生命科学与医学奖
2025

2025年度邵逸夫生命科学与医学奖颁予沃尔夫冈・鲍迈斯特 (Wolfgang Baumeister)，以表彰他对于冷冻电子断层成像技术 (cryo-ET) 的开创性研发和应用，该三维可视化成像技术使蛋白质、大分子复合物和细胞间隙等生物样本在自然细胞环境中的存在状态得以呈现。沃尔夫冈・鲍迈斯特是德国马克斯普朗克生物化学研究所荣休所长暨科学会员。

人体细胞拥有数十亿种蛋白质和其他生物成分，这些成分负责维持细胞乃至生物体的生命活动。蛋白质有时单独运作，有时与几个其他蛋白质伙伴协作，有时则在大型多蛋白质复合物中工作，而这些复合物更时常会与其他类型的生物分子 (包括去氧核糖核酸 (DNA)、核糖核酸 (RNA) 和脂质膜等) 相互作用。科学家们已经列出了细胞中各个成分的详细清单。通常，这些生物实体的结构中每个原子及其在蛋白质或多蛋白质复合物中的位置，都是精确已知的。然而，对于绝大多数极具研究价值的重要生物实体，我们的认知完全来自于对其“孤立状态”的研究：这些蛋白质或多蛋白质复合物被纯化后，与其他细胞成分完全分离。但是，这些成分在细胞中既不能也不会单独发挥作用。生命的存在，须依赖生物成分之间恰当的相互作用与集体协同。此外，这些相互作用必须在充满数十亿其他生物成分的密集细胞环境中进行。

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.