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<div>Dear colleagues:</div>
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<div>Every year or so for the last 12 years I have gathered all the new people in my lab together and gone through the basics of cryo-EM with them from Fourier transforms to lens diagrams to sample prep to data collection and finally image processing. I’ve
also taught a segment about cryo-EM in the Biophysical Methods class I give graduate students every year. </div>
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<div>Two years ago Caltech invited me and other faculty to record professionally-produced lectures for our classes and offer them to the world as “MOOCs” (Massive Open Online Courses). I think online classes are revolutionizing the way math and science is
taught, so I liked the idea and did it. I’m calling the class “Getting started in cryoEM”. It starts with the basic anatomy of electron microscopes, an introduction to Fourier transforms, and the principles of image formation. Building upon that foundation,
the class then covers sample preparation issues, data collection strategies, and basic image processing workflows for tomography, single particle analysis, and 2-D crystallography (see the whole course outline below). I think it is an excellent introduction
that will prepare people for real practical training on the microscope or to engage in serious conversations about cryo-EM: a great way to get started for anyone just joining a cryo-EM lab, or anyone who wants to be sure they have the basic concepts down.</div>
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<div>There are 14 hours of lecture total, shot in two different modes: “weatherman-style,” where I am in front of slides, and “tablet,” where I am drawing and writing on a tablet whose display fills the screen. Each module is accompanied by a list of “study
guide” questions. </div>
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<div>The course homepage is <a href="http://cryo-em-course.caltech.edu/">http://cryo-em-course.caltech.edu</a>. This page presents a brief trailer video with a welcome and excerpts from the course, so you can see what it is like, plus links to the outline,
study guide questions, and the lectures, which have been posted now on several platforms including YouTube, iTunes U, and direct download in either HD or SD formats. Each platform has its advantages and disadvantages, as explained on the lecture videos page.</div>
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<div>I used the videos to “flip” my graduate class for the first time last month, asking the students to watch the lectures at home and then spending class times letting them try to answer the study questions with drawings on the board. I liked it. I think
the recorded lectures are actually substantially better than what I can do live, since I make frequent mistakes live and the tablet was much more powerful than a white board. Plus, people can watch the recorded videos double speed!</div>
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<div>I hope some of you will also find the course valuable. Note I have also included on the course webpages links to two other sources of good teaching videos in cryo-EM that I am aware of: the lecture series recorded at the MRC a couple years ago and the
ongoing lectures about specific software packages hosted by the SB Grid. If there are others out there, please let me know and I’ll be happy to link them too.</div>
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<div>As I mention in the videos, please send any and all feedback (especially pointers to anything I may have gotten wrong!) to GettingStartedInCryoEM@gmail.com. In the future I will also be adding homework problems. If any of you have well-designed problems
you like to use in your courses and want to contribute, we could collect a good set together here, and I’ll be sure to credit them to you. </div>
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<div>Cheers and best wishes,</div>
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<div>Grant</div>
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<div><a href="http://cryo-em-course.caltech.edu/">http://cryo-em-course.caltech.edu</a></div>
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<div>Course outline:</div>
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<div><strong>Part 1: Currents, coils, knobs and names: Basic anatomy of the electron microscope</strong></div>
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<p><em>8 modules, ~2 hours tota<strong>l</strong></em></p>
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<li>Electron guns</li><li>EM lenses</li><li>The column, knobs and names</li><li>The sample chamber</li><li>Energy filters</li><li>Detectors</li><li>Vacuum systems</li><li>Summary, safety</li></ul>
<p><strong> Part 2: Fourier transforms and reciprocal space for beginners<br>
</strong><em>6 modules, ~2 hours total</em></p>
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<li>One dimensional waves and sums</li><li>One-dimensional reciprocal space</li><li>Two-dimensional waves and images</li><li>Two-dimensional transforms and filters</li><li>Three-dimensional waves and transforms</li><li>Convolution and cross-correlation</li></ul>
<p><strong> Part 3: Image formation<br>
</strong><em>6 modules, ~3 hours total</em></p>
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<li>Amplitude and phase contrast, scattering</li><li>Wave propagation and phase shifts</li><li>The contrast transfer function</li><li>Defocus and its effects</li><li>Envelopes</li><li>CTF correction</li></ul>
<p><strong>Part 4: Fundamental challenges in biological EM</strong><br>
<em>5 modules, ~1 hour total</em></p>
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<li>Sample prep: Room temperature methods</li><li>Sample prep: Freezing methods</li><li>Sample prep: Grids</li><li>3-D reconstruction</li><li>Dose limitations</li></ul>
<p><strong>Part 5: Tomography</strong><br>
<em>5 modules, ~2 hours total</em></p>
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<li>Introduction to tomography</li><li>Data collection and reconstruction</li><li>Identifying objects of interest</li><li>Limitations</li></ul>
<p><strong>Part 6: Single-particle analysis</strong><br>
<em>6 modules, ~3 hours tota</em>l</p>
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<li>Introduction to single particle analysis</li><li>Special sample prep issues</li><li>Data collection (imaging)</li><li>Reconstruction basics</li><li>Reconstruction: additional topics</li><li>Interpretation and limitations</li></ul>
<p><strong>Part 7: 2-D crystallography</strong><br>
<em>4 modules, ~1 hour total</em></p>
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<li>Introduction to 2-D crystallography and special sample prep issues</li><li>The Fourier transform of a 2-D crystal</li><li>Data collection and reconstruction</li><li>Helical tubes</li></ul>
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<div>--------------------------------------------------------------------------</div>
<div>Grant Jensen</div>
<div>Professor of Biology and Investigator, HHMI</div>
<div>California Institute of Technology, Mail code 114-96</div>
<div>1200 E. California Blvd.</div>
<div>Pasadena, CA 91125</div>
<div>626-395-8827 (phone)</div>
<div>626-395-5730 (fax)</div>
<div>JensenATcaltech.edu</div>
<div>http://www.jensenlab.caltech.edu</div>
<div>office location: 359 Broad (northwest corner of campus)</div>
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<div>Administrative Assistant Karin Mallard </div>
<div>626-395-8893 (phone)</div>
<div>kmallardATcaltech.edu</div>
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