The Section on Cellular and Supramolecular Structure and Function develops new methods based on electron microscopy and related techniques. Our aim is to expand knowledge about complex biological and disease processes, as well as to characterize morphologically the action of diagnostic markers and therapeutic agents in cells. The nanometer scale of biological electron microscopy lies between the realms of live-cell optical microscopy and atomic-scale structural tools of x-ray crystallography and NMR spectroscopy, both of which—unlike EM—require extraction and purification of cellular components. Our approach also complements cryo_EM of isolated frozen-hydrated supramolecular assemblies, which is difficult to apply to intact eukaryotic cells and tissues. We focus on the development of alternative quantitative imaging modes based on detection of elastic and inelastic electron scattering. Current research in the Section Includes development of techniques for (i) determining the tertiary and quaternary structures of macromolecular assemblies, (ii) visualizing 3D ultrastructure, (iii) mapping the elemental composition of subcellular compartments quantitatively, and (iv) studying bionanoparticles and their interactions with cells. We are applying these methods to structural biology, cellular biology, neurobiology, cancer biology, and nanomedicine.
Our group has been particularly active in developing the techniques of electron energy loss spectroscopy (EELS) and combining it with scanning transmission electron microscopy (STEM) to provide an unprecedented high spatial resolution for nanoanalysis of biological structures. We have devised new methods for quantifying both elemental and chemical information obtained from inelastic electron scattering. Recently, our group has extended the techniques of STEM and energy-filtered electron tomography to obtain three-dimensional structural and compositional information about cellular components.