Support us | Visit us | Contact us
X-ray image of a human handing holding an egg containing a map of the molecule, lysozyme, of which egg-white consists. Dr A Barty.
Satellite meeting organised by Professor John Spence and Professor Henry Chapman
This meeting brings together leaders in the development of new techniques for the study of molecular structure and interactions in biology using the recently invented hard X-ray laser. Topics will include time-resolved protein nanocrystallography, femtosecond wide-angle X-ray diffraction, sample delivery devices, data analysis and diffraction theory, and detector systems.
Biographies of the organisers and speakers are available below and you can also download a programme (PDF). Recorded audio of the presentations will be available on this page after the event.
This is a residential conference, which allows for increased discussion and networking. It is free to attend, however participants need to cover their accommodation and catering costs if required.
This meeting is now fully booked. To request a place on the waiting list, please contact the events team
Participants are also encouraged to attend the related scientific discussion meeting X-ray lasers in biology which immediately precedes this event.
Enquiries: Contact the events team
Professor John Spence, Arizona State University and Lawrence Berkeley Laboratory, USA
John Spence is Regent's Professor of Physics at Arizona State University (where he teaches condensed matter physics) with a joint appointment at Lawrence Berkeley Laboratory. He completed his PhD at Melbourne University in Physics in 1973 and a post-doc at Oxford University in Materials Science. He was awarded the Burger Medal of the American Crystallographic Association in 2011, and the Distinguished Scientist and Burton awards from the Microscopy Society of America. He is a Fellow of Churchill College Cambridge, of the APS and of the IOP in the UK. He was co-editor of Acta Cryst A for a decade, and is the author of texts on high-resolution electron microscopy (4th edition in press) and (with J.M. Zuo) on electron microdiffraction. A Festschrift volume of Ultramicroscopy appeared in 2011. John's lab at ASU has developed new scientific instruments and detectors for electron diffraction and imaging, and, since 2004 hydrated bioparticle delivery devices for X-ray lasers (with B. Doak and U. Weierstall). His current interests are biophysics and diffraction physics for the analysis of XFEL data. John is a member of the DOE's BESAC committee, which oversees research at the six US national laboratories.
Professor Spence gratefully acknowledges the award from the US National Science Foundation's Science and Technology Center for the use of X-ray lasers in Biology in support of this meeting.
Professor Henry Chapman, Center for Free-Electron Laser Science, DESY, Hamburg and University of Hamburg, Germany
Henry Chapman is one of the founding directors of the Center for Free-Electron Laser Science (CFEL) at DESY and the University of Hamburg. He led the development of coherent X-ray imaging and phase retrieval using short-pulse coherent X-ray sources, such as free-electron lasers. His interest in this field began as a postdoc, collaborating with David Sayre on how to reconstruct images from the diffraction pattern of a non-periodic object. At Lawrence Livermore National Lab he led a team to develop ab initio three-dimensional coherent diffractive imaging and single-particle imaging. Using novel instrumentation of his design, the team made the first demonstration of imaging by “diffraction before destruction” at the FLASH soft X-ray FEL in Hamburg. He invented and demonstrated a method, called time-delay femtosecond holography, to measure the X-ray induced Coulomb explosion to determine the limits of outrunning radiation damage. When the Linac Coherent Light Source opened in 2009 he led a large international collaboration to continue this work to the atomic scale with the method of serial femtosecond X-ray crystallography. His current research is focused on developing this method and extending it to the smallest possible crystals: that is, single molecules.
Professor Ian Robinson, University College London, UKChair
Ian Robinson is a professor in the Condensed Matter and Materials Physics (CMMP) department at UCL and the London Centre for Nanotechnology (LCN). His research is based in the Research Complex at Harwell to develop phase modulation technology for X-ray imaging and he has a Diamond Professorial Fellowship for imaging chromosomes by coherent X-ray diffraction. His research makes extensive use of synchrotron radiation at the Diamond Light Source and elsewhere. He built a beamline at Brookhaven to develop Surface X-ray Diffraction and a second one at Argonne for Coherent X-ray Diffraction. One outcome of the work was the discovery of Crystal Truncation Rods, for which he was awarded the Surface Structure Prize in 2011.
