With the ultimate goal of rapid, automated determination of molecular structures at atomic resolution from as few as a thousand molecules, my group has pioneered the development of new methods in electron diffraction. Using these methods, we interrogate the atomic structure of varied molecular crystals. Equipped with a 300 KeV electron microscope, we are in the unique position to implement a collective suite of methods that explore the limits of electron diffraction on a single dedicated instrument. To achieve this goal, we aim to illuminate clusters of molecules with electron nanobeams. We will measure the resulting diffraction using direct electron detectors and reduce the measured data with custom algorithms. Collectively our proposed efforts will expedite and expand our capacity to interrogate matter at the nano scale, from heterogeneous mixtures of small molecules or peptides to complex proteinaceous assemblies and multi-component nanostructures.