Biology with X-ray Lasers
Eaton Lattman Principal Investigator
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Intellectual Merit<br/><br/>Vision: The Stanford Linac Coherent Light Source (LCLS) provides hard laser x-ray pulses as short as 10 fs, capable of probing nano-samples on biological reaction time scales. The Center for Biology with X-ray Lasers (BioXFEL) will use the LCLS's laser x-ray source to attack recalcitrant structural biology problems and apply the gained knowledge and expertise to the development of tools and techniques that will be widely applicable in structural biology. The x-ray free electron laser (XFEL) at the LCLS brings at least four new modalities to the fore. (1) Many macromolecules that appear not to crystallize actually form nanocrystals (as small as 10 nm on edge), and the ability to study nanocrystals is possible with XFELs. (2) The short XFEL pulse length allows observation of macromolecular dynamics. (3) XFELs dramatically increase the information yield from x-ray solution scattering. (4) As beam technology develops, studies of single particles - the ultimate nanocrystal - will become possible. <br/><br/>Research plan: XFEL-based imaging brings an unprecedented combination of spatial and temporal resolution to bear on biological samples. BioXFEL will develop every aspect of this imaging work: growth of nanocrystals; specimen delivery into a tiny XFEL beam; data processing and phasing algorithms; molecular movies and more. In each case, the difficulty varies. Conventional crystallography of larger crystals provides a firm platform for nanocrystal work. At the other extreme, non-crystalline, single-particle studies will require creative developments to achieve successful imaging. The integrative approach of the Science and Technology Center (STC) will be critical to meeting these and other challenges. Within BioXFEL each experiment will also be a test of hardware and software that will provide a platform for improvement.<br/><br/>Scientific legacy: BioXFEL expects to leave the scientific community with: (a) Hardware and software innovations and developments that will enable facile implementation of an array of XFEL structural biology experiments spanning a broad range of specimen types and dynamic regimes. (b) A portfolio of successful structural projects that provide key insights and illustrate the capacities of the XFEL. (c) A diverse community of talented scholars in the US and internationally, with deep interest in and commitment to XFEL science, who will nucleate and promote new projects. (d) Broadened public awareness of XFEL science in particular and of biological imaging in general.<br/><br/>Broader Impacts<br/><br/>Important constituencies: BioXFEL will implement a far-ranging, integrated plan to create constituencies that benefit from the efforts of the STC and contribute to it. The principal constituencies are: students and trainees; a community of scholars that will nucleate around XFEL science and technology development; a larger scientific community that is aware of the capabilities and importance of XFELs; and the public at large. <br/><br/>Education: BioXFEL spans seven academic campuses. Distributive education and professional development training will be accomplished in the CLIMB program (designed to promote advanced skills for interdisciplinary research) through multiple means, including inter-campus on-line course modules for aspects of XFEL science. An integrated web of training and personal interactions will build the current and future BioXFEL community. Linked to this is the "Scientific Villages", project-driven educational outreach courses associated with XFEL science, which is being created at Arizona State University. <br/><br/>Diversity will be integrated into the fabric of BioXFEL's human resources and education programs. The CLIMB program which enrolls approximately 60% underrepresented minority students, recruits students to its broad range of enrichment programs from a variety of sources including McNair Scholars and visits to a variety of undergraduate-oriented events such as SACNAS. This program will be expanded to cover all campuses participating in BioXFEL.<br/><br/>Knowledge transfer is a key component of a distributed center. BioXFEL will communicate with users and potential users through: (1) distribution of software, representative data sets and related information, through a computing resource at The University at Buffalo; (2) indexing in Science Citation Index databases of protocols and other important information that are now often hidden in silos; (3) short-term visits to BioXFEL campuses and other facilities to train colleagues in the use of specimen delivery systems, or for purposes of collaboration; (4) a comprehensive web presence.