for his pioneering development and use of cryogenic-electron tomography (cryo-ET), an imaging technique that enables three-dimensional visualisation of biological samples, including proteins, macromolecular complexes, and cellular compartments as they exist in their natural cellular settings.
The Shaw Prize in Life Science and Medicine 2025 is awarded to Wolfgang Baumeister, Director Emeritus and Scientific Member of the Max Planck Institute of Biochemistry, Germany for his pioneering development and use of cryogenic-electron tomography (cryo-ET), an imaging technique that enables three-dimensional visualisation of biological samples, including proteins, macromolecular complexes, and cellular compartments as they exist in their natural cellular settings.
Human cells possess billions of proteins and other biocomponents that do the work to keep cells, and thus organisms, alive. Sometimes proteins work alone, sometimes they work together with a few other protein partners, sometimes proteins work in large multi-protein complexes, and frequently, these complexes act with other types of biomolecules including DNA, RNA, and lipid membranes. Scientists have long lists of the individual components in our cells. Often structures of these biological entities exist with every atom and its placement in the protein or multi-protein complex precisely known. However, for the vast majority of these fascinating and important biological entities, our knowledge stems exclusively from studies of the isolated protein or isolated multi-protein complex that has been purified away from all other cellular components. But, in cells, these components cannot and do not function alone. For life to happen, proper interactions between and collective activity among biocomponents are required. Moreover, these interactions must take place in the context of cells that are crowded with billions of other biocomponents.
Baumeister’s breakthrough is cryo-ET, a technology that enables the study of proteins and molecular machines in their native contexts, that is, in the intact cell. In cryo-ET, biological samples are rapidly frozen at an extremely low temperature ensuring that the cell or tissue organization is preserved. Next, sequential pictures of the sample are captured as it is slowly rotated (tilted) to acquire the multiple perspectives required to compile its 3-dimensional structure. This revolutionary advance in imaging is important because knowing both the structure and location of macromolecular complexes within cells is crucial for understanding their functions in health and disease. Through dogged persistence and vision, Baumeister overcame major hurdles. For example, cryo-ET required that the most probable identity and orientation of a macromolecule be identified in the large amount of data acquired. Doing so was time-consuming and necessitated informed guess work. To surmount this roadblock, Baumeister developed template matching, a computational method that enables researchers to locate and identify the positions and orientations of macromolecular complexes within crowded cellular environments. Template matching works by comparing known structural templates to the data coming from the cryo-ET analyses. The template matching advance improved the accuracy and the automation of cryo-ET. Another major limitation was that cryo-ET could only be applied to very small, very thin specimens, such as viruses, bacteria, and yeast. This constraint meant that all the important and fascinating questions regarding the native biology occurring in cells and tissues of higher organisms were precluded from cryo-ET interrogation. In a Herculean feat, Baumeister and his team perfected the use of focused ion beam milling (FIB milling), a term used in manufacturing processes. Factories use rotating cutting tools called milling cutters to shape items from various materials, including metal, plastic, wood, and composites. FIB milling, when applied to cryo-ET, slices away biological material from the outsides of thick samples, thus making the remaining sections thin enough for cryo-ET analysis. Development of FIB milling transformed the field, making previously inaccessible biology amenable to study.
Wolfgang Baumeister was born in 1946 in Wesseling, Germany and is currently Director Emeritus and Scientific Member of the Max Planck Institute of Biochemistry, Germany, and Distinguished Adjunct Professor at ShanghaiTech University, PRC. He received his Bachelor’s degree in Biology, Chemistry and Physics in 1969 from the University of Bonn, Germany and PhD in Biophysics in 1973 from the Heinrich Heine University Düsseldorf (HHU), Germany. He was a Research Associate in the Department of Biophysics at HHU (1973–1980) and Heisenberg Fellow in the Physics Department of the Cavendish Laboratory at the University of Cambridge, UK (1981–1982). He then joined the Max Planck Institute of Biochemistry where he was successively a Group Leader of Molecular Structural Biology (1983–1987) and Director of Structural Biology (1988–2021). Since 2000, he has also been an Honorary Professor in the Faculty of Physics at the Technical University of Munich, Germany. He joined ShanghaiTech University as Distinguished Adjunct Professor in 2019. He is a member of the German National Academy of Sciences Leopoldina and the US National Academy of Sciences, as well as a fellow of the American Academy of Arts and Sciences.
