Structural Molecular Biology
Overview
The goal of understanding biological structure and function, and applying this knowledge to address a wide range of problems of broad societal importance has evolved into a large, worldwide multidisciplinary effort. It engages academic, national laboratory and corporate researchers whose goals range from innovative, discovery-based science through applied uses like more effective approaches to bioremediation and the acceleration of drug discovery. Knowledge in this field has relevance to solving grand challenge problems related to medicine, energy, and the environment. The SMB program has pioneered and will continue to lead development of new and enhanced approaches for the investigation of biomolecular structure and function, making them widely and rapidly available to the biomedical, bioenergy, biogeochemistry, and environmental research communities.
Structural biology is a field focused on understanding biological macromolecules such as proteins and RNAs.
The focus of the SMB program is on an integration of macromolecular X-ray crystallography (MC), biological small angle X-ray scattering/diffraction (SAXS), X-ray imaging, and X-ray absorption (XAS) and emission spectroscopy (XES) to study the most challenging and wide-ranging biological systems – leveraging on the powerful capabilities of the SSRL synchrotron (SPEAR3) and LCLS X-ray free electron laser. Collectively, these techniques provide a remarkably rich and broad window on structure and function across a range of biologically relevant length and time scales, providing the foundation to extend results at the atomic and molecular level to understanding complex macromolecular interactions, and to studies of organelle, cell and tissue organization and function.
The SMB program works closely with the SLAC Biosciences Division in emerging scientific areas related to bioenergy and biogeochemistry, where X-ray techniques provide unique tools for studies in the length scale ranges from molecular to cellular and beyond. The current strategic emphasis at SLAC on evolving a cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET) program, will provide a unique opportunity for joint scientific and technological developments, which will be vigorously pursued. The SMB program will form partnerships with Stanford University institutes, such as ChEM-H and Bio-X, expanding on existing joint programs for MC beam line development and science, with industry on drug discovery developments, and with private institutions on emerging scientific topics. The SMB program will engage with other user facilities, pursuing multi-user facility arrangements in areas that provide user access to complementary techniques, such as with the Environmental Molecular Science Laboratory (EMSL) and the Joint Genome Institute (JGI), and in coordinated outreach programs within BER-funded facilities and research groups. We also plan to begin targeted outreach to potential new SMB users at the BER Bioenergy Research Centers. The Joint Initiative for Metrology in Biology (JIMB) now resides administratively within SSRL, and we are pursuing synergistic lines of research connecting JIMB’s synthetic biology and genomics expertise with SMB research and capabilities at SSRL.
SMB Programs
![Chemistry & Catalysis](/ssrl/web/sites/default/files/images/smb-mc2_0.jpg)
Macromolecular Crystallography
Study biological molecules such as proteins, viruses and nucleic acids (RNA and DNA) to resolutions approaching 1 Å. This high resolution helps elucidate the detailed mechanism by which these macromolecules carry out their functions in living cells and organisms.
![SAXS](/ssrl/web/sites/default/files/images/smb-saxs_0.jpg)
Biological Small Angle X-ray Scattering/Diffraction
A powerful experimental technique used to probe the structure of biological materials (such as proteins, large protein complexes, viruses, lipids etc.) at length scales that bridges the gap between atomic resolution structures to molecular/subcellular levels.
![XAS](/ssrl/web/sites/default/files/images/smb-xas_0.jpg)
X-ray Absorption and Emission Spectroscopy
The SMB BioXAS program has developed one of the largest dedicated and most impactful activities in the world with optimized beam lines and specialized instrumentation and analysis capabilities for enabling biological, biomedical, and bioenergy research.
![Nobel](/ssrl/web/sites/default/files/images/nobel-prizes.jpg)
Nobel Prizes
The 2006 Noble Prize in Chemistry was awarded to Roger Kornberg for research carried out in part at SSRL. Kornberg revealed the process of transcription, through which DNA's genetic blueprint directs the manufacture of proteins.
Partnerships & Collaborations
![Cryo-EM Cryo-EM](/ssrl/web/sites/default/files/images/smb-cryoem.jpg)
Cryo-EM (Cryogenic Electron Microscopy) Facility
Cryo-EM generates 3-D images at nearly atomic resolution of viruses, molecules and complex biological machines inside the cell, such as the ribosomes where proteins are synthesized. By flash-freezing these tiny things in their natural environments, scientists can see how they are built and what they do in much more detail than before, stringing thousands of images together to create stop-action movies and even taking virtual “slices” through cells, much like miniature CT scans.
