Single-particle cryogenic-electron microscopy (cryo-EM) has revolutionized structural biology through its ability to tackle and elucidate structures of numerous macromolecular complexes that have previously been impervious to structural studies. Over the last several years, it has become increasingly clear that some inherent advantages in cryo-EM make it more suitable to structural studies of certain macromolecules, especially those that are large, dynamic, difficult to purify, and/or poorly biochemically behaved. Cryo-EM has therefore quickly become a mainstay in structural biology. Core 1 will employ the latest generation tools in single-particle cryo-EM for the purpose of specifically addressing structural questions relevant to the HIVE P50 center. The tools will be used to solve structures of macromolecular complexes that are involved in the HIV lifecycle, including viral replication, integration, assembly, and maturation, and will thus expand the evolving structural knowledge underlying the molecular processes associated with HIV infection. This in turn will broadly facilitate the improvement of antiretroviral therapies and lead to a better understanding of viral resistance. The Cryo-EM core will: provide basic services that will evaluate sample quality and feasibility of high-resolution studies, a service that will be available to all HIVE members; provide advanced expertise in structural biology to jointly drive high-resolution structure determination in collaboration with several key investigators; apply ongoing or novel technical developments to specific projects on a per-need basis. Core 1 will thus be highly interactive within, and an integral part of, the HIVE center and will coordinate with all its investigators to different extents.