Cryo-EM single particle analysis is undergoing rapid changes. In this
talk, I will discuss how developments in sensitive and fast direct
electron detectors yield movies with relatively high signal-to-noise
ratios, and how new image processing techniques to deal with
beam-induced motions and structurally heterogeneous samples are now
yielding near-atomic resolution reconstructions for a wide range of
specimens. I will illustrate the potentials of these methods by
highlighting our recent results on various structures of human
gamma-secretase, the intramembrane protease complex responsible for
cleavage of amyloid precursor protein.