A synthetic nuclear pore complex. Courtesy of Chenxiang Lin.
Keeping the nucleus together
The nucleus houses the genome in an elaborate membrane system called the nuclear envelope, which forms a barrier that segregates the gene expression machinery between the nucleoplasm and cytoplasm. The barrier is established by the nuclear membranes in concert with massive protein assemblies called nuclear pore complexes (NPCs) that control all molecular exchange between these compartments. It is becoming clear that the rupture of the nuclear membranes and/or the disruption of NPC function is a key component of the cellular pathophysiology of many different diseases including cancers and neurodegeneration. Our lab is interested in defining the fundamental molecular mechanisms that lead to the biogenesis and, most importantly, the maintenance of the integrity of the nuclear compartment. For example, we have defined quality control mechanisms that surveil and repair defective NPCs and nuclear membrane ruptures. We are actively pursuing whether these surveillance pathways are perturbed in human diseases and whether they can be leveraged to maintain nuclear integrity in the face of genetic or mechanical perturbation to the nuclear membrane system.