Physiology & Biophysics
Motion is fundamental to life. Everyone is familiar with the macroscopic motion of muscle contraction. There are also exquisite, essential motions taking place at the level of cells and molecules. The cells in our immune system crawl around our bodies and engulf invading bacteria. Cilia in our lungs beat to remove inhaled debris. Vesicles are transported across neurons in our brains, spinal chords, and limbs. In all cases, the motion is generated by tiny protein machines, the molecular motors.
Work in my lab aims to understand how these protein machines convert chemical energy into mechanical work, by studying the motions and forces produced by purified motors and organelles. State-of-the-art optical trapping techniques are used to manipulate the motors, to apply force to them, and to measure the nanometer-scale motions they generate. A variety of tools from molecular biology and biochemistry are also used, to purify the proteins and organelles, and to modify the proteins in specific ways.
A current focus is to understand how motion and force are produced to separate the duplicated chromosomes before cell division. During mitosis, chromosome movements are linked to the depolymerization and growth of microtubule filaments. The ends of depolymerizing microtubules transmit tension to a specialized site on each chromosome, the kinetochore. Research on living cells has begun to reveal enough detail to reconstitute key aspects of kinetochore function using purified components. For example, isolated chromosomes and microspheres coated with motor proteins are pulled by the ends of depolymerizing microtubules in vitro. Adapting these assays for optical trapping will allow quantitative biophysical measurements that are not possible in living cells, and will provide new methods for testing models of kinetochore function.