Linda Nicholson

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 (picoseconds to nanoseconds, microseconds to milliseconds, 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 proline isomerization switches involved in Alzheimer`s disease and asthma, and in a fundamental coupling between innate immunity signaling and regulation of the actin cytoskeleton.