department of pharmacology

Taylor Laboratory

Cryo-Electron Microscopy


Microscope


courtesy of W. Baumeister's group

Structural biology has become instrumental to understanding the cellular mechanism of biological complexes. The three-dimensional structures contribute significantly to an understanding of the interactions between the various constituents of multi-component complexes, as well the characterization of their interactions with natural substrates. This fundamental knowledge can then be used to design novel therapeutics designed specifically to disrupt aberrant assembly pathways or to block binding of a harmful ligand. Electron microscopy (EM) has become an invaluable tool for analyzing the structure and molecular interactions of such assemblies. My lab specializes in electron microscopy techniques, which we use to investigate the role of macromolecular complexes in regulating critical functions in cell biology. The structural data are complemented with biochemical and biophysical approaches. EM has gained significant momentum over the past decade as a structural tool for visualizing large molecular machines, particularly because multi-component complexes are extremely difficult, if not impossible, to crystallize for structural studies using X-ray diffraction. Instead of growing crystals, cryo-EM is used to trap a complex in vitreous ice in its most native environment. The cryo-EM reconstruction can then be fitted with atomic models of individual components. This hybrid technique provides a quasi-atomic structure of the entire complex and allows more accurate predictions of the molecular mechanisms.