Joachim Frank – författare

Electron tomography has become a standard technique with applications in cell biology, structural biology, and materials science. This definitive work provides a comprehensive treatment of the mathematical background and working methods of three-dimensional reconstruction from tilt series, with special emphasis on the problems presented by limitations of data collection in the transmission electron microscope. In addition to chapters that are applicable to 3D reconstruction in all fields of science, such as radiological imaging in medicine and electron tomography in materials science, Electron Tomography also focuses on specimen preparation and imaging unique to biological electron microscopy.

This extensively revised second edition updates key contributions on the mathematics of 3D reconstruction, and includes new topics such as automated tomography, frozen sectioning of cells, and the interpretation of density maps through methods of fitting, docking, denoising, and segmentation. Each chapter is a self-contained treatise by a world expert in the author''s field of research, resulting in an indispensable resource and companion for laboratories that practice electron tomography or seek to implement electron tomography as a tool for visualization of cells and cell components.

 Key Features

Cryo-EM, as it is currently practiced in many laboratories, is limited to the visualization of molecules that are in thermal equilibrium at the time before freezing. A further limitation is that the existing software does not fully exploit the information that is contained in the images of large ensembles of molecules in thermal equilibrium. This book is a collection of recent articles by the author, reprinted with introductions, and they mainly describe two novel methods in cryo-EM, one computational and the other experimental that requires the use of a microfluidic device. Both methods have the capacity to shed light on the dynamic behavior of biomolecules. Combined, they greatly expand the range of applications of cryo-EM.

The book describes a successful approach in which, based on cryo-EM data, all states visited by the molecule in thermal equilibrium are mapped by manifold embedding—a method of geometric machine learning—and the energy landscape of the molecule is derived. It also discusses methods and biological results of time-resolved cryo-EM, following a reaction in a non-equilibrium system over a short period of time and resulting in the capture of short-lived states that have been inaccessible by standard methods of cryo-EM.

Cryo-EM, as it is currently practiced in many laboratories, is limited to the visualization of molecules that are in thermal equilibrium at the time before freezing. A further limitation is that the existing software does not fully exploit the information that is contained in the images of large ensembles of molecules in thermal equilibrium. This book is a collection of recent articles by the author, reprinted with introductions, and they mainly describe two novel methods in cryo-EM, one computational and the other experimental that requires the use of a microfluidic device. Both methods have the capacity to shed light on the dynamic behavior of biomolecules. Combined, they greatly expand the range of applications of cryo-EM.

The book describes a successful approach in which, based on cryo-EM data, all states visited by the molecule in thermal equilibrium are mapped by manifold embedding—a method of geometric machine learning—and the energy landscape of the molecule is derived. It also discusses methods and biological results of time-resolved cryo-EM, following a reaction in a non-equilibrium system over a short period of time and resulting in the capture of short-lived states that have been inaccessible by standard methods of cryo-EM.

Approaches to the recovery of three-dimensional information on a biological object, which are often formulated or implemented initially in an intuitive way, are concisely described here based on physical models of the object and the image-formation process. Both three-dimensional electron microscopy and X-ray tomography can be captured in the same mathematical framework, leading to closely-related computational approaches, but the methodologies differ in detail and hence pose different challenges. The editors of this volume, Gabor T. Herman and Joachim Frank, are experts in the respective methodologies and present research at the forefront of biological imaging and structural biology.

Computational Methods for Three-Dimensional Microscopy Reconstruction will serve as a useful resource for scholars interested in the development of computational methods for structural biology and cell biology, particularly in the area of 3D imaging and modeling.