SLAC Biosciences Division
The Biosciences Division builds on SLAC’s unique strengths in X-ray based research to explore biological function on multiple scales, from individual genes, proteins and enzymes to molecular ecosystems. SLAC’s world-class capabilities in ultrafast and high-throughput macromolecular crystallography, small-angle x-ray scattering, imaging and spectroscopy are optimal for revealing the physical and electronic structures of macromolecules in particular – the cornerstones of biological systems.
![SLAC Biosciences Division SLAC Biosciences Division](/ssrl/web/sites/default/files/images/smb-slacBio.jpg)
![MFX MFX](/ssrl/web/sites/default/files/images/mfx_overview.jpg)
Multi-User Facility Collaborations
Contacts & Resources
Future Capabilities
SMB Area | Diffraction | Scattering | Spectroscopy & Imaging | ||
---|---|---|---|---|---|
Macromolecular Crystallography | Micro-Beam, Undulator for Micro- to Nano-Crystallography | Micro- to Nano-Crystallography Instrumentation at LCLS | |||
Biological SAXS | Microfocus Optics; High-Speed Detector | ||||
Biological XAS and XES | New Detector Approaches | Advanced Spectroscopy Undulator (XES, XRS, RIXS, HERFD/XAS) | |||
Picosecond to Femtosecond Time Domain | Micro- to Nano-Crystallography Instrumentation at LCLS | Advanced Spectroscopy Undulator (XES, XRS, RIXS) and LCLS |
Publications
Curated list goes here
Science Highlights
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Training Scientists of the Future
One of the goals of the Macromolecular Crystallography (MC) group is to actively train and educate the next generation of scientists through Workshops, Summer Schools, Conference Lectures, Internship Programs and one-on-one mentoring at the beamline stations. Training typically consists of lectures, hands-on experiments, data analysis and interpretation of results. Novice and experienced users are trained in the optimal use of the X-ray beamlines, particularly when new instrumentation and/or new emerging methodologies are first implemented. Each year, the MC group hosts multiple local and remote workshops, provides more than 30 conference lectures, and mentors a large group of summer interns.
Lecture Series
The Macromolecular Crystallography group members present lectures and scientific talks at local, national and internaltional meetings, conferences, summer schools and workshops - about 30 each year - providing information about experimental techniques, the beamline stations, new instrumentation and new methodology implementations.
Conferences and Summer Schools
MC group members provide a large number of scientific lectures at conferences and in school settings, covering a host of topics that have included X-ray diffraction techniques, robotic sample handling, remote access, automated piplelines and structural studies. Conferences include the Annual SSRL/LCLS Users' Meeting, the Triannual West Coast Protein Crystallography Meeting, the Annual American Crystallography Association Conference, and the Biannual Synchrotron Radiation Instrumentation Meeting. School lectures include the Annual RapiData Workshop, the annual Cold Springs Harbor Crystallography Course, the SSRL Structural Molecular Biology Summer School and the Stanford Synchrotron Summer School.
Public Lectures
MC group members provide scientific lectures tailored for the general public. These lectures are a part of the SLAC Public Lecture Series and are held periodically on the SLAC campus.
Summer Internships
Full list of internship programs
Each year the Structural Molecular Biology (SMB) group participates in several DOE summer internship programs at SLAC, accepting interns with interests in biology, biochemistry, biophysics, engineering, robotics and software development. Students are paired with staff members and are given specific projects to work on for the duration of the internship. Students also attend scientific lectures and participate in a number of events to help them prepare for a career in science. The SMB group particularly encourages applications from students belonging to groups under-represented in science, such as women, minority students and low-income students.
Workshops & Summer Schools
The Macromolecular Crystallography group members mentor, educate and actively train about 150 researchers each year through remote workshops, basic data collection and processing workshops and specialty workshops with lectures and hands-on training when new beamline instrumentation or other new methodologies become available.
Remote Access Workshops
A number of workshops are held each year in remote locations to train scientists in the use of the SSRL beamline stations. Participants learn the practical aspects of crystal preparation and shipment to SSRL, remote data collection and data processing. Remote workshops have been held in New York, Alabama, Pennsylvania, Puerto Rico, Mexico and Australia.
