Biology with X-ray Lasers Biology with X-ray Lasers This proposal forms part of a multi-institution Science and Technology Center (STC) proposal to . If funded, the program would run for five years (renewable for another five) with twenty-five million dollar total budget (for 5 years) shared between SUNY (lead institution), Stanford, Milwaukee, UCSF, Cornell and ASU. About half the budget is devoted to outreach, technology transfer and education, run by centers at UC Davis and SUNY Buffalo. The research topic concerns the use of the recently-invented X-ray laser for structural biology. Our aim is to use the X-ray laser at SLAC, near Stanford, to obtain movies of molecular machines at work. The director of the STC is Prof E. Lattman at the Hauptman-Woodward institute at SUNY, the Director of Research is Professor Spence at ASU. A pre-proposal submitted in mid 2011 was successful. If funded, funding would start early in 2013. ASU faculty include: Fromme, Doak, Weierstall, Spence and Hogue (Biodesign). The development of hard x-ray, free-electron lasers (XFEL), as exemplified by the linac coherent light source (LCLS) at Stanford, promises a profound revolution in scientific knowledge. Synchrotron x-ray sources have transformed many areas of science over the past 40 years, including crystallography, materials science, high-pressure studies, and x-ray scattering, through their high brilliance, tunability, and pulsed beam structure. The LCLS is a technological leap over synchrotron sources producing X-ray pulses as short as 10 femtoseconds (10-14 seconds) containing up to 1013 photons. This pushes the experimental limit to smaller samples, weaker scatterers and finer time resolution. The beam produces coherent scattering across micrometer-sized objects, enabling whole new imaging modalities previously impossible. The LCLS, and counterparts under construction or planned, provide access to hitherto inaccessible experimental regimes. The STC on X-ray Lasers in Biology will focus its scientific efforts on the use of the FEL to determine structures, and to reveal dynamical behavior through snapshot imaging, of large macromolecular complexes and viruses that cannot easily be studied by other methods. Perhaps they cannot be crystallized (the principal precursor for structural studies); perhaps their action depends on large molecular motions, or perhaps they display structural variability on which biological interactions depend. These structures are crucial to our fundamental understanding of the molecular mechanisms and machines responsible for the biological world around us. Biology with X-ray Lasers 1. Prof. J.C.H.Spence (Physics). Professor Spence's research will be focused in three areas: 1. Molecular dynamics simulations of time-dependent molecular processes in enzymes and light-sensitive proteins. (in collaboration with Prof O. Beckstein, ASU Physics). 2. Simulation, theory and experimental work at LCLS in the SPI program aimed at understanding the factors which limit resolution in single-particle experiments at LCLS. 3. Development of improved sample delivery devices for structural and time-resolved scattering experiments at LCLS. This will include devices for fast solution scattering and serial crystallography intended to operate with the new high-repetition rate X-ray lasers coming on-line after 2018. Supported by: Assistant Research Scientist and 2 Physics Graduate Students. 2. Prof. P. Fromme (School of Molecular Sciences; SMS). Professor Fromme's group. Professor Fromme's research will focus on time-resolved serial femtosecond crystallography as well as time resolved diffraction studies in solution and spectroscopy (X-ray spectroscopy and optical spectroscopy) with the goal to determine the structure and dynamics of biomolecules in action . Special focus will be given to the study of the light-driven reactions in Photosystem II. This work will include methods development ranging from protein preparation and biophysical characterization, nanocrystallization and sample delivery (the latter one in collaboration with the Weierstall/Spence/Kirian groups at ASU) to novel method developments to trigger reactions in crystals and solution as well as development of methods for combining X-Ray emission and absorption spectroscopy, as well as optical spectroscopy with diffractive imaging using XFELs. The work will also include work on new data evaluation methods using continuous diffraction and finitive crystals sizes (in collaboration with the Chapman/Kirian groups). Supported by: Postdoctoral Research Associate and 2 Graduate Students. 3. Prof. U. Weierstall (Physics). Professor Weierstalls group will focus on: 1. Development and improvement of sample delivery devices for serial crystallography, e.g. mixing injectors, high viscosity injectors and liquid injectors using e.g. a recently acquired 2 Photon high resolution 3D printer to print new types of nozzles which cannot be build by hand. 2. Training and support of BioXFEL members and collaborators on sample injection related matters during and before beamtimes. 3. Weierstalls technician will make nozzles for BioXFEL beamtimes and work with the 3D printers in the lab. 4. Dissemination of high viscosity injectors to synchrotrons and XFELs around the world. Supported by: 1 Graduate Student. 4. Prof. B. G. Hogue (SOLS). Professor Hogues research will focus on the following areas. 1. Experimental work directed at optimized preparation and delivery of high quality virus samples for continued development of the XFEL for single-particle studies, including virus dynamics, as part of the LCLS SPI. 2. Structure and dynamics, including time-resolved studies, of viroporins and other viral membrane proteins using nanocrystals (in collaboration with Profs. Wei Liu and P. Fromme, ASU SOMS). 3. Contributions to testing and improvement of virus sample delivery using new injectors that are under development (in collaboration with Prof. R. Kirian, ASU Physics and R. Sierra, SLAC). Supported by: Postdoctoral Research Associate. 5. Prof. R. Kirian (Physics). Professor Kirians group will be focused on the development of (1) basic algorithms for ab initio structure determination using coherently illuminated nanocrystals and solutions of non-crystalline bioparticles, (2) experimental technique development for time-resolved crystallography and wide-angle solution scattering in collaboration with e.g. P. Fromme (ASU) and M. Brown (U. of Arizona), (3) the development of various sample injection schemes such as (a) aerosolized non-crystalline samples (in conjunction with CFEL and the LCLS Single-Particle Initiative team), (b) high-throughput fabrication techniques for liquid-jet generation (using a recently acquired high-resolution 3D printer at ASU), (c) particle guiding techniques based on optical forces (in continued collaboration with CFEL and Australia National University), and (d) high-speed liquid jets suitable for future high-repetition-rate XFELs (e.g. electrospray jets in collaboration with Ray Sierra at SLAC). Supported by: 1 Graduate Student.
|Effective start/end date||8/1/13 → 9/30/22|
- NSF-OD: Office of Integrative Activities (OIA): $11,719,981.00
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