Dr Abbas Ourmazd, University of Wisconsin-Milwaukee, USAStructure, conformations and dynamics from random snapshots
Abbas Ourmazd, a graduate of Oxford University, is Distinguished Professor of Physics and Electrical Engineering at the University of Wisconsin-Milwaukee. His current research interests include recovery of structure and dynamic from ultra-low signal, random sightings, with implications for physics, biology, signal processing, and machine learning. He has held academic appointments at Oxford, Göttingen, and Brandenburg, and has been Head of Microphysics at Bell Labs, Director of the IHP (a German national laboratory), and Vice Chancellor for Research and Dean of the Graduate School in Wisconsin. He has also launched and led two high-tech startups. His awards have included an Alexander-von-Humboldt Fellowship, and the Johnson-Matthey prize. He is the author/co-author of over 130 publications, holder of 10 patents, and Fellow of the American Physical Society.
Cryo-EM now routinely produces low-dose snapshots of biological objects. The advent of the X-ray Free Electron Laser has made it possible to record diffraction snapshots with intense short pulses before the onset of radiation damage. In both cases, each snapshot stems from an unknown orientation of a weakly scattering object at a poorly defined time-point along its dynamic trajectory. This presentation describes a new generation of algorithms with the potential to recover the structure, conformations, and time evolution of single particles from ultralow signal XFEL and cryo-EM snapshots.
Co-authors:P Schwander, R Fung, A Hosseinizadeh, and A Dashti
Dr Harry Quiney, University of Melbourne, AustraliaObservation and modelling of long-range electronic correlations in femtosecond nanocrystallography
Harry Quiney has a background in Theoretical Chemistry (MSc Monash University) and Relativistic Quantum Electrodynamics (D Phil University of Oxford). He was Senior Research Fellow of the Royal Commission for the Exhibition of 1851, EPSRC Advanced Fellow at the Clarendon Laboratory and Lecturer in Chemistry at Wadham College, Oxford. He is currently Deputy Director of the ARC Centre of Excellence for Coherent X-ray Science and Reader in Theoretical Condensed Matter Physics at The University of Melbourne. Most of his career has been spent investigating relativistic, quantum electrodynamical and weak-interaction effects in atoms and molecules and high-precision spectroscopic tests of physical theories beyond the Standard Model. His current research interests include the design of phase retrieval algorithms for X-ray imaging applications, the fundamental interaction physics of biomolecular imaging using femtosecond XFEL sources and the development of quantum many-body theories.
We have recently observed an abrupt change in the diffraction pattern of crystalline C60 that is initiated by intense femtosecond X-ray illumination using the LCLS XFEL source. This change in the scattering characteristics is attributable to a reduction in the symmetry of the electronic structure over a femtosecond timescale that is too brief in duration to allow any significant nuclear rearrangement. We have been able to fit the diffraction data to a crystallographic model by allowing the electronic structures of the C60 molecules to polarize under the influence of an internal electric field that is characteristic of long-range correlations within the crystal. In order to determine whether this modification to the electronic structure can be regarded as static or in a dynamic equilibrium between symmetry-equivalent configurations, an electrodynamical model has been constructed to simulate the temporal evolution of the coherent electronic structure from a random distribution of electronically excited molecular states. We find that an initial state consisting of a periodic array of C60 molecule ions in randomly-allocated electronic states evolves on a femtosecond timescale into a coherently polarized structure under the influence of long-range internal electronic correlations. The dominant electronic structure of the crystal during the interaction with the femtosecond XFEL pulse corresponds to the observed experimental diffraction pattern and to the empirical crystallographic model that has been used to fit the data. We will also report on recent observations of radiation-induced modification of the electronic structure of β-hematin in nanocrystallographic experiments using XFEL sources.
Dr Duane Loh, SLAC National Accelerator Laboratory, USAWill single particle structural imaging be possible with X-ray free-electron lasers
Duane Loh is interested in developing computational tools that integrate incomplete but statistically compatible data sources. For his PhD, Duane worked with Professor Veit Elser (Cornell University) to develop robust reconstruction algorithms for single particle x-ray imaging using only very noisy and incomplete single particle diffraction data. Through a large international collaboration, Duane has been involved in experiments that use x-ray free-electron lasers to image sub-micron aerosols in flight, disordered aggregation of nanoparticles, and nucleation phenomena of supercooled water. He later extended this work to implement a novel diagnostic of extraordinarily intense x-ray pulses using aerosol nanospheres.
Reconstruction algorithms have demonstrably recovered the three-dimensional structure of biologically relevant objects from noisy and incomplete two-dimensional diffraction patterns from single copies of the object, both in simulations and experiments. These algorithms, however, do not consider random sample injection and are frustrated by the resultant computational demands by an overwhelming stream of largely spurious patterns. This is a pressing computational challenge in three-dimensional imaging.
