Research: Physical aspects of the organization and dynamics of subcellular structures The Needleman laboratory investigates how the cooperative behaviors of molecules give rise to the architecture and dynamics of self-organizing subcellular structures. Our long term goal is to use our knowledge of subcellular structures to quantitatively predict biological behaviors and to determine if there are general principles which govern these nonequilibrium steady-state systems. Our work focuses on studying the spindle, the self-organizing molecular machine that segregates chromosomes during cell division. Even though the overall structure of the spindle can remain unchanged for hours, the molecules that make up the spindle undergo rapid turnover with a half-life of tens of seconds or less, and if the spindle is damaged, or even totally destroyed, it can repair itself. While many of the individual components of the spindle have been studied in detail, it is still unclear how these molecular constituents self-organize into this structure and how this leads to the internal balance of forces that are harnessed to divide the chromosomes. We use a combination of quantitative experiments and theory to study spindle architecture and dynamics. We employ a range of methods from single molecule tracking, to magnetic tweezers, to high resolution fluorescence and polarized light microscopy, complemented by biochemical and genetic perturbations. In addition, we are developing novel forms of fluorescence correlation spectroscopy and new image analysis methods for optical and electron microscopy.
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