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Reducing the Impact of Infectious Diseases by Supporting Trans-Disciplinary Academic Research

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Mark Yeager

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Mark Yeager is the Andrew P. Somlyo Distinguished Professor and Chair of Molecular Physiology and Biological Physics. His research focuses on assembly mechanisms of pathogenic viruses. By the use of electron cryomicroscopy (cryoEM), X-ray crystallography and molecular modeling, Mark Yeager and his colleagues have discovered key design principles for the assembly of major viral pathogens such as HIV-1, hepatitis B, hepatitis C, SARS and rotavirus. The application of “hybrid structural methods” is especially powerful for the examination of megadalton assemblies that are pleomorphic, as exemplified by his studies on HIV capsid assembly. Electron crystallography of engineered two-dimensional crystals of the HIV-1 capsid protein CA yielded the first subnanometer resolution map that showed the molecular design of the hexagonal lattice of the conical capsid. In addition, the cryoEM-based model enabled the engineering of disulfide bonds that stabilized the hexameric and pentameric CA building blocks of the capsid, so that high-resolution structures could be determined by X-ray crystallography. These results enabled the building of the first atomic model of the conical capsid that revealed the molecular basis for the continuously variable hexagonal lattice in the pleomorphic, conical capsid. Follow-on studies identified an interface in the lattice as a potential drug target and showed that the restriction factor TRIM5 assembled as a hexagonal lattice, which was templated by the CA lattice. Dr. Yeager has also investigated structures associated with pathogenesis of Neisseria, Pseudomonas, and cholera bacteria.

Ozlem Yildiz

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Ozlem Yildiz is an Assistant Professor of Business Administration at the University of Virginia Darden School of Business. Dr. Yildiz’s research studies the economics of and process improvements in service systems with a particular focus on applications in healthcare systems. In particular, her research concentrates on alleviating the congestion in service systems such as hospital Emergency Departments through designing payment schemes and process improvements. She has worked closely with the Emergency Department and Transporter System of the University of Rochester Strong Memorial Hospital. Dr. Yildiz’s research employs the methods of queueing theory,

game theory, simulation and data analysis.