A Lucille P. Markey Award was granted in 1987 to enhance structural studies of biological macromolecules at Purdue University. It provided $6.5 million over five years, subsequently extended with a $500,000 supplement, for hiring four new faculty; upgrading laboratory facilities; hiring of laboratory support staff, postdoctoral fellows, and graduate students; and funds for service contracts. Support for the shared facilities, extended and established with the Markey Award and later a Keck Foundation Award, were subsquently partly supported by the core component of two consecutive NIH AI Program Project Grants (PPG). In July 2003, we were awarded another major PPG in response to the NIH call for biodefense research, which provides for considerable improvement and extension of our virology facilities. However, it does not support the investigation of non-icosahedral, ssRNA, enveloped viruses nor the continuation of certain specific projects related to our earlier investigations of the icosahedral, ssRNA, enveloped alpha- and flaviviruses. Therefore, Richard Kuhn and Michael Rossmann are now seeking a smaller, third competitive renewal of the earlier PPG to support both our new direction into the structure of non-icosahedral viruses and to continue our previous studies. The core component is for partial support of the shared tissue culture, electron microscopy, and computing facilities. These facilities are shared with other current members of the Purdue Structural Biology Group who contribute proportionally to maintain these services. Three-dimensional structural and functional investigations will examine early (recognition, attachment, fusion, uncoating) and late (assembly and exit from the host cell) stages of viral infection and transmission. While previous studies have concentrated on icosahedrally symmetric viruses, we plan to slowly extend our technology to non-symmetrical, pleomorphic, ssRNA, animal and human viruses. The principal tools will be electron microscopy (Michael Rossmann, supported by Tim Baker), molecular biology and virology (Richard Kuhn), and X-ray crystallography (Michael Rossmann). Emphasis will be placed on """"""""higher"""""""" resolution structural studies of component proteins in combination with """"""""lower"""""""" resolution studies of the mature virus of assembly intermediates. The viruses to be studied are alphaviruses (especially Sindbis virus), flaviviruses (especially dengue virus, but also yellow fever virus and West Nile virus), coronaviruses (turkey and severe acute respiratory syndrome virus), bunyaviruses (especially Hantaan virus), and measles virus.
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