Understanding the role of the nuclear pore complex in undifferentiated cell proliferation and gene gating

PROJECT SUMMARY / ABSTRACT The nuclear envelope (NE), a double-membrane structure surrounding the cell nucleus, and the nuclear pore complex (NPC), the largest protein assembly residing in the NE, together govern paramount cellular processes of the eukaryotic life, spanning chromatin organization, gene expression regulation, nucleocytoplasmic transport, and signal transduction. Our laboratory is committed to studying diverse and novel functions of the NE and NPC using plants as our model organisms. Our emphasis on plants stems from their unique combination of both conserved and distinct NE and NPC-associated mechanisms evolved in response to complex environmental challenges. In this proposal, we aim to leverage an integrated proteomic, molecular, genetic, and bioinformatic approach, to achieve a mechanistic understanding of how PNET1, a newly identified and evolutionarily conserved NPC membrane component, impacts mitotic progression in undifferentiated cells. Concurrently, we seek to elucidate the central role played by the NPC basket protein, GBPL3, in the precise regulation of stress-induced transcriptional reprogramming through the gene gating mechanism. This research endeavor is expected to significantly advance our understanding of fundamental biological principles underlying cell division and the regulation of gene expression occurring at the level of the NPC. Additionally, it may offer potential avenues for therapeutic interventions targeting aberrant mitotic processes in critical human diseases (e.g., cancers) and provide insights into the precise manipulation of gene expression, both in native and engineered biological systems.