生命科學與醫學獎
2025

2025年度邵逸夫生命科學與醫學獎頒予沃爾夫岡・鮑邁斯特 (Wolfgang Baumeister)，以表彰他對於冷凍電子斷層成像技術 (cryo-ET) 的開創性研發和應用，該三維可視化成像技術使蛋白質、大分子複合物和細胞間隙等生物樣本在自然細胞環境中的存在狀態得以呈現。沃爾夫岡・鮑邁斯特是德國馬克斯普朗克生物化學研究所榮休所長暨科學會員。

人體細胞擁有數十億種蛋白質和其他生物成分，這些成分負責維持細胞乃至生物體的生命活動。蛋白質有時單獨運作，有時與幾個其他蛋白質夥伴協作，有時則在大型多蛋白質複合物中工作，而這些複合物更時常會與其他類型的生物分子 (包括去氧核糖核酸 (DNA)、核糖核酸 (RNA) 和脂質膜等) 相互作用。科學家們已經列出了細胞中各個成分的詳細清單。通常，這些生物實體的結構中每個原子及其在蛋白質或多蛋白質複合物中的位置，都是精確已知的。然而，對於絕大多數極具研究價值的重要生物實體，我們的認知完全來自於對其「孤立狀態」的研究：這些蛋白質或多蛋白質複合物被純化後，與其他細胞成分完全分離。但是，這些成分在細胞中既不能也不會單獨發揮作用。生命的存在，須依賴生物成分之間恰當的相互作用與集體協同。此外，這些相互作用必須在充滿數十億其他生物成分的密集細胞環境中進行。

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.