Members & Research

Daniel Needleman uses quantitative experimental techniques to study how the cooperative behaviors of molecules give rise to the architecture and dynamics of self-organizing sub-cellular structures. These collective effects are not only directly relevant to cellular organization, they also raise a number of fascinating questions concerning the mechanics and statistical physics of these highly nonequilibrium systems. His long-term goal is to use the knowledge of sub-cellular structures to quantitatively predict biological behaviors and to determine if there are general principles that govern these nonequilibrium steady-state systems.

Work in the Needleman laboratory currently focuses on studying the spindle, the self-organizing molecular machine that segregates chromosomes during cell division. The spindle is a dynamic steady-state structure composed of a plethora of molecules, most notably DNA, which is compacted into chromosomes, and the protein tubulin, which forms long fibers, called microtubules, which are oriented into a bipolar array that constitutes the bulk of the spindle. 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.
Research in the Needleman laboratory uses three complementary approaches

1) The structure and dynamics of spindles in cells and cell extracts are studied using a range of methods including single molecule tracking, magnetic tweezers, fluorescence correlation spectroscopy, and high resolution fluorescence and polarized light microscopy. Measurements are combined with biochemical and genetic perturbations to relate the underlying protein dynamics to spindle architecture and, finally, chromosome motion. When possible, we attempt to quantitatively interpret our experiments using simple theories and physical ideas.

2) Novel experimental techniques are developed. This includes work on a massively parallel form of fluorescence correlation spectroscopy and new image analysis methods for optical and electron microscopy.

3) Simple model systems of highly purified cytoskeletal components are used to study selected aspects of biological self-organization. Experiments performed on in vitro systems reconstituted from purified components can be highly controlled and therefore provide the ability to test theories in a more rigorous manner than is possible in vivo.