Wolfgang Baumeister was named the winner of the 53rd Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research in 2023 for his pioneering work on the development of a microscopy technique called Cryo-electron tomography. Baumeister is an emeritus Director and Scientific Member of the Max Planck Institute of Biochemistry in Martinsried, Germany where he led a research group on molecular structural biology research. On April 18, 2024, Baumeister delivered his keynote award lecture on his research on improving the functionality of Cryo-Electron Tomography and uncovering structural properties of the proteasome complex 26S.
Abraham and Etta Goodman Professor of Biology and Director of the Rosenstiel Basic Medical Sciences Research Center James Haber introduced Baumeister at the lecture. Haber described the motivation of pursuing novel microscopy techniques for biological and medical applications, saying, “People have long been interested in the limits of vision.” Microscopy is a fundamental tool for biologists as it allows scientists to characterize the localization and dynamics of molecular and structural components. Therefore, finding breakthroughs for improved resolution without compromising sample integrity is an active field of research.
Cryo-electron tomography is a technique that utilizes the vitrification, or exposure to cryogenic temperatures (less than 150 degrees Celsius), of samples in order to achieve near-atomic resolution. Using electron microscopy, samples are imaged at different angles in order to produce a 3D image of the sample surface. Over the last few decades, Baumeister has refined the process of cryo-electron tomography to prevent excess radiative exposure to the sample and mitigate sample compression, both of which are detrimental to image quality. Focused Ion Beam Scanning Electron Microscopy is utilized to prevent the compression of samples and facilitate the imaging of different depths of thick cellular samples. In addition, Baumeister utilized an in-focus Volta Phase Plate in order to achieve better contrast of the images.
Many protein complexes in cellular contexts are subject to quick degradation and are not stable enough to be studied using traditional microscopy techniques. Baumeister’s group studies 26S, a protein complex responsible for protein breakdown in cells. This protein complex is often not suitable for traditional microscopy or biochemical preparations due to its instability. By shock-freezing samples in their true form, cryo-electron tomography has enabled the study of 26S and has revealed novel protein states that this complex may adopt.
Baumeister concluded his talk with ideas for the future of cryo-electron tomography. Over the decades the throughput of this technique has improved dramatically, differing from the order of hours to minutes. In the future, it is likely that imaging will decrease even more. Brandeis has bought a Cryo-Transmission Electron Microscope that will be implemented for research purposes in the summer of 2024. The Rosenstiel Lecture brought together scientists from numerous disciplines that may now be able to apply the discussed techniques for their own research questions through developments in the Brandeis microscopy core.
