Biomolecular imaging at LCLS
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The Linac Coherent Light Source (LCLS) is a brand new Department of Energy (DoE) user facility located in the San Francisco Bay Area. Scheduled to come online in 2009 this first-of-a-kind X-ray source will be the world’s first 4th generation X-ray source in the hard X-ray regime and offers ultra-short (~100 femtosecond) X-ray pulses of unprecedented brightness (~10^12 photons/pulse). The revolutionary capabilities of this new X-ray source are anticipated to generate a wealth of ground-breaking new science. Amongst many applications in ultrafast science, LCLS offers the potential to revolutionize structural biology by enabling atomic resolution imaging of virtually any macromolecule, protein complex, or virus. The technique that will enable this is single-particle diffraction. By using ultra short and intense X-ray pulses, a diffraction pattern could be recorded from a particle such as a single molecule. The molecule will subsequently explode, but if the timescale for structural change (at the Angstrom scale) is longer than the pulse duration, then the diffraction pattern will represent the undamaged molecule. By removing the need to crystallize a protein or protein complex, large classes of structures could be determined that would be otherwise intractable. This capability will ultimately enable the rapid detection of biological agents and the development of new medical diagnostics and therapeutics. LLNL has been leading a highly-successful effort to realize ultrafast single molecule imaging at LCLS. The high profile of XFEL science is evidenced by the number of publications that it has generated, many in high impact journals such as Physical Review Letters and Nature Physics. So far the LLNL group has published or had accepted over 15 peer-reviewed papers, two featured on covered. The effect of these can be quantified in the number of invitations we have received to talk at conferences: over 12 in the last 6 months. It would be highly beneficial for both LLNL and UC to promote and develop synergistic links with researchers at UC campuses in this rapidly moving field. We seek to use the UC fee grant to develop this linkage between UC campus research and LLNL. Specifically, we request resources to fund a portion of LLNL researcher time to mentor two UC students, postdoctoral fellows and/or research specialists, and associated support costs involved supporting their work and for travel to experiments. . Knowledge will be transferred cross-institutionally by a vigorous program of collaboration and staff exchanges between LLNL and UCD, to enable close interaction between LLNL staff with UCD students. Our goal is to perform a set of integrated groundbreaking experiments at LCLS as soon as that facility comes online to test the key concepts of single-molecule XFEL imaging, develop key technologies, and to tackle the formidable data processing challenges using the Laboratory’s high-performance computers such as Thunder. We aim to use this project to nucleate a cross-disciplinary, multi-institution Centre for Coherent X-ray Imaging spanning multiple UC campuses and National Laboratories to pursue novel imaging techniques with application to both biological and material science problems. The long-term vision is to leverage this 3-year collaborative project to nucleate a new NSF centre in ultrafast X-ray imaging, generating transformational technologies based around applications of new X-ray sources such as LCLS to both biological and materials science problems. Additional funding streams from NIH, NSF and private foundations will also be pursued as part of our exit strategy. The outcome will be a high-profile program in XFEL science spanning both LLNL and UC campuses, and is anticipated to result in a significant number of high-profile publications in the highest quality journals.