A National Science Foundation Science and Technology Center BioXFEL Center Overview An STC Biology with X-ray lasers
STCs Mission A National Science Foundation Science and Technology Center … innovative, potentially transformative, complex research and education projects that require large-scale, long-term awards. STCs conduct world-class research through partnerships among academic institutions, national laboratories, industrial organizations, and/or other public/private entities, and via international collaborations, as appropriate. They provide a means to undertake significant investigations at the interfaces of disciplines and/or fresh approaches within disciplines….. STCs investments support the NSF vision of advancing discovery, innovation and education beyond the frontiers of current knowledge, and empowering future generations in science and engineering.
Key Scientific Objectives A National Science Foundation Science and Technology Center 3D Pictures and (later) Molecular Movies of Protein Structures Providing Insight into Biological Processes and Leading to Therapeutic Targets • 2014 marks the 100 th anniversary of crystallography • It also coincides (roughly) with the emergence of free- electron x-ray lasers (XFELs) as paradigm-shifting technology to: - Determine molecular structures - Monitor dynamics - Enable time-resolved studies of functional trajectories
The X-ray Laser Source A National Science Foundation Science and Technology Center • Spatially coherent 10fs x-ray pulses containing > 10 12 photons, enough to yield observable diffraction from a crystal 10 unit cells on edge. • Repetition rate of 120 Hz, rising to 2700 Hz in the next generation. • Energies of 10kV - hard x-rays. • Beam diameter as small as 0.1µm. • Provides stunning set of opportunities.
LCLS A National Science Foundation Science and Technology Center
Science Opportunities A National Science Foundation Science and Technology Center • Crystallography – Nanocrystals (NX) – smaller by 1000X than those used today; grow much more readily – Diffraction occurs before radiation damage takes effect – Non-frozen specimens – µs diffusion into NX allows new classes of time- resolved experiments
Science Opportunities II A National Science Foundation Science and Technology Center • Solution scattering – Pulses freeze motions; no time averaging; time- resolved studies – Small numbers of particles can produce an observable 2D pattern that contains much more information than usual circularly symmetric one – Insightful math and algorithms may lead to recovery of diffraction pattern of a single molecule, thus to a structure – More signal than single particle scattering
Science Opportunities III A National Science Foundation Science and Technology Center • Single particle imaging – Ultimate nanocrystal: no crystallization problem – Full dynamic spectrum unfettered by lattice – Wet specimen at room temperature – Molecular movies – Experimentally most challenging
The three kinds of BioXFEL snap-shot diffraction experiments A National Science Foundation Science and Technology Center Note dimensions in microns. X-ray beam Many particles per shot Fast WAXS X-ray beam Single particle per shot. Many X-ray shots do not X-ray beam hit a crystal Single nanocrystal per shot. 9
Scientific and Technical A National Science Foundation Science and Technology Center Challenges • Almost nothing from standard experiments carries over to the XFEL. In SFX for example: – Tiny crystals have to be delivered one at a time to coincide with the x-ray pulses – Diffraction patterns: one shot per crystal • All spots are partials • Fringes and other unfamiliar features • Difficult solvent effects • Pulse-to-pulse variation in intensity
Scientific and Technical A National Science Foundation Science and Technology Center Challenges - II • In SAXS a single fs-scale pulse illuminates a volume containing a small number of molecules, producing a diffraction pattern that has azimuthal as well as radial variation. – BioXFEL groups seek to recover the Fourier transform of individual molecules from these data; such transform can be phased to recover a molecular structure. – These molecules undergo structural fluctuations.
Scientific and Technical A National Science Foundation Science and Technology Center Challenges - III • In SPI for example: – Scattering from single particle very weak – higher resolutions are far off. – Particle to particle variation requires smart binning to capture similar subfamilies. – Particles scatter in random orientations: correlating these will be very difficult. – Got to hit the beam…
Key Center Objectives A National Science Foundation Science and Technology Center • Nucleate a diverse community of scholars, students, and interested laypersons that will support and develop the transformative capacities of XFELs. • Make our research results and our technology achievements widely available to all appropriate groups. • Develop a broad range of collaborations world-wide.
BioXFEL Organizational Structure A National Science Foundation Science and Technology Center
Graduate Students A National Science Foundation Science and Technology Center • Grad students gain primary training in program at home institution. We need to enrich and unite. – Courses on BioXFEL topics – Center-wide professional development – GS get to be mentors as well as to be mentored – On-line journal club recorded for replay – Annual meeting
Science and Technology Center Beamtime Proposal Reviews A National Science Foundation • Insightful John has instituted collective reviews of STC beamtime proposals for each cycle at LCLS. – Merging proposals makes them better and improves chances of time being awarded. – The exchange of proposals is a powerful internal communication channel for BioXFEL. – Builds community.
Steering Committee A National Science Foundation Science and Technology Center Name Role Scientific Thrust Area Eaton Lattman Center Director John Spence CoPI, Scientific Director Sample delivery, SFX methods, analysis, theory Petra Fromme CoPI Structures and mechanisms in photosynthesis Abbas Ourmazd CoPI Single-particle Theory Edward Snell Participant Crystallization, SAXS George Phillips Participant Heterogeneity, dynamics Alexander Cartwright VPR UB Margarita Dubocovich Education Director Kenneth Tramposch Knowledge Transfer Thomas Furlani Computation Director Jill Szczesek Managing Director
Steering Committee A National Science Foundation Science and Technology Center • Committed to consensus management. • Model of separate Center and Scientific Directors proving effective. • All major issues discussed by the SC, usually by teleconference. • Example: the saga of the budget cut that tested the SC model, but never came to pass.
Software A National Science Foundation Science and Technology Center • Livermore Software conference – Organized as a collaboration between the Physical Biosciences Division of LBNL, and BioXFEL. – A multi-day school & workshop with entire range of developers. Seminars on the latest XFEL methods; opportunity for students to process real or example data with various programs. – Course materials will be archived on the Web. – Another example of community.
How are we doing? A National Science Foundation Science and Technology Center • STC less than nine months old at time of review. • Lots of good press - see https://www.bioxfel.org/news. • Before official award approximately 25 papers involving one or more BioXFEL STC co-authors. • Since the award there are at least 23 published papers with four in press that are supported by and acknowledge the BioXFEL STC. Many of these are in high profile journals.
How are we doing? A National Science Foundation Science and Technology Center • 4-day Royal Society meeting on XFELs held in October 2013 was co-organized by John Spence. • Conference proceedings on line June 9, 2014 in a special issue of Philosophical Transaction: 27 papers. • 11 are co-authored by STC-supported investigators, and an additional three are co- authored by close collaborators. • This issue will be a central document in XFEL science for years to come.
How are we doing? A National Science Foundation Science and Technology Center • BioXFEL technology critical to the field – Weierstall’s lipid cubic phase “toothpaste jet” vehicle for the delivery of membrane protein crystals to the XFEL beam. – This protein-sparing device ➞ crystallography of many membrane proteins for which protein production has been a fatal bottleneck. – ASU is devoting major resources into providing LCP delivery systems to other institutions, and it providing tutorials so that others can make them independently. – Work is even beginning on fabricating them by high- resolution 3D printing. Parallel studies are already under way to develop high-viscosity, water-based jets for the study of crystals of soluble proteins.
Recommend
More recommend
