We are interested in mechanisms of genome maintenance and organization. During interphase, chromosomes are surrounded by the nuclear envelope (NE), separating the nuclear and cytoplasmic compartments of the cell. Exchange of all molecules between the nucleus and the rest of the cell occurs through nuclear pore complexes, which are embedded in the NE. NPCs are not only conduits for nucleo-cytoplasmic trafficking, they also promote many aspects of interphase nuclear function, including gene expression and heterochromatin organization. As mammalian cells divide, the NE breaks down and chromosomes condense to allow their partitioning into daughter cells. Remarkably, NPC proteins (nucleoporins) and other components of the nuclear transport machinery have distinct and important mitotic roles that assure the accurate segregation of chromosomes.
Our current focus is to elucidate the role of nucleoporins, NPC–associated proteins (e.g., the SUMO pathway, spindle checkpoint proteins), and other components of the nuclear transport machinery (e.g., the Ran pathway) throughout the cell cycle. We are interested both in how they maintain nuclear organization during interphase and how they promote chromosome segregation. To address both aspects, we have adapted CRISPR–based degron strategies to the study of these proteins; namely, we have tagged the proteins with auxin-induced degrons (AID), which cause them to be specifically destroyed upon the addition of auxin, a plant hormone. The ultimate goals of our studies are to understand how these pathways enable correct genome organization and accurate chromosome segregation, as well as to discover how their functions are coordinated with each other and with other aspects of cell physiology.