I am interested in understanding how forces and torques that result from proteins doing work inside cells contribute to the success of key cellular processes. I am particularly interested in cell division, primarily because we have identified a majority of the biological 'parts' that are involved, but we do not understand the mechanical rules that describe how they all work together to reliably segregate DNA into two new daughter cells.

In my post-doctoral work, I have analyzed the force-dependence of non-motor proteins that bind microtubules and are required for the successful completion of cell division. Single molecule experiments revealed that different proteins experience different magnitudes of frictional forces when moving across microtubules, and these forces depend on the polarity of the filament. These frictional forces can then be harnessed to help maintain protein localization in large and active polymer networks. A nice and clear write-up can be found on the Rockefeller University website. 

CellGraphicalAbstract.jpg

 

I have also studied how the motor protein kinesin-5 works in ensembles to generate both pushing and braking forces when it is crosslinking two microtubules. Using optical trapping combined with TIRF microscopy, our team showed that forces are regulated by a simple geometric feature, namely the length of overlap between two microtubules. I have also developed a robust theoretical framework and performed Monte Carlo numerical simulations to reveal key properties of these motor protein ensembles. Together, these results help us explain how mitotic spindles are organized and function during cell division. You can find out more in this press release from the Rockefeller University website.

Kinesin5_DevCellGraphicalAbstract.png

 

Previously, I worked to develop a technique called 'Angular Optical Trapping' by which torque and force could be simultaneously measured on single biological molecules. We applied this technique to the study of DNA, discovering that DNA dynamically forms loops (termed 'plectonemes') in a manner that depends on both pulling force and torque.

DNA torque sumary.png