Eukaryotic cells possess a higher level of spatial organization, which is essential for their physiological functions. Understanding the molecular mechanisms that underlie the spatial organization of cell biology is important in our efforts to regenerate damaged tissues and organs, and the treatment of cancer and neurological disorders that arise from defects in cellular architecture and function.
Our work focuses on the spatial organization of epithelia and neurons, and how these cell types break symmetry to develop apical-basolateral and axon-dendrite compartments, and to move directionally during migration.
Cellular asymmetry is largely enabled and supported by microtubules and actin filaments, which are cytoskeletal polymers with polarized structures and dynamics. Microtubules and actin filaments enable directional transport by molecular motors (kinesins, dynein, myosins) and the formation of protrusive structures, which break local symmetries. In our laboratory, we investigate the molecular mechanisms that regulate the spatial organization and dynamics of the cytoskeleton, and the transport of microtubule motors and their cargos.
We have gained novel insights into the spatial organization of cell biology by studying the septin GTPases. Septins are a family of GTP-binding proteins that associate with cell membranes and the microtubule and actin cytoskeleton. Septins are structurally and evolutionarily related to the small GTPases of the Ras family (e.g., Rho/Rac, Rab, Ran), which are known for their roles in the spatial and temporal regulation of cellular processes. Part small GTPase-like regulators and part cytoskeleton-like polymers, septins assemble into higher order structures that control the localization and interactions of membrane and cytoskeletal proteins.
We hypothesize that septins comprise a regulatory module of spatial organization, which provides a core mechanism for the biogenesis of molecular and cellular asymmetry. Research projects explore this hypothesis in the context of membrane traffic, neuronal morphogenesis and cancer cell migration and invasion.