Prof. Amnon Harel
I am interested in the structure and function of the cell nucleus, including the nuclear lamina, chromatin organization and nuclear pore complexes. The nuclear pore complex (NPC) is one of the largest and most complex macromolecular assemblies in cells and the only known portal for the exchange of molecules between the nucleus and cytoplasm. Current research in my laboratory focuses on the assembly and function of the vertebrate NPC. The main biological questions we are investigating are: (1) how this intricate supramolecular machine is assembled and integrated into the double membranes surrounding the nucleus; (2) the mechanism for targeting and translocation through the NPC of large cellular cargoes and viruses. Among the specific cargoes we are studying are the capsids of the HSV1 virus and intact proteasome particles. To study these topics we rely on the cell-free nuclear reconstitution assay, derived from amphibian egg extracts. We use a combination of protein biochemistry and cell biology approaches, including different light and electron microscopy techniques. In the past several years we have developed improved methods for field emission scanning electron microscopy (FESEM) of nuclear assembly intermediates and nuclear envelopes. These methods are being applied for direct surface imaging of novel intermediates in the NPC biogenesis pathway and for the visualization of nuclear envelopes and NPCs from mammalian cells.