Our laboratory is interested in understanding how 10 and 30 nm chromatin fibers fold to form interphase and mitotic chromosomes. Experimentally this has been a very difficult problem to investigate due to a number of technical difficulties. A common approach to this level of chromatin organization has been to use protein extraction conditions which experimentally “unravel” the native chromosome architecture. The difficulty with this approach is separating in vitro produced artifacts from remnants of in vivo structure.

As an alternative strategy we are focusing on changes in interphase chromosome structure during cell cycle progression and initiation of transcription or DNA replication, with the goal of identifying intermediates in the pathway of chromosome condensation or decondensation. A key element of this strategy is preserving chromosome structure as close as possible to its in vivo structure while using 3-dimensional light and electron microscopy reconstruction methods to “computationally” unravel native chromosome structure.