryo-EM) is a rapidly developing technique in structural biology wherein the biological sample of interest is flash frozen under cryogenic conditions. The utility of cryo-electron microscopy stems from the fact that it allows specimens to be observed under “near-to-native” conditions without the need for staining or fixation. This is in contrast to X-ray crystallography, which requires crystallizing the specimen, which can be a long and challenging process, which often involves the introduction of biomolecules into non-physiological environments that can occasionally lead to functionally irrelevant conformational changes. Cryo-EM is now routinely applied to study the structures of viruses, ribosomes, ion channels, transcription and splicing machinery, and many other protein and nucleo-protein complexes. The spiraling number of publications that incorporate cryo-EM methodologies is evidence of this technique’s importance to the structural community: Since 2017, single particle Cryo-EM has been used to solve the structures of more than 1800 molecules, nearly half of which are resolved to better than 4 Å resolution. The resolution of single particle cryo-EM maps is improving steadily, with recent improvements in processing methodologies yielding structures at better than 2 Å resolution. This powerful technique additionally enables researchers to study the conformational landscape of a biological specimen from a single flash-frozen sample, in order to deduce the mechanism by which it works.
The course will cover the theory, practice, and application of single particle cryo-EM. Participants in the course will learn to perform all steps involved in solving high resolution cryo-EM structures, including sample prep, microscope alignment, data collection, image processing, and model building. Students will have supervised access to CSHL’s Titan Krios and K3 direct electron detector, as well as the Talos L120C. This hands-on course will include lectures by leading experts who will discuss practical and conceptual approaches to structure determination using these techniques, as well as covering a wide range of state-of-the-art applications of cryo-EM in the biological sciences.
Applications are open to individuals at universities and colleges, medical research institutions and industry, both from within the United States and from overseas, and to individuals at any stage in their postgraduate (PI, postdoc, grad student, etc.) career. Applicants must demonstrate that they are committed to applying cryo-electron microscopy directly to their own research, and that they work in an environment where such application is feasible and realistic.
Techniques to be Taught:
- Electron microscope optics and alignment
- Negative stain and cryo-EM sample preparation
- Sample screening and optimization
- Automated single particle data acquisition
- Single particle analysis and 3D reconstruction
- EM density visualization, interpretation, and validation
- Atomic model building and validation
2020 Guest Lecturers Include:
Paul Adams, Lawrence Berkeley Laboratory
Bridget Carragher, New York Structural Biology Center
Michael Cianfrocco, University of Michigan
Frank DiMaio, University of Washington
Matthew Johnson, University of Washington
Alexis Rohou, Genentech
Peter Rosenthal, The Francis Crick Institute
Christopher Russo, MRC Laboratory of Molecular Biology
This course is supported with funds provided by:
Financial aid is available to help offset tuition costs as follows:
Please indicate your eligibility for funding in your financial aid request submitted when you apply to the course. Financial aid requests do not affect selection decisions made by the instructors.
Cost (includes food and housing): $4,080
No fees are due until you have completed the full application process and are accepted into the course. Students accepted into the course should plan to arrive by early evening on March 8 and plan to depart after lunch on March 22.
Before applying, ensure you have:
- Personal statement/essay;
- Letter(s) of recommendation;
- Curriculum vitae/resume;
- Financial aid request (optional).
If you are not ready to fully apply but wish to express interest in applying, receive a reminder two weeks prior to the deadline, and tell us about your financial aid requirements, click below:
For more on this course, read what former trainees said of their experience. Also, be sure to check out our growing online alumni presence.