Core C: Structure, Computational, Protein Engineering

SUMMARY Flaviviruses and alphaviruses are enveloped, single-stranded RNA viruses that cause epidemics of human disease on a global scale, with new virus members regularly emerging and causing severe disease. The major goal of our Flavivirus and Alphavirus ReVAMPP (FLARE) Center is to establish ‘plug-and-play’ modular and optimized design technologies for vaccines and antibody

therapeutics against prototype flaviviruses and alphaviruses that can be readily applied to newly emerging related virus threats with pandemic potential. Research in our Structure, Computational and Protein Engineering Core C (hereafter Core C) will use structural biology, biophysics, molecular evolution, and computational biology to support the Projects and Cores of

this consortium. The ability to probe structures at a molecular level provides insight into the specificity and affinity of antigen-antibody interactions and guides iterative redesign of the antigen in collaboration with the Projects and Cores. Thus, using X-ray crystallography and cryo-electron microscopy (cryo-EM), structures of antibody-antigen complexes will be determined and

characterized (Kuhn/Fremont). Core C will provide the expertise required to engineer antibody and nanoparticle reagents that will be used to elicit and evaluate the immune response against target immunogens (Faissol/King). Molecular evolution analysis will be used to assess how envelope protein mutations can evade and shape the immune response (Bloom). Core C will

work closely with each Project and other Core research teams to ensure exchange of data and analyses to guide the efficient scientific development of consortium goals.