Research Description

We are interested in 1) how nuclei move and 2) how nuclei divide.  The cytoskeleton produces well-defined mechanical forces that position the nucleus during early embryonic development in preparation for asymmetric cell division.  These forces can also damage the nuclear envelope; the nuclear envelope, via lamins and nuclear envelope associated proteins, must resist and engage these mechanical forces to protect genome integrity.  In case of damage, nuclear envelope proteins ensure repair of nuclear membranes to prevent loss of nuclear integrity.  Similarly, during mitosis, the nuclear envelope undergoes reorganization to allow chromosome segregation.   Upon exit from mitosis, nuclear membranes and nuclear membrane associated proteins emerge from the ER to reform a sealed nuclear envelope.  Defects in nuclear envelope dynamics in response to cytoskeletal-derived forces or during nuclear envelope reformation in mitosis can have severe consequences on genome integrity.  Furthermore, genes that encode for nuclear envelope associated proteins are mutated in a large number of genetic disorders called “envelopathies.” Using high resolution quantitative time-lapse imaging in the genetically tractable C. elegans zygote and mammalian cells, we aim to dissect mechanisms that promote nuclear envelope and ER dynamics and ensure genome protection in normal and disease contexts.