Department of Biology
University of California, San Diego
Sanjay earned his bachelors degree at UC Berkeley and spent a year purifying and crystallizing the biotin operon repressor, birA. This was the first protein to be crystallized that is both an enzyme and a transcriptional self-regulator. He joined the Rome lab in 1988 to work on vaults for his doctoral dissertation. Sanjay set up a model system in Dictyostelium discoideum to ask what role the major vault protein (MVP) plays in vault structure and function.
The natural abundance of vaults in Dictyostelium suggested a critical function for the organelle in this organism. Sanjay isolated cDNA's for the two MVP's and used them to generate cell lines containing disruptions in one or both MVP's. Vaults lacking either or both MVP's exhibited a drastically altered morphology. Strikingly, the double mutant exhibited a growth defect phenotype and the presence of yet a third MVP, C. The Dicty MVPA and MVPB represent the first cloned major vault proteins and provided key sequence information for the isolation of MVP's from other species.
Sanjay was drawn to the lab of Dr. Douglass Forbes at UCSD to examine a potential role for vaults at the nuclear pore complex (NPC), a large gateway spanning the nuclear membrane which regulates nucleocytoplasmic transport. He is currently investigating key players in NPC function. To this end, he has mapped functional domains within Nup98, a key nucleoporin implicated in export. His work has identified an export factor binding site as well as a domain which tethers Nup98 within the nucleus. Recently, he has uncovered an interaction between Nup98 and a complex of four large nuclear pore proteins. This complex includes novel proteins as well as proteins implicated in nuclear export. Sanjay's work has linked three separate RNA export complexes, a sizable chunk of the export machinery, and made great headway in mapping a large subdomain of the nuclear basket. He is currently following up additional novel protein-protein interactions involving Nup98.