In this talk, I will share intuition and strategies to differentiate, from many spurious patterns, a subset of weak diffraction patterns actually due to the object of interest. I will also discuss other expected hurdles on the path towards three-dimensional single-particle structural imaging with X-ray free-electron lasers.
Dr Michael J Bogan, Stanford PULSE Institute, SLAC National Accelerator Laboratory, USAChair
Dr Bogan is a Staff Scientist in the PULSE Institute at the SLAC National Accelerator Laboratory. He completed his PhD in chemistry at Simon Fraser University, British Columbia, Canada and was an NSERC Postdoctoral Fellow at Lawrence Livermore National Laboratory. He has a passion for wandering along non-traditional research interfaces and building enabling technology. His research group currently studies the structure and dynamics of (bio)aerosols and protein nanocrystals with ultrafast lasers. Over the last decade, he has helped pioneer femtosecond X-ray diffractive imaging, a new method utilizing the recently operation X-ray free electron lasers, like the Linac Coherent Light Source, that has extended X-ray microscopy to the femtosecond time domain and atomic resolution. Dr Bogan’s research has resulted in over 55 peer-reviewed publications, book chapters and patents. His research has been cited over 1200 times and he has given over 30 invited seminars. His research at the Stanford PULSE Institute has been supported by the US Department of Energy Office of Science Basic Energy Sciences through the AMOS program of CSGB and the Linac Coherent Light Source, the SLAC Laboratory Directed Research and Development program, and the Human Frontier Science Program.
Dr Anton Barty, Center for Free-Electron Laser Science, GermanyWhen crystals meet single particles
Anton Barty is a senior researcher at the Center for Free Electron Laser Science at DESY in Hamburg, Germany, currently working on methods for biological structure determination using X-ray free electron lasers. From 2001-2008 he worked at Lawrence Livermore National Laboratory developing advanced imaging techniques including coherent diffraction imaging, phase contrast imaging and semiconductor lithography. He received his PhD from the University of Melbourne, Australia, in 2000 for the development of phase contrast imaging techniques for optical and electron microscopy.
The unprecedented peak power provided by X-ray free electron lasers enables the study of sub micron sized protein crystals using the principle of diffraction before destruction. Coherent illumination across the entire crystal, which in some cases may consist of only a few unit cells on each side, opens up the possibility of studying nanocrystal diffraction using techniques originally developed for single particle analysis. We will describe developments in mapping the three-dimensional diffraction space produced by nanocrystals and its application to structural analysis using data measured at LCLS.
Dr Robert Stroud, UCSF, USAChair
Robert M Stroud obtained his BA and MA from Cambridge, his PhD from J D Bernal’s laboratory at the University of London where he pioneered early non-centrosymmetric direct methods in crystallography. His postdoctoral with R E Dickerson at Caltech gave the first structures of trypsin and trypsinogen. As Professor of Chemistry at Caltech, he first determined the profile structures of the neurochemical acetylcholine receptor. Since 1977 he is Professor of Biochemistry and Biophysics at UCSF. In enzymology he determined atomic structures and mechanisms, and principles for drug discovery aimed at enzymes and membrane proteins. These include trypsin, thymidylate synthase, HIV protease, and HIV integrase, phosphoregulation, RNA specificity and mechanism of pseudo-uridine synthases, and RNA methylases. With membranes he defined the structural basis of SRP mediated targeting of signal-directed targeting to and through the translocon in the membrane. He discovered the first atomic structures and mechanisms of aquaporins, ammonia transporters, and human Rh factors. He determined the mechanisms and structures of the unfolded-protein receptor Ire1, phosphate and calcium transporters. Stroud is a member of the National Academy of Sciences, fellow of the American Academy of Arts and Sciences and a Fellow of the Royal Society of Medicine (UK).
Dr Thomas White, Center for Free-Electron Laser Science, GermanyProcessing of FEL crystallographic data
Thomas White received his PhD from the University of Cambridge in 2009, where he worked on electron crystallography. Since then, he has been employed at the Center for Free-Electron Laser Science (CFEL) at DESY in Hamburg. He has been developing data analysis methods for serial femtosecond crystallography since the first experiments at LCLS in 2009, and leads the development of the software suite "CrystFEL" which provides specifically for the analysis needs of this new technique.
The availability of suitable processing software for data acquired using the method of serial femtosecond crystallography (SFX) is an important contribution to the development of structural biology using free-electron lasers. Since early 2012, the open-source software suite CrystFEL has been freely available for this purpose and under continuous development as new understanding emerges about the characteristics of SFX data compared to data from more conventional crystallographic data acquisition techniques.
