During my Ph.D. research I studied dynein, a protein that uses the chemical energy of ATP to create force and motion. To me the most fascinating thing about dynein is that it can convert chemical energy into mechanical work. Of course many things do this on the macroscopic scale (e.g. gasoline engines, rockets), but doing it as a molecule is really quite impressive. Dynein uses long, rigid filaments called microtubules as a track to move along, transporting important cellular components in the process. Dynein is required for life in humans; defects in dynein driven transport lead to various unpleasant diseases.
I worked in the Yildiz Lab at UC Berkeley, where we built instruments that are sensitive enough to observe single molecules. In addition to observing the molecules, I also had the really neat ability to apply forces to them using the momentum of the photons generated by a powerful laser. I used these instruments to study how dynein creates mechanical work from the chemical energy stored in ATP, and how it can move long distances along its track without detaching. Both of these are truly remarkable properties for a molecule to have, which is part of what makes dynein so interesting to study.
In the course of my thesis research I discovered a lot about how dynein works by changing parts of the motor and studying the effects, some of which were very surprising. Using analysis and modeling in Python and MATLAB, and combining this data with a new type experiment to measure how dynein responds to forces allowed for the development of a detailed model of dynein motility. We also were able to form a hypothesis about why dynein moves in the direction it does. A collaboration with the Carter Lab at the MRC Laboratory of Molecular Biology in Cambridge allowed us to support this hypothesis by engineering a dynein powered motor that moves in the opposite direction, something that had never been observed in the laboratory or in nature.
Cleary et al. Tension on the linker gates the ATP-dependent release of dynein from microtubules Nat. Commun. 2014
My research was supported in part by an NSF Graduate Research Fellowship.