Research

The spindle is a highly dynamic structure that segregates chromosomes during cell division. Even though the overall shape 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 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.

A variety of ideas have been proposed to explain how spindles are organized, including suggestions that 1) soluble signals create a global blueprint for spindle structure, 2) spindle components are positioned by a scaffold (potentially made of stabilized microtubules, other proteins, or non-protein polymers), and 3) local interactions between dynamic microtubules, motors, and other proteins spontaneously arrange microtubules to give rise to spindle structure. The relative importance of these, and other factors, is unknown.

More generally, spindles are steady-state structures that can be composed of tens of thousands of microtubules and hundreds of thousands of motor proteins, so their structure and dynamics must be understood in a statistical sense. However, there is no established framework for predicting the behaviors of such nonequilibrium systems.

We are using and development a variety of quantitative experimental techniques to address these issues. Whenever possible, we interpret our data with theoretical or computational approaches.