In this talk, I will describe some of the main issues surrounding data processing for data acquired using SFX. Special challenges arise which are unique to this data acquisition methodology, and I will discuss some recent developments in overcoming them.
Dr Rick Kirian, Center for Free-Electron Laser Science, GermanyMethods for phasing coherently illuminated nanocrystals
Rick Kirian joined the Center for Free-Electron Laser science at Deutsches Elektronen-Synchrotron as a post-doctoral researcher in Professor Henry Chapman's group in 2012. He received his PhD in physics from Arizona State University in 2011, under the supervision of Regent's Professor John Spence. Since the beginning of his PhD studies in 2007, he has participated in numerous diffraction experiments at synchrotron and FEL x-ray sources, with an emphasis on femtosecond nanocrystallography and intensity correlation methods. He is presently developing data-analysis techniques and instrumentation related to XFEL diffraction experiments.
Diffraction patterns from femtosecond protein nanocrystallography experiments performed at x-ray free-electron lasers contain measurable intensity in regions that lie between Bragg peaks. The extra information contained in inter-Bragg intensity measurements presents a unique opportunity to determine diffraction phases ab initio, and hence to retrieve the electron density of the molecules that compose the crystal. In order to realize this goal, we are developing iterative phase retrieval algorithms and methods for processing the continuous diffraction from size-varying nanocrystals. In this talk I will present an overview of these ongoing efforts.
Co-authors:Richard Bean, Oleksandr Yevanof, Kenneth Beyerlein, Thomas White, Anton Barty, Henry Chapman
Dr Frank von Delft, University of Oxford, UKChair
Frank von Delft is jointly Principal Investigator of the Protein Crystallography group in the Structural Genomics Consortium (SGC) at Oxford University, as well as Principal Beamline Scientist of beamline I04-1 at Diamond Light Source. After his PhD in protein crystallography with Tom Blundell in Cambridge, he has focused on methodology and high throughput techniques for crystallography, first in San Diego (academically at JCSG, and industrially at Syrrx, Inc), and since 2004 at the SGC, where his group has to date helped solve over 600 crystal structures of human proteins. In late 2012 he set up the partnership with Diamond, in order to set up beamline I04-1 as a user facility for routine medium-throughput fragment screening by X-ray structures. His broader research project is to establish how X-ray structures can be turned into a routine and predictive (rather than occasional and retrospective) tool for generating novel chemistry for targeting proteins.
Dr Dilano Saldin, University of Wisconsin-Milwaukee, USAStructure from an ensemble of multiple randomly oriented particles
Dilano Saldin is a Professor of Physics at the University of Wisconsin-Milwaukee in the US. He obtained his D. Phil. from the Materials Department of University of Oxford in the UK in 1975. He served for a couple of spells as a postdoc in both the Departments of Materials and Engineering Science at Oxford, which he held concurrently with positions of Junior Research Fellow at Wolfson College, and Lecturer in Solid State Physics at Brasenose College. He moved on become a Research Fellow in Solid State Theory group of the Blackett Laboratory of Imperial College, London from 1981-1988. He joined the Physics Department of the University of Wisconsin-Milwaukee in 1988 as an Assistant Professor, and has been there ever since. He is an author or coauthor of some 140 scientific papers, and was elected a Fellow of the American Physical Society in 2012.
The published quality of images of single molecules or viruses reconstructed from experimental XFEL data seems to lag behind those and from simulations. We investigate the cause. For example the requirement that a single particle in an aqueous environment be hit by the XFEL beam may be quite difficult to achieve. If the particle concentration is made so low to allow this, the scattering signal from the particle may be drowned by the scattering by the solvent. On the other hand, increasing the particle concentration may mean that more than a single particle is hit. We describe an approach to analyzing an ensemble of XFEL measurements which may allow the reconstruction of single particle structure from diffraction patterns from multiple randomly oriented particles. We illustrate the theory with the reconstruction of icosahedral and helical viruses. Another circumstance which admits a solution is when a structure sought is a small deviation from a known structure as in time-resolved experiments. We show that it is possible to recover difference electron densities from randomly oriented single proteins.
Professor David Stuart FRS FMedSci, Diamond Light Source & Wellcome Trust Centre for Human Genetics, UKChair
Professor David Stuart FRS FMedSciis MRC Professor of Structural Biology at the University of Oxford, Director of Life Sciences at Diamond, and Director of Instruct. His principal research interests include the structure of viruses and viral proteins as well as cellular proteins, especially those that interact with viruses. In addition to studying the structure, function, and evolution of a range of viruses he has recently, using in silico and synchrotron methods, worked to design safe and effective recombinant vaccines, initially for foot-and-mouth disease virus, which remains the greatest global plague of livestock.
