Our lab is interested in understanding how proteins generate and respond to forces inside of cells, and to figure out how these mechanics contribute to the success of key cellular processes. We have a particular interest in cell division. This is because researchers have identified a majority of the biological 'parts' that are involved, but we do not understand the mechanical rules that dictate how all of these pieces work together to reliably segregate DNA into two new daughter cells.
In research performed in Dr. Forth's post-doctoral lab, the force-dependence of non-motor proteins that bind microtubules and are required for the successful completion of cell division were analyzed. 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 by the cell to help maintain protein localization within active microtubule networks.
Additionally, Dr. Forth 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. In order to explain the data, Dr. Forth also built 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.
The Forth lab will be expanding on these studies to understand how the cell builds the complex machinery needed to divide. We are particularly interested in understanding how ensembles of proteins, which are each only several nanometers big, work together to build structures that are thousands of times their size (microns), and to understand how forces and motions within the cell are regulated.