Intellectual Merit: The long-term goal of this project is to determine the three-dimensional structure of viruses at atomic resolution. An accurate knowledge of viral structure is necessary to understand the mechanism of infection at the molecular level. Many viruses cannot be crystallized for structure analysis by standard crystallographic methods. Using the high intensity X-ray radiation pulses generated at the X-ray free electron laser facility LCLS in Stanford, diffraction patterns from single virions can be obtained. Due to the short X-ray pulse duration of 10-100 fsec, each virus particle generates a diffraction pattern before radiation damage destroys the particle. The virus particles will be injected into the X-ray beam via two methods: 1. An electrospray or nebulizer aerosol injector with aerodynamic particle focusing, which has been developed at LLNL. 2. An aerojet source developed at ASU, which provides a monodirectional beam of droplets containing the viruses. The electrospray source delivers dehydrated particles at low particle density, whereas the aerojet source delivers fully hydrated samples with high particle density to the X-ray beam. After each X-ray pulse a single particle diffraction pattern is read out. These patterns from many particle orientations will be classified, sorted, merged and phased to form a three-dimensional electron charge density map of the virus.
Broader Impact: The work will be made available in simplified form to the existing "Science is fun" program at ASU, administered through the LeRoy Eyring Center for Solid State Physics at ASU. In addition, the material will be presented at the Central Arizona Science and Engineering Fair.
The results of the project will form the basis for a new generation of instrumentation that may rapidly solve virus structures, which are difficult to crystallize. This interdisciplinary research will bring together elements of biochemistry, molecular biology, fluid dynamics, coherent X-ray imaging, classification and phasing algorithm development and in doing so will promote research and learning in integrated science areas that will greatly benefit its participating students and postdoctoral associates. The results of this research will be disseminated in the form of peer reviewed papers and posters/talks at conferences.
