Bridging the imaging gap in nanobiology with three-dimensional electron microscopy

Summary form only given. Emerging methods in three-dimensional biological electron microscopy provide powerful tools and great promise to bridge a critical gap in imaging in the biomedical size spectrum. This gap comprises a size range of great interest in biology and medicine that includes cellular protein machines, giant protein and nucleic acid assemblies, small subcellular organelles and small bacteria. In our laboratory at the National Cancer Institute, NIH, we are using a variety of approaches that utilize electron microscopic imaging to discover and analyze biological complexity within the size gap with linear dimensions of about 50-1000 nm. A key mission of our laboratory is to quantitatively describe the spatial and temporal architecture of key molecular machines that fall into this "nano gap". Areas of current interest include: (i) the development and application of novel technologies for three-dimensional electron microscopy of specimens ranging in size from small molecules to tissues, including automated approaches to analyze the molecular structure and sub-cellular location of a variety of nanoparticles, (ii) determination of the dynamic spatial and temporal architectures of cellular structures and molecular machines involved in fundamental process such as energy transduction, cell division and chemotaxis, and (iii) determination of molecular mechanisms underlying the neutralization and cellular entry of HIV