CSHL Structural Biology Short Courses in Crystallography & Cryo-Electron Microscopy - ABSTRACT Cold Spring Harbor Laboratory (CSHL)’s world-renowned postgraduate course and workshop program has trained investigators and influenced research in fields ranging from proteomics to yeast biology, from ion channel analysis to high throughput neuroanatomy. This proposal seeks support to continue two advanced postgraduate ~two-week residential courses on complementary techniques in structural biology, X-ray crystallography and cryo-electron microscopy, which together represent twin methodological pillars in the atomic and near-atomic resolution of macromolecular structures and complexes. X-ray crystallography and related methods have been the cornerstone of structural biology for half a century and remain the techniques of choice for atomic resolution understanding of macromolecules and for structure guided drug discovery. CSHL’s Macromolecular Crystallography course was initiated in 1988 and combines laboratory and computational instruction to train course participants in the major techniques used to determine three-dimensional structures. It is designed for scientists with a working knowledge of protein structure and function, but who are new to macromolecular crystallography or who wish to increase their in-depth knowledge of macromolecular crystallography. Alumni of the course, including two alumni who went on to win Nobel prizes, have gone on to make major contributions in their fields. Cryo-electron microscopy (cryo-EM) is an emerging technique in structural biology where the biological sample of interest is prepared under cryogenic (deep-freeze) conditions. The utility of cryo-EM stems from the fact that it allows the observation of specimens that have not been stained or fixed in any way, showing them in their native environment. The resolution of cryo-EM maps is improving steadily, and in recent years near-atomic resolution of some structures had been obtained, including those of viruses, ribosomes, mitochondrial protein complexes, ion channels, and enzyme complexes. CSHL’s course on Cryo-Electron Microscopy was initiated in 2018 and covers 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 preparation, microscope alignment, data collection, image processing, and model building. Both courses will teach participants through extensive hands-on experiments along with lectures and informal discussions on the theory behind the techniques and the latest developments in automating experimental and computational procedures, from world leaders in methods development, taking advantage of the outstanding learning environment of the Laboratory’s course program. Applications are open to a wide range of students including scientists from universities and medical schools, as well as Ph.D. and M.D. scientists from industry, aiming to allow students to learn techniques that can be immediately incorporated into their own research, and also enabling translational approaches including rational drug design. Trainees accepted into the course program will include advanced graduate students, postdoctoral trainees, senior scientists and principal investigators; with 70% coming from US labs.