Professor Stuart completed his first degree in Biophysics at King's College, London, and followed this with a PhD and postdoctoral study in the Biochemistry department at Bristol. He then moved to the University of Oxford where he has been MRC Professor of Structural Biology since 1995, and is now Joint Head of the Division of Structural Biology in the Department of Clinical Medicine. He became Director of Life Sciences at Diamond in 2008 and is a Fellow of the Royal Society and the Academy of Medical Sciences.
Dr Andrew Martin, ARC Centre of Excellence for Coherent X-ray Science, School of Physics, University of Melbourne, AustraliaNew methods for analysing nanocrystal and single-particle diffraction
Dr Martin works at Centre of Excellence for Coherent X-ray Science at the University of Melbourne. He works on the development of new coherent diffractive imaging techniques for single particles and nanocrystals. He also works on structural dynamics induced by the X-ray beam and the implications for imaging experiments. Previously he worked at the Centre for Free-Electron Laser Science (CFEL) in the group of Dr Henry Chapman, where he participated in many serial crystallography and single particle imaging experiments at the Linac Coherent Light Source. His roles in the experimental team included data analysis and processing. He obtained his PhD from the University of Melbourne in electron scattering theory in the context of electron microscopy under the supervision of Professor Leslie Allen, with whom he still collaborates on direct (non-iterative) coherent diffractive imaging methods.
In many ways, the extent of our theoretical knowledge about coherent diffraction determines the scope of current experiments and directs our efforts toward future goals, like studying single biological molecules. A collection of theoretical results will be presented for non-periodic and nanocrystalline samples with the goal of measuring basic parameters, like size or orientation, or to aid the ongoing development coherent imaging algorithms and structure determination methods. Some of the issues discussed are missing data due to the detector geometry, the impact of radiation damage and the variable surface configurations of nanocrystals.
Dr Jan Kern, Lawrence Berkeley National Laboratory, USADetectors for X-ray lasers
Jan F Kern obtained his Ph.D. in 2005 in the group of Athina Zouni at the Technical University Berlin. Upon completion of his doctoral studies, Kern remained in the Zouni lab as a postdoctoral fellow until 2008. He was a Feodor Lynen Postdoctoral Fellow with Kenneth Sauer and Vittal Yachandra at LBNL from November 2008 until October 2010, and was a joint postdoctoral fellow between the Yachandra/Yano Lab at LBNL and the Bergmann Lab at SLAC, Stanford University, using X-ray spectroscopy to study the Mn4Ca cluster in Photosystem II until 2012. In late Spring 2012, Kern was promoted from a postdoctoral fellow to a research scientist being jointly employed both at LBNL SLAC. He focuses on the combination of spectroscopic and structural studies on Photosystem II and water oxidation catalysts using synchrotron sources and the LCLS
Our ability to harness the advances in microelectronics over the last decade(s) for X-ray detection has resulted in significant improvements in the state-of-the-art. Biology with Free Electron Lasers (FELs) present daunting detector challenges: all of the photons arrive at the same time, and individual high peak power pulses must be read out shot-by-shot. Direct X-ray detection in silicon pixel detectors – monolithic or hybrid – are the standard for FELs today. This talk will compare different detector implementations, and discuss both fundamental and practical limitations (and what might be done to overcome them) inherent in today’s detectors. The goal is elicit discussions on detector needs (and what tradeoffs might be required) rather than to suggest a specific solution.
Dr Keith Hodgson, Stanford University, USAChair
Keith Hodgson serves Stanford University as the David Mulvane Ehrsam and Edward Curtis Franklin Professor of Chemistry, and is Professor of Photon Science and Chief Research Officer at the SLAC National Accelerator Laboratory, a US Department of Energy research facility. Hodgson served as SSRL Director from 1998 until 2005, helping to realize a major upgrade to SLAC’s venerable synchrotron light source facility, and the genesis of the Linac Coherent Light Source, the world's first hard X-ray laser and the next generation in light source technology. Since 1973, Hodgson has pioneered research in both the use of synchrotron X-rays to determine the crystal structures of proteins, and the development of X-ray absorption spectroscopy to study biological and chemical systems. Since then he has published extensively on X-ray spectroscopic and crystallographic techniques, as well as using those and other techniques to further the study of a large range of biological, bioinorganic and inorganic systems. Hodgson received the EO Lawrence Award from the Department of Energy in 2002, was named a Fellow of the American Association for the Advancement of Science in 2006, and elected to the National Academy of Sciences in 2011.
