Capturing Snapshots of the Cell Invasion Machinery of Influenza Virus and HIV
Prof. Kelly Lee
Medicinal Chemistry, University of Washington
February 13, 2014
Foege N130A, Wallace H. Coulter Seminar Room
We seek to understand the mechanics of protein-mediated membrane fusion, which lies at the heart of host cell invasion by enveloped viruses as well as fundamental cellular processes such as synaptic signaling, vesicle trafficking, gamete fertilization, and cell–cell fusion. Using complementary biophysical approaches including cryo-electron tomography, small-angle X-ray scattering, and hydrogen/deuterium-exchange mass spectrometry– techniques suited to analyze these highly dynamic processes under native conditions– we have begun to dissect the structural reorganizations that take place as viral fusion proteins become activated, grapple to membranes, remodel and deform the membranes, and induce them to merge together. Our studies of membrane fusion and fusion proteins in influenza virus and HIV may also lead to elucidation of targets for fusion inhibitor agents, a better understand of antibody neutralization, and identification of structural factors key to rational vaccine immunogen design.
Dr. Lee received his A.B. in Physics from Harvard University and his Ph.D. in Biophysics from the Johns Hopkins University. As a postdoctoral fellow in Jack Johnson’s group at the Scripps Research Institute, he studied mechanisms of conformational change in viruses. An NIH K99/R00 award enabled him to pursue investigation of influenza virus’s membrane fusion process using cryo-electron microscopy and other biophysical techniques. His research in the Department of Medicinal Chemistry focuses on the structure and dynamics of membrane fusion proteins in influenza and HIV, with the goals of understanding how the specialized glycoprotein machinery mediates membrane remodeling during cell invasion and determining how it interacts with cellular receptors and antibodies.