We apply physical techniques to study biological interactions. Currently our primary approach is optical tweezers where we apply a variety of techniques, including tethered particle motion, flow-forces, magnetic tweezers, and single-molecule fluorescence. We are now building a novel STED microscope to be used in the near future to study biological systems such as the ubiquitin-proteasome system in S. cerevisiae. Despite focusing heavily on instrumentation, our primary goal is to measure and understand underlying biological mechanisms.