Professor K Yamauchi, Osaka University, JapanNanofocusing of X-ray free electron laser for coherent X-ray science
Professor Kazuto Yamauchi received his PhD from Osaka University, Japan in 1991. He worked as a Research Associate at Osaka University from 1984, and as an Associate Professor from 1992. He has occupied the professor position at Osaka University since 2003 and, has been a Leader of Center of Excellence for Atomically Controlled Fabrication Process of Osaka University established as a prestigious research and education center by the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) since 2008. He is the primary member of Japan Society of Precision Engineering (JSPE), the president of Kansai branch of the JSPE from 2013, and the chairman of the Expert Committee for Ultra-precision Machining of the JSPE from 2006. He organizes an annual X-ray optics conference in United States as a corresponding member of the International Society for Optics and Photonics (SPIE). He is working in the field of precision fabrication for optical and electronic devices, and is studying to realize atomically controlled and free-formed surfaces. In the X-ray optical system development, he produced the atomic precision optical devices for hard X-rays, and realized an X-ray nanoprobe with the diameter of sub-10nm which was the smallest X-ray beam human-made and was used for synchrotron radiation based X-ray microscopy and/or spectroscopy.
Professor Kazuto Yamauchi has published more than two hundred papers in peer reviewed international journals, more than hundred contributed and invited presentations in international conferences, and review articles in the field of X-ray optics development and semiconductor surfaces processing. He was given the Best Original Paper Award by JSPE in 2000.
X-ray free-electron lasers produce intense femtosecond pulses, which have applications in exploring new frontiers of coherent X-ray diffraction imaging. In particular, in biomedical sample imaging, extremely short pulses can be used to visualize nanostructures without radiation damage, which is of critical importance but has never been achieved using synchrotron ring facilities. The unique characteristics of X-ray free-electron laser radiation can be enhanced signiﬁcantly using focusing optics. Here we present reﬂective optics comprising elliptically ﬁgured total-reflection mirrors with nanometer accuracy for preserving a coherent wavefront, and successfully focus a 10 keV X-ray free-electron laser on areas of 1 mm and less than 50 nm. The peak power density reached a value of 1020 W/cm2. This achievement can be applied to realize the further condensation of an X-ray free-electron laser by employing a highly accurate multilayer mirror. Our focusing optics are expected to play a crucial role in the advance of microscopic research towards achieving ultimate resolution, as well as in the development of nonlinear optical sciences under extreme conditions. The current status and future challenges of the X-ray free electron laser optics development will be outlined with discussion of the mirror design, fabrication, and wavefront measurement methods.
Dr Kristoffer Haldrup, DTU-Physics, DenmarkAnalysis of X-ray diffuse scattering in X-FEL experiments – opportunities, challenges and strategies
Working at Risø National Laboratory in Denmark, Kristoffer Haldrup obtained his PhD degree from the Niels Bohr Institute in 2007. After the thesis work, he moved on to become a Postdoc at the “Centre for Molecular Movies” a Danish Centre of Excellence then located at the University of Copenhagen. Here he initially worked on X-ray characterization of structure and dynamics in organic thin films for photo-voltaic applications but also on developing methods for the quantitative analysis of X-ray Diffuse Scattering data from ultrafast experiments on liquid-phase photochemistry. In 2011-2012 Kristoffer Haldrup, funded by the VKR/Carlsberg foundations, worked with Prof. Lin X. Chen at Argonne National Laboratory near Chicago, focusing on X-ray Absorption measurements in the ultrafast regime and on analyzing data from multi-modal MHz repetition-rate experiments. Returning from Chicago to the Centre for Molecular Movies, now at the Technical University of Denmark, he is now mostly working on data analysis and interpretation of photochemistry experiments conducted at the new X-FEL sources. When not working with X-ray data analysis, he tries to find as much time as feasible for travels to places where skiing, hiking and diving are possible.
This presentation details some of the challenges and opportunities encountered when utilizing ultra-bright pulses of X-rays for X-ray Diffuse Scattering experiments on solution-phase chemistry on femtosecond time scales. In particular, the use of Singular Value Decomposition as a tool for detecting and removing highly variable (pulse-to-pulse) background contributions is discussed. These efforts have been motivated by the recent arrival of X-ray Free Electron Lasers, where the unique beam characteristics of these facilities have opened up new possibilities for research at the ultrashort time scales, including structural investigations of photo-chemical reactions in liquids.
