SLAC National Accelerator Laboratory

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  • Soichi Wakatsuki

    Soichi Wakatsuki

    Professor of Photon Science and of Structural Biology

    Current Research and Scholarly InterestsUbiquitin signaling: structure, function, and therapeutics
    Ubiquitin is a small protein modifier that is ubiquitously produced in the cells and takes part in the regulation of a wide range of cellular activities such as gene transcription and protein turnover. The key to the diversity of the ubiquitin roles in cells is that it is capable of interacting with other cellular proteins either as a single molecule or as different types of chains. Ubiquitin chains are produced through polymerization of ubiquitin molecules via any of their seven internal lysine residues or the N-terminal methionine residue. Covalent interaction of ubiquitin with other proteins is known as ubiquitination which is carried out through an enzymatic cascade composed of the ubiquitin-activating (E1), ubiquitin-conjugating (E2), and ubiquitin ligase (E3) enzymes. The ubiquitin signals are decoded by the ubiquitin-binding domains (UBDs). These domains often specifically recognize and non-covalently bind to the different ubiquitin species, resulting in distinct signaling outcomes.
    We apply a combination of the structural (including protein crystallography, small angle x-ray scattering, cryo-electron microscopy (Cryo-EM) etc.), biocomputational and biochemical techniques to study the ubiquitylation and deubiquitination processes, and recognition of the ubiquitin chains by the proteins harboring ubiquitin-binding domains. Current research interests including SARS-COV2 proteases and their interactions with polyubiquitin chains and ubiquitin pathways in host cell responses, with an ultimate goal of providing strategies for effective therapeutics with reduced levels of side effects.

    Protein self-assembly processes and applications.
    The Surface layers (S-layers) are crystalline protein coats surrounding microbial cells. S-layer proteins (SLPs) regulate their extracellular, self-assembly by crystallizing when exposed to an environmental trigger. We have demonstrated that the Caulobacter crescentus SLP readily crystallizes into sheets both in vivo and in vitro via a calcium-triggered multistep assembly pathway. Observing crystallization using a time course of Cryo-EM imaging has revealed a crystalline intermediate wherein N-terminal nucleation domains exhibit motional dynamics with respect to rigid lattice-forming crystallization domains. Rate enhancement of protein crystallization by a discrete nucleation domain may enable engineering of kinetically controllable self-assembling 2D macromolecular nanomaterials. In particular, this is inspiring designing robust novel platform for nano-scale protein scaffolds for structure-based drug design and nano-bioreactor design for the carbon-cycling enzyme pathway enzymes. Current research focuses on development of nano-scaffolds for high throughput in vitro assays and structure determination of small and flexible proteins and their interaction partners using Cryo-EM, and applying them to cancer and anti-viral therapeutics.

    Multiscale imaging and technology developments.
    Multimodal, multiscale imaging modalities will be developed and integrated to understand how molecular level events of key enzymes and protein network are connected to cellular and multi-cellular functions through intra-cellular organization and interactions of the key machineries in the cell. Larger scale organization of these proteins will be studied by solution X-ray scattering and Cryo-EM. Their spatio-temporal arrangements in the cell organelles, membranes, and cytosol will be further studied by X-ray fluorescence imaging and correlated with cryoEM and super-resolution optical microscopy. We apply these multiscale integrative imaging approaches to biomedical, and environmental and bioenergy research questions with Stanford, DOE national labs, and other domestic and international collaborators.

  • Faya Wang

    Faya Wang

    Lead Scientist, SLAC National Accelerator Laboratory

    Bio• 20-year scientific career in academia and national lab
    • Pursuing research leadership position in high-impact cutting-edge tech organization
    • Extensive hands on experience on particle accelerator and rf system
    • Electron beam dynamics, beam optics, control system dynamics, accelerator design, electrodynamics, electromagnetic field, high power microwave system, beam and rf diagnostics, electromagnetic field design

  • Xijie Wang

    Xijie Wang

    Distinguished Scientist, SLAC National Accelerator Laboratory

    BioXijie Wang is a distinguished scientist and the founding director of SLAC MeV-UED user facility at SLAC National Accelerator Laboratory. Xijie Wang has more than 30 years' experience in accelerator physics, free electron laser, THz, and ultrafast science and technology. Xijie pioneered the idea using mega-electron-volt electrons for ultrafast electron diffraction (MeV-UED) and ultrafast electron microscope (MeV-UEM). Under Wang’s direction, SLAC has become the world leader in ultrafast electron scattering technologies including single-shot, diffuse scattering, micro-diffraction, operando and in-situ, the first ever femto-second gas and liquid phase UED. These technologies have opened new frontiers in ultrafast science and materials in extreme conditions, produced insight into ultrafast structure dynamics of 2-D materials; control of the topological properties of matter; and atomic & molecular movies of complex materials such as perovskite and fundamental chemical processes in gas and liquid phases. He established the first ultrafast electron scattering user facility in the world – SLAC MeV-UED in 2019. Xijie Wang initiated superconducting RF gun R&D program at SLAC, and he led the effort established SRF gun R&D for LCLSII-HE.

    Prior to his time at SLAC, Wang spent over 20 years at Brookhaven National Laboratory (BNL), where he led development and operations of the Accelerator Test Facility (ATF) and the Source Development Laboratory (SDL). Wang played a leading role in research on laser accelerators, high-brightness electron beams, X-ray free electron lasers (FEL), RF deflector for LCLS, THz and MeV-UED at BNL. He developed photocathode RF gun injectors that derived the first saturation of both high-gain harmonic generation (HGHG) FEL at BNL’s ATF and Self-amplified spontaneous emission (SASE) FEL at Argonne National Laboratory. Wang and his collaborators carried out a series of pioneering FEL experiments in early 2000s: 2nd to 4th harmonic HGHG, VISA (Visible to Infrared SASE Amplifier) SASE FEL and nonlinear harmonic generation characterization; super radiance FEL, detuning and tapering for FEL efficiency improvement.

    Xijie Wang has co-authored over 300 publications, including 8 in Science, 3 in Nature, 6 in Science Advances, 14 in Nature family journals, and over 20 in PRL.