Exploring the Capability of Cryo-EM to Provide Insight Beyond Static Structures of Macromolecules

In the past few years, electron cryomicroscopy (cryo-EM) has emerged as an important tool for the analysis of biomolecular structures at resolutions that allow construction of atomic models. However, cryo-EM has the potential to do more than determine molecular structures. Cryotomography can describe cellular morphology at resolutions inaccessible to other techniques. Single particle methods have the potential to explore heterogeneity in macromolecules and time-dependent processes. Hybrid methods can be used study protein structure and organization in the context of living cells.

In the past, methodological development in cryo-EM has been dominated by attempts to improve resolution. These efforts will undoubtedly continue, but now cryo-EM can often reach or exceed the resolution possible with other techniques like X-ray crystallography or NMR spectroscopy, but without the stringent sample requirements of those techniques. This meeting will emphasize the areas of cryo-EM that go beyond what has become the low-hanging fruit of determining structures of stable proteins with single particle cryo-EM. It will look at methods and approaches used for specimen preparation, imaging, and image analysis to allow cryo-EM to solve other problems. We will discuss how cryo-EM is being used and adapted for the discovery of therapeutics and how novel instrumentation, imaging methods, and algorithms are allowing new types of specimens to be studies. As always, we will also look at the capabilities and current limitations of cryo-EM from the perspective of samples that are difficult to work with.