Professor Bruce Doak, Max-Planck-Institut fur Medizinische Forschung, Germany and Arizona State University, USAChair
Bruce Doak is a leading international expert on the use of microscopic liquid free-streams to deliver fully hydrated biological species (nanocrystals, viruses, macromolecular complexes) into x-ray beams under vacuum. His injector development was carried out in conjunction with Uwe Weierstall and John Spence at ASU, culminating in the GDVN injector that is now the mainstay injector for hydrated biological imagining with XFEL’s. One GDVN patent has been issued and several others are pending. Doak has been a professor of physics at ASU since 1991, before which he spent a decade as a principal investigator at Bell Laboratories in Murray Hill, NJ. He holds degrees from Cornell University (BS) and MIT (MS, PhD). His “predoctoral” work at the Max-Planck-Institut für Strömungsforschung in Göttingen (seminal development with Peter Toennies of inelastic helium atom scattering to measure surface phonon dispersion curves) was recognized with an Otto-Hahn award. The use of molecular beams to study and modify solid surfaces (and even vice versa) formed the core of his subsequent research and delivered the expertise with gaseous free-jets that was vital to GDVN development. Doak is currently on sabbatical leave at the Max-Planck-Institut für medizinische Forschung in Heidelberg, supported by a Marie-Curie Incoming International Fellowship (FP7-PEOPLE-2011-IIF) of the European Union.
Dr Uwe Weierstall, Arizona State University, USALiquid jet injectors for X-ray lasers
Uwe Weierstall has been a research professor at Arizona State University since 2008, and a research scientist there starting in 1998. During the last 7 years he has been working on the development of sample injectors for synchrotrons and XFELs and has been involved in many seminal experiments with biological samples at the LCLS. In addition to his work at the LCLS, which included preliminary experiments with protein nanocrystals in liquid jets at the Advanced Light Source at Berkeley, CA, he has worked on developing instrumentation and methods for scanning tunneling microscopy, electron diffraction and imaging and X-ray coherent diffraction imaging. He received his PhD in Physics from the University of Tübingen in Germany in 1994 for work on electron holography of biological samples.
The emerging method of serial femtosecond crystallography (SFX), which uses ultrashort X-ray pulses from an X-ray free electron laser to outrun radiation damage, has been shown recently to achieve atomic resolution from protein microcrystals. An essential requirement for SFX is a sample delivery method, which can keep up with the repetition rate of the XFEL and provides fresh sample for every X-ray pulse. A liquid jet injector has been developed at ASU for this purpose and allows data collection from hydrated biomolecules and microcrystals at room temperature. In order to use protein microcrystals grown in Lipidic cubic phase (LCP) for SFX experiments, a new approach was needed to generate a stream of the gel-like LCP with tens of micrometer diameter. Therefore a new LCP injector has been developed, which allows the collection of data from a contiguous stream of nanocrystals embedded in LCP. An overview of the current injection devices and recent results will be presented.
Coauthors:Daniel James, Dingjie Wang, John C H Spence, R B Doak, Petra Fromme, Arizona State University, USAMartin Caffrey, Trinity College Dublin, Republic of IrelandVadim Cherezov, The Scripps Research Institute, USA
Dr Thomas Barends, Max-Planck-Institut fur Medizinische Forschung, GermanySFX vs PX: comparing crystallographic data from FELs and synchrotrons
Thomas Barends obtained his PhD in protein crystallography from the University of Groningen in the Netherlands in 2004. Since 2005, he has been working in the department of Biomolecular Mechanisms at the Max-Planck Institute for Medical Research in Heidelberg, Germany. Having previously worked on the structure and mechanism of light sensor proteins he now works on developing techniques for protein crystallography using XFEL sources.
Free-electron lasers (FELs) are pushing back the limits of possibility in protein crystallography. The high-intensity, femtosecond duration pulses afforded by FELs allow data collection from micrometer-sized crystals while outrunning radiation damage. Moreover, FELs may be used for pump-probe experiments with unprecedented time resolution.
However, the intricacies of FEL data collection pose specific challenges: as every FEL pulse destroys the sample, data are mostly collected from a stream of microcrystals and averaged to remove the variations in crystal size and quality as well as shot-to-shot variations in beam parameters. This technique, dubbed serial femtosecond crystallography (SFX) requires specific data processing methods.
Alternatively, data may be collected from a single crystal using an attenuated beam. This, too, requires special processing methods because of the limited sampling of reciprocal space possible in the short duration of the FEL pulse.
