My group studies molecular machines involved in the assembly and regulation of the actin cytoskeleton at the leading edge of motile cells. Structural characterization of these multimolecular protein complexes is likely to reveal potential mechanisms underlying cell growth, differentiation and migration as well as the role of these interactions in tumor invasion, metastasis and bacterial invasion. In particular, we study the role of Arp2/3 complex in actin filament network assembly, the role of myosin in cell migration, and the role of actin binding proteins in providing a scaffold for cell protrusions and adhesion. We combine various electron cryomicroscopy, image analysis and bioinformatics techniques to extract high-resolution structural information of these large dynamic assemblies in their fully hydrated state. Electron cryomicroscopy is the principal method for solving the structures of large complexes that remain beyond the reach of NMR and x-ray crystallography. Although high-resolution structural approaches provide critical information about individual molecules and complexes, a barrier to progress remains their structural and functional integration at the cellular level. Towards this end we are currently developing techniques and protocols that allows us to image whole cell, in their fully hydrate state, and to use bioinformatics tools, to correlate between the high-resolution structural information motives with the in situ characterization obtained from living cells.