When a higher eukaryotic cell divides, nuclei undergo dramatic remodeling ( Prunuske and Ullman, 2006 ; see figure below, where the pore protein POM121 is green).
Disassembly of nuclear envelope involves dispersal of the nuclear membrane as well as solubilization of nuclear pore complexes, which break into small subunits . We are particularly interested in the process by which the nuclear pore and the nuclear envelope are coordinately disassembled and reassembled during cell division. This has led to an interest in how these processes are connected to cell cycle regulation.
One striking phenotype that arises when levels of Nup153 are depleted in mammalian cells is a delay in cytokinesis (Mackay et al., 2009, Mackay et al., 2010b, Mackay and Ullman, 2011). We track this phenotype both with live cell imaging (as further described in a video protocol, Mackay et al, 2010a) and by monitoring midbodies (see figure), which are structures formed between the two daughter cells that organize the final separation of the cells, or abscission. This unexpected finding led us to a new interest in how the role of Nup153 is tied into the timing of midbody resolution, and we found that defects in assembly of the nuclear pore basket trigger an Aurora B mediated abscission checkpoint (Mackay et al., 2010b). We are now interested in elucidating the molecular link that connects defects in basket architecture to Aurora B.
We are also interested in the process of nuclear assembly and how morphological changes in nuclear structure affect nuclear function in the context of cancer (Chow et al., 2012a) and diseases such as progeria.