We will compare FEL data collected using both methods with comparable data collected using classical methods at synchrotrons, to explore the determinants of data quality in terms of beam and crystal properties
Dr Liz Carpenter, University of Oxford, UKChair
Dr Liz Carpenter is a structural biologist with experience working both with soluble and membrane proteins.
She graduated in Biochemistry from Cambridge, and took her PhD at Birkbeck College London. She undertook post-docs in France, NIMR and Imperial College.
In 2008 Dr Carpenter moved to the Diamond Light Source to establish and run the Membrane Protein Laboratory, an international research and training facility for membrane protein structural biology, for Professor So Iwata. In 2009 she moved to the Structural Genomics Consortium to run the Integral Membrane Protein Group. Her group has recently published two human membrane protein structures, the Progeria related nuclear membrane zinc metalloprotease, ZMPSTE24 (Quigley et al, Science, 2013) and the first human ABC transporter, ABCB10 (Shintre et al, PNAS, 2013). They have also recently deposited the structure of the human ion channel TREK-2.
Professor Martin Caffrey, Trinity College Dublin, IrelandSerial femtosecond crystallography of membrane proteins using the lipidic cubic mesophase
Martin Caffrey grew up in Dublin and was awarded a first-class honours degree in Agricultural Science at University College Dublin in 1972. With an MS in Food Science and a PhD in Biochemistry from Cornell University, Ithaca, New York, he embarked on a professorial career in the Chemistry Department at The Ohio State University, Columbus, Ohio. In 2003, he returned to Ireland to establish a multi-disciplinary programme in Membrane Structural and Functional Biology at the University of Limerick with funding from Science Foundation Ireland and the USA National Institutes of Health. Its mission is to establish the molecular bases for biomembrane assembly and stability and to understand how membranes transform and transmit in health and disease. In 2009, his research group moved to Dublin when Prof Caffrey received a Personal Chair at Trinity College Dublin with joint appointments in the School of Medicine and the School of Biochemistry and Immunology.
The lipid-based bicontinuous cubic mesophase is a nanoporous membrane mimetic with wide ranging applications in areas that include medicine, personal care products, foods, and the basic sciences. An application of particular note concerns it use as a medium in which to grow crystals of membrane proteins for structure determination by X-ray crystallography (1). At least two variations of the mesophase exist. One is the highly viscous and sticky cubic phase which has well developed long-range order. The other, referred to as the sponge phase, is considerably more fluid and lacks long-range order. The sponge phase has recently been shown to be a convenient vehicle for delivering microcrystals of membrane proteins for serial femtosecond crystallography (SFX) at the Linac Coherent Light Source, SLAC National Accelerator Laboratory (2). Unfortunately, the sponge phase approach calls for large amounts of protein which are not always available in the case of membrane proteins. The cubic phase offers the advantage of requiring significantly less protein for SFX but comes with its own challenges. In this talk, I will describe the physico-chemical bases for these challenges, solutions to them and prospects for future uses of lipidic mesophases in the SFX arena.
Co-authors:Dianfan Li, Trinity College Dublin, IrelandVadim Cherezov, The Scripps Research Institute, USAUwe Weierstall, John C H Spence, Petra Fromme, Arizona State University, USA
Dr Bill Pedrini, Paul Scherrer Institute, SwitzerlandXFEL 2D protein crystallography on fixed targets
Dr Pedrini gained his Diploma (1998) and PhD (2002) in Theoretical Physics from ETH Zuerich. 2002-2005: Postdoc,Solid State NMR, ETH Zuerich; 2006-2007: Postdoc, Protein NMR, The Scripps Research Institute, La Jolla, CA, USA; 2008-2009: Staff scientist, Protein NMR, ETH Zuerich and 2010-Present: Staff scientist, SwissFEL Project, Paul Scherrer Institute.
We report on the first X-FEL single shot experiments of bacteriorhodopsin 2D crystals, recently performed at LCLS.The pattern from single crystals are clearly recognized in the diffraction images, and the Bragg peak intensities can be reliably extracted down to resolutions of 6-7 A.
These results are promising, but indicate that substantial progress is necessary to achieve atomic resolution.
Public lecture 5 Dec
Conference 11 Dec
Enter your email address to receive updates about scientific meetings at the Royal Society
Full listing of our events and exhibitions.
Watch videos of past events.
Most of our talks are free and open to the public.
We host major conferences for leading scientists.
Explore our annual science exhibition
Contact the events team.