Silver: Genome Organization
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Our studies of nuclear organization concern the spatial and temporal relationships between genes and other nuclear structures and their functional significance. We use a combination of genomic strategies and high resolution imaging to unravel these relationships in, for example, response to signaling pathways.
Recent work from our lab has included a genome-wide study of nuclear organization and involves generating a map of loci associated with the nuclear transport machinery at single gene resolution. In doing so, we made discoveries concerning the relationship between gene activation and repression and associations with for example the nuclear pore. In other studies, we have examined the association of the protein degradation machinery with the genome and found a novel mechanism of feedback control. We have also used novel theoretical approaches to build a model for the organziation of the nucleus by merging large data sets genrated from the genome-wide organization data.
Current interests in the lab include studying the dynamic nature of the genome under different growth states, throughout the cell cycle and in response to drugs in development as anti-cancer therapeutics. In doing so, we have expanded our studies into human cells and tissues where we are investigating the changes in nuclear organization that occur in different disease states. Some of this work derives from our collaboration with Myles Brown who studies the estrogen receptor as well as other hormone receptors. With new technologies, we can now define the association of proteins across the entire human genome.
