Understanding cell biology using cryo-electron microscopy

Abstract

In order to fully understand biological processes, and how they fail in disease, it is vital to obtain structural information for the relevant biological machinery. Notably, it is becoming increasingly apparent that proteins, the key biological players in fundamental biology or disease mechanisms, often adopt multiple conformations or act in complexes with other proteins. These large and/or dynamic systems present a challenge to traditional methods of 3D structural determination as X-Ray crystallography or NMR. In recent years, single particle analysis (SPA) through cryo-EM has emerged as a mainstream structural biology technique, which can determine the 3D structure of proteins and protein complexes at near-atomic resolution. SPA allows determination of molecular details of purified and isolated proteins at near native conditions, albeit without the spatial and functional context of these proteins within the cell. Cryo Electron Tomography (Cryo-ET) fills this gap by visualizing proteins within their functional cellular environments. This allows for observation of their relationships and interactions with other cellular components and holds great promise for cell biology. In Cryo-EM, specimens are rapidly frozen (vitrified) so that their biologically relevant native states are preserved. This technique has transformed the field of structural biology, leading to new insight into numerous biological processes. Senior Scientist with Thermo Fisher Scientific, Natalia de Val, will discuss the latest advances in the SPA and cellular Cryo-ET workflows and will present the latest results in SPA and Tomography. These results will show how the field is changing our understanding of fundamental cell biology.