Professor of Biochemistry and Structural Biology Wolfgang Baumeister has been named the 53rd winner of the Rosenstiel Award for Distinguished Work in Basic Medical Research. Baumeister is celebrated for his pioneering work developing a technique called cryo-electron tomography.
To answer research questions at the intersection of biology and chemistry, it is often crucial to be able to visualize cellular and subcellular macromolecules with high resolution. However, there are several biological and technical issues that often make high resolution imaging difficult. Often, molecules of interest are highly unstable, and therefore cannot be purified from biochemical preparations for further studies.
Baumeister is the Director Emeritus and Scientific Member of the Max Planck Institute in Martinsried, Germany. His group’s work has implemented cryo-electron tomography in order to understand the molecular machinery involved in protein degradation and proper protein folding.
One protein complex Baumeister has studied is 26S, which is responsible for proper protein degradation, a process vital for cellular health. Despite the important task 26S plays, it is difficult to study the biochemical properties of this protein complex using traditional methods due to its instability.
Several other technical issues arise in traditional imaging protocol. In electron microscopy, for example, samples are imaged under the conditions of a high vacuum. This is often incompatible with samples from cells, since water will boil off and the pressure differences will cause the cells to explode. To mitigate this, researchers may desiccate cells and chemically fix cellular processes for subsequent imaging. However this may distort subcellular structures, which prevents high resolution imaging.
Furthermore, in transmission electron microscopy, the image is produced by capturing electron-rich matter. However, the resolution is limited by the thickness of the sample, and higher thicknesses can block off the electron beam necessary to discriminate between cellular features.
Cryo-electron tomography solves these issues by preserving cellular samples in cryo condition, that is, below -150 degrees Celsius. Cells are prepared in a standard aqueous solution and then frozen so efficiently that the water molecules are unable to form the crystal lattice structure, and cellular structures are preserved in structure. As conducted in transmission electron microscopy, the image is then tilted to obtain 2D slices, which can then be reconstructed into a 3D shape of the sample. This allows cellular samples to be imaged without the distortion from chemical fixation, and allows imaging of highly unstable species.
Baumeister will deliver his lecture for the Rosenstiel Award on April 18, 2024.