The major focus of my research is the investigation of relationships between protein dynamics and function, including function in the context of the cell and/or organism. We use NMR spectroscopy as our primary research tool to measure internal motions of individual bonds within a protein. NMR is a powerful tool for extracting amplitudes and time scales of motion with atomic resolution, and is able to detect motions over a wide range of time scales (ps – ns, micro – ms, and seconds to hours). From our studies thus far, we have learned that a ligand binding event is communicated from the protein – ligand interface to remote regions of the protein, and that the entire protein structure can contribute significantly to the binding energetics. Our studies have focused on proteins involved in disease processes (e.g. the proto – oncoprotein Src, the Lyme’s disease protein OspA, the amyloid precursor protein cytoplasmic tail APP-C), and have provided information to the scientific community that will assist in the development of novel therapeutic strategies. Our current objectives are focused on expanding our dynamics studies into thermodynamics and kinetics studies in order to obtain a more complete picture of the energy landscape of proteins. We are currently studying a key molecular switch involved in Alzheimer`s disease, in collabration with Kun Ping Lu at BIDMC, Harvard Medical School. As part of this work, we are investigating functional motions within the prolyl cis/trans isomerase enzyme Pin1 and their role in the amyloidogenic processing of the amyloid precursor protein. We are also studying the folding/unfolding reaction of the plant pathogen protein AvrPto, and aim to define thermodynamic stability parameters required for chaperone – independent secretion of the pathogen protein through the type III secretion system (TTSS) into the host plant cell. The TTSS is conserved from plants to humans, and our results should have high impact on our understanding of the requirements for secretion via the TTSS. Finally, we are completing our studies of the thermodynamics of the extended binding interface between the N- and C – terminal domains of ERM proteins, which serve as adapter molecules linking the plasma membrane to f-actin filaments. This binding is tightly regulated, and our studies should reveal details of how ERM proteins are activated by phosphorylation and by binding to cellular regulatory factors such as PIP2.