RapiData Workshops
The RapiData workshop, held yearly, is an intense 6-day course concentrated on macromolecular x-ray crystallography data collection, data processing and structure solving methods and techniques. The aim of this workshop is to educate and train young scientists in data collection and data processing methods at synchrotron beam lines, using state-of-the-art software and instrumentation. Participants are encouraged to bring their own samples for data collection, as well as previously measured data for processing and structure solution.
Specialty Workshops
Specialty workshops are primarily designed to disseminate and train new users as well as experienced users in new methods and new beamline instrumentation when they first become available. Specialty workshops have included robotic sample mounting, nano-crystallization, single crystal UV-Vis spectroscopy and several other crystallography-related methods and complementary techniques.
Past Events
2020
2019
Time- and Space-Resolved X-ray Absorption Spectroscopy (XAS) at SSRL: Analysis of Large Data Sets
As SSRL transitions from step-scanning XAS to continuous scanning and quick scanning (QEXAFS), time resolution will improve from 10 minutes per spectrum to below 1 second, meaning that the number of spectra that will need to be analyzed will increase dramatically. A similar situation already exists with space-resolved data in X-ray microscopy where thousands and sometimes even millions of spectra need to be processed. With these new parameters, we need appropriate software to process these data batches and extract time- and space-resolved chemical information. This course will present examples of large XAS data sets and solutions for their batch processing, including hands-on exercises. The future in correlated data collection and analysis will also be discussed.
RapiData 2019 at SSRL
Synchrotron radiation is an indispensable tool in macromolecular crystallography and most of the macromolecule structures deposited in the PDB are solved and refined with data collected at synchrotron sources. Some of the skills needed to make optimal use of state-of-the-art beamlines and data processing and analysis software are difficult to learn without intensive hand-on training.
2019 Resonant Inelastic X-ray Scattering with Hard X-rays
This workshop on the fundamental aspects of hard X-ray Resonant Inelastic X-ray Scattering (RIXS) includes lectures and tutorials. Hard X-ray RIXS is a powerful spectroscopic tool due to the two-dimensional data planes, the high resolution in the energy transfer direction and the large penetration depth of the X-rays.
2018
Metals in Structural Biology
A workshop held at the joint SSRL/LCLS Users' Meeting September 25, 2018. This workshop showcased the SMB groups expertise in combining spectroscopic methods (EPR, UV-vis, and X-ray spectroscopy), with macromolecular crystallography.
EXAFS 2018 - SSRL Summer School on Synchrotron X-Ray Absorption Spectroscopy
SSRL conducted the 2018 SSRL Summer School on Synchrotron X-Ray Absorption Spectroscopy between August 13 and August 16. Due to high demand an extra session of the summer school was added and held between September 10 and September 13. The five-day sessions provided training in XAS and Imaging theory, experimental design, data acquisition strategies and FEFF based EXAFS data analysis useful to both new and experienced users.
EMSL Integration 2018
A tutorial and introductory workshop to the X-ray methods available to general users at the SSRL at SLAC, aimed at providing an overview on SMB methods and techniques was held during the EMSL Users Meeting on August 8, 2018. The tutorial was jointly organized by SSRL SMB and NSLS staff.
RapiData 2018 at SLAC - Data Collection and Structure Solving: A Practical Course in Macromolecular X-Ray Diffraction Measurement
RapiData at SLAC is a practical course in macromolecular X-ray diffraction data collection, data processing and structure solution. In addition to macromolecular crystallography the course also included lectures and tutorials on small angle X-ray scattering methods. The aim of the course, held from April 22-27, is to educate and train young scientists in data collection and processing methods at synchrotron beamlines, using state-of-the-art software and instrumentation.
University of Alabama at Huntsville Collaborative Remote Access Workshop
A workshop on the Remote Access Crystallography and the Small Angle X-ray Scattering programs at SSRL was taking place on March 8. The workshop included lectures, remote access crystallography training using the SSRL facilities and tutorials on fixed target and injector methods for serial crystallography at SSRL and LCLS.
2017
Small Angle X-ray Scattering in Structural Biology: A Hands-On Practical Workshop
This workshop focused on all aspects of the experimental application of state-of-the-art synchrotron-based solution X-ray scattering to biological macromolecules and macromolecular complexes. The workshop was split over four days (November 6, November 20-21 and December 4) included introductory lectures, hands-on data collection and data analysis tutorials.
Advanced X-ray Spectroscopy at SLAC: From Theory to Experimental Concepts
A workshop at the joint SSRL/LCLS Users' Meeting September 29, 2017. The emphasis of this workshop was to enable a wider understanding of the diversity of theoretical approaches available at SLAC and their relevance to cutting-edge experiments at SSRL and LCLS investigating electronic structure and dynamics in different application domains.
