We are interested in structural and functional characterization of macromolecular assemblies using three-dimensional cryo-electron microscopy (cryoEM) and biochemical, biophysical methods. Proteins carry out their cellular functions through formation of dynamic multi-protein complexes and macromolecular assemblies. These complexes or machines are usually too large and/or too heterogeneous for structural solution by X-ray crystallography or NMR spectroscopy methods. CryoEM is uniquely poised for structure determination of large complexes and macromolecular assemblies, and their conformational changes to provide structural snapshots along dynamic processes. Our interest is to combine structural information obtained through cryoEM methods, with biochemical, physiological analysis to understand molecular mechanisms of protein complexes and machines. We currently focus on three research areas: (I) Understanding HIV-1 and host cell interactions during the early stages of virus infection; (II) Eliciting 3D architectures of the chemotaxis receptor signaling complexes and their assemblies to understand the molecular mechanism of signal transduction in bacterial chemotaxis; and (III) Technology development to enhance the capability of cryo-electron tomography for 3D architectures of native mammalian cells at different signaling state.