The 2,420th Meeting of the Society

February 21, 2020 at 8:00 PM

Powell Auditorium at the Cosmos Club

The Presidents' Lecture

Single-Particle Cryo-Electron Microscopy

Revolutionary Methods for Determining the Structures of Biological Molecules in their Native States

Joachim Frank

Professor of Biochemistry and Molecular Biophysics and of Biological Sciences
Columbia University
Co-Winner of the 2017 Nobel Prize in Chemistry

Sponsored by MWZB

About the Lecture

The aim of Structural Biology is to explain life processes in terms of macromolecular interactions in the cell. These interactions typically involve more than two partners, and can run up to dozens. A full description will need to characterize all structures on the atomic level, and the way these structures change in the process. Because of the crowded environment of the cell, such characterization is presently only possible when the group of interacting molecules (often organized into processive “molecular machines”) is isolated and studied in vitro.

While X-ray crystallography has provided structures of a large number of molecular structures, the need for crystals diffracting to high resolution has severely limited the number of supramolecular assemblies and the range of conformers that can be studied with this technique. Single-particle cryo-electron microscopy is about to fill this gap, allowing functional processes to be studied in great detail without imposing restraints on the structures. There are many examples now for this expansion of Structural Biology toward a full characterization of a functional process.

This presentation will cover concept, history and examples of the present capabilities of single-particle cryo-EM, and its significance for medicine. It will then briefly cover the future prospects, which include the study of short-lived intermediates in a non-equilibrium system by time-resolved techniques, and the characterization of continuous structural changes using data mining from large ensembles of molecule images.

About the Speaker

Joachim Frank is Professor of Biochemistry and Molecular Biophysics, and of Biological Sciences at Columbia University. Previously, he was Professor of Biomedical Sciences in the School of Public Health at SUNY Albany and before that he was Senior Research Fellow at the Wadsworth Center.

Joachim’s research has been on developing techniques of electron microscopy and single-particle reconstruction of biological macromolecules, specializing in mathematical and computational approaches. His research notably led to the development of single particle cryo-electron microscopy, greatly facilitating atomic resolution determination of molecular structures, leading to a revolution in the study of, in particular, structures of very large biological complexes and their dynamics. He was awarded the 2017 Nobel Prize in Chemistry for this work, together with Richard Henderson and Jacques Dubochet.

Among many other honors and awards, in addition to the 2017 Nobel Prize, Joachim was awarded the Franklin Medal for Life Science for his contributions to the development of cryogenic electron microscopy of biological molecules and the study of protein synthesis and the Wiley Prize in Biomedical Sciences with Richard Henderson and Marin van Heel. Joachim is a member of the National Academy of Sciences and of the American Academy of Microbiology, and is a Fellow of the American Academy of Arts and Sciences and of the American Association for the Advancement of Science.

Joachim earned his PhD from the Technical University in Munich.