New Tools for Macromolecular Structure Determination at Physiological Temperatures
A workshop at the joint SSRL/LCLS Users' Meeting September 27, 2017. The workshop focused on new methods available at SSRL and LCLS for protein crystallography at room temperature.
EXAFS 2017 - SSRL Summer School on Synchrotron X-Ray Absorption Spectroscopy
SSRL conducted the 2017 SSRL Summer School on Synchrotron X-Ray Absorption Spectroscopy between June 19 and June 23. The five-day session provided training in XAS and Imaging theory, experimental design, data acquisition strategies and FEFF based EXAFS data analysis useful to both new and experienced users.
RapiData 2017 at SLAC - Data Collection and Structure Solving: A Practical Course in Macromolecular X-Ray Diffraction Measurement
RapiData at SLAC is a practical course in macromolecular X-ray diffraction data collection, data processing and structure solution. In addition to macromolecular crystallography the course also included lectures and tutorials on small angle X-ray scattering methods. The aim of the course, held from April 16-21, is to educate and train young scientists in data collection and processing methods at synchrotron beamlines, using state-of-the-art software and instrumentation
2016
12th International Conference on Biology and Synchrotron Radiation (BSR)
The International Biology and Synchrotron Radiation (BSR) meetings are held every three years with the aim of presenting and discussing state of the art applications in relevant research fields. BSR is a unique forum to discuss the novel possibilities of synchrotrons and X-ray lasers and to promote their applications to challenging biological problems.
EXAFS 2016 - SSRL Summer School on Synchrotron X-Ray Absorption Spectroscopy
SSRL will conduct the 2016 SSRL Summer School on Synchrotron X-Ray Absorption Spectroscopy between July 18 and July 22. The five-day session will provide training in XAS and Imaging theory, experimental design, data acquisition strategies and FEFF based EXAFS data analysis useful to both new and experienced users.
XRS 2016 - 8th SSRL School on Synchrotron X-Ray Scattering Techniques
This school will provide a practical users' guide to planning and conducting scattering measurements at SSRL beam lines, and will cover important techniques including small angle scattering, thin-film scattering, powder diffraction, structure refinement and surface x-ray scattering.
RapiData 2016 at SLAC - Data Collection and Structure Solving: A Practical Course in Macromolecular X-Ray Diffraction Measurement
RapiData 2016 at SLAC is a practical course in macromolecular X-ray diffraction data collection, data processing and structure solution. The aim of the course is to educate and train young scientists in data collection and processing methods at synchrotron beamlines, using state-of-the-art software and instrumentation
2015
2014
2014 SMB Imaging Summer School
The 1st SSRL SXRMI (Synchrotron X-ray MicroXAS Imaging) School will provide a practical users' guide to planning and conducting microXAS imaging experiments at SSRL beam lines. Students will participate in hands-on sessions at the beam lines, including on the following facilities: hard x-ray microXAS imaging (BL2-3), hard x-ray mesoprobe XAS imaging (BL10-2), and the newest microXAS imaging "tender" energy beam line (BL14-3).
2014 International Year of Crystallography
The International Year of Crystallography 2014 (IYCr2014) commemorates not only the centennial of X-ray diffraction, which allowed the detailed study of crystalline material, but also the 400th anniversary of Kepler's observation in 1611 of the symmetrical form of ice crystals, which began the wider study of the role of symmetry in matter.
2013
2013 SSRL Summer School on Synchrotron X-Ray Absorption Spectroscopy
The school will consist of two sets of parallel sessions, one covering basics of XANES and EXAFS data collection, FEFF based analysis and interpretation and the other covering advanced topics in data analysis, FEFF based near-edge analysis and DFT approaches to XANES data. The first curriculum will be suitable for beginner level participants, who have little or no practical experience with EXAFS data collection and analysis. The second curriculum is designed around the needs of participants who already have some experience with data collection and FEFF based data analysis and wish to learn more about approaches to data analysis for more challenging problems.
RapidData Collection & Structure Solving
Synchrotron radiation has become an indispensable tool for many macromolecular crystallography groups. Some synchrotron-specific skills are difficult to learn without ones having an intensive hands-on training program. But not all research groups have the luxury of providing long training sessions for students and postdocs. To provide such an educational experience, we have designed a course in Rapid Data Collection and Structure Solving.
