Laminin is a major component of the extracellular matrix (ECM) and arose early in animal evolution. Due to its role in cell adhesion and migration, laminin is central to development and disease. Laminin is a heterotrimer with a total mass of up to 800 kD. Its three subunits (α, β, and γ) assemble into a distinctive cross-shaped structure, copies of which further self-assemble to form a network. Higher organisms contain a number of isotypes of each subunit, which produce, combinatorially, a rich family of related proteins with certain structural and functional distinctions. Many fundamental aspects of laminin structure are understood from rotary shadowing electron microscopy, recognizable amino acid sequence motifs (i.e., coiled-coil heptad repeats), and X-ray crystallography of laminin fragments. However, other conserved portions of laminin, namely the L4, LF, and Lβ knob domains, are still poorly understood, both structurally and functionally. The L4 and LF domains are embedded within the EGF-like repeats that make up the short arms of the laminin cross, whereas the Lβ knob is inserted into the coiled-coil that constitutes the long arm of the cross. Until we determine the structures and functions of these embedded domains, our understanding of laminin and its binding and signaling capabilities will remain incomplete. This research project offers a rotation student the opportunity to work with Ph.D. students in the lab to learn protein purification and X-ray crystallography, as applied to the structures of key segments of laminin. The rotation student would also have the opportunity to be introduced to novel techniques in electron microscopy. Overall, the lab aims to combine a variety of structural and cell biological approaches to advance our understanding of laminin and its relation to other ECM components and to cells.