Biological Small Angle X-ray Scattering Workshop
The SSRL Structural Molecular Biology Group hosted a 3-day comprehensive workshop on the use of non-crystalline small-angle x-ray scattering and diffraction techniques in structural biology research.
2012
Structural Molecular Biology Summer School 2012
The structural molecular biology (SMB) summer school 2012 will be held at SSRL between July 16th-20th and will focus on the following disciplines: Macromolecular Crystallography, Small Angle X-Ray Scattering, X-ray Absorption Spectroscopy, X-ray Fluorescence Imaging and X-ray Emission Spectroscopy. The goal of the summer school is to disseminate information about scientific opportunities in synchrotron techniques applicable to biologically relevant systems and to train the participants at both the beginners and expert level to successfully plan, execute and report their research at SSRL.
2012 SSRL Workshop on XAS and RIXS Data Analysis Using CTM4XAS and CTM4RIXS
A two-day workshop on the fundamental aspects of x-ray spectroscopy, including lectures and tutorials on the use of CTM4XAS and CTM4RIXS will be held on June 28-29th, 2012. The first day will focus on lectures and demonstrations by Prof. de Groot. The second day will be dedicated to advanced data analysis session on participant-driven topics. Participants should indicate in the registration form if they are interested in availing of this option and if they would like to bring specific data sets for discussion on the 29th.
Biological SAXS Symposium - A Tribute to Dr. Hiro Tsuruta
A symposium on biological small angle x-ray scattering is being held at SLAC on February 9, 2012 as a tribute to Dr. Hiro Tsuruta, who for almost 20 years led the development and operation of the Stanford Synchrotron Radiation Lightsource structural biology SAXS (bioSAXS) beam line 4-2 facility. BL4-2 is one of the most highly performing and productive experimental facilities in the world today, and has become a beam line of choice for weakly scattering and challenging biological systems.
2011
Synchrotron X-Ray Absorption Spectroscopy Summer School
SSRL conducted a the Summer School on Synchrotron X-Ray Absorption Spectroscopy on June 28- July 1. The goal of the four-day school was to provide, training in theory, experimental design, data acquisition strategies, and data analysis that was useful to beginners and advanced students. Transition Metal K-edge XANES analysis for electronic structure determination and EXAFS analysis for geometric structure determination applicable to relevant systems in the field of Biology, Environmental Science, Catalysis and Material Science will be covered.
SSRL Workshop on XAS and RIXS Data Analysis Using CTM4XAS and CTM4RIXS
A full day lecture and hands-on analysis session on Charge Transfer Multiplet Calculations for X-ray Absorption Spectroscopy (CTM4XAS) will be held at SSRL/SLAC on May 24, 2011. CTM4XAS is a semi-empirical program to analyze transition metal L- and M-edge transitions by evaluating the effects of crystal field and charge transfer parameters on the atomic multiplets. CTM4RIXS is an interactive tool that calculates the two-dimensional Resonant Inelastic X-ray Scattering (RIXS) planes within the charge transfer multiplet model developed in the CTM4XAS software.
2010
Structural Molecular Biology Low-Z XAS Summer School 2010
The goal of the SSRL SMB XAS Summer School was to disseminate information about the scientific opportunities in low-energy XAS applications and train participants on the theoretical aspects and practical data analysis of different experimental techniques. The Summer School focused on low-energy (2.4-4 keV) XAS, in particular S K-edge spectroscopy and imaging.
Sixth International Workshop on X-ray Radiation Damage to Biological Crystalline Samples
This series of workshops was originally concerned with the effects of radiation damage during investigation of protein structures by X-ray crystallography. Other techniques of structural biology are now being included to ensure greater information exchange. The workshop will therefore be of interest to all those using ionising radiation to examine biological structures at the molecular and cellular level.
2009
SSRL Structural Molecular Biology Summer School 2009
The biennial SSRL Structural Molecular Biology (SMB) Summer School provides a lecture series and practical application workshops on biological scientific applications of synchrotron radiation. The goal of the school is to disseminate information about the scientific opportunities in synchrotron radiation applications and train participants on the theoretical aspects, data acquisition and practical data analysis of different experimental techniques.
Workshop on Small-Angle X-ray Scattering and Diffraction Studies in Structural Biology
The SSRL Structural Molecular Biology Group hosts this comprehensive workshop on the use of primarily non-crystalline small-angle x-ray diffraction techniques in structural biology research. The main focus of the workshop is solution x-ray scattering studies on biological macromolecules.