Instrumentation
Clive R. Bagshaw in Biomolecular Kinetics, 2017
Regarding x-ray sources, the availability of synchrotron radiation sources reduced the time taken to acquire data sets from hours to minutes, compared with standard laboratory sources. Synchrotrons also provided a practical white source (i.e., covering many wavelengths) required for the Laue diffraction method. By using multiple wavelengths, the time to acquire data is considerably shortened. Laue diffraction allows reactions to be followed to the sub-nanosecond time scale [565,569]. More recently, an x-ray-free electron laser, whose peak pulse intensity is many orders of magnitude higher than that from a synchroton, has allowed the sub-picosecond time scale to be explored [430,564,568,569]. Kinetic measurements are achieved using a pump-probe approach, where the reaction of a photoreactive protein is initiated with a visible laser pulse, then the reaction is probed by a short pulse from the x-ray laser (Figure 7.33). The sample comprises a stream of nanocrystals in a liquid jet in continuous flow at constant velocity. The distance between the light activation beam and the x-ray probe beam therefore reflects the time interval, as in the traditional continuous-flow method (Section 7.2.3). The stream of nanocrystals also ensures that diffraction data are built up from crystals with multiple orientations and overcome the problem that each crystal is ultimately destroyed by the x-ray pulse, although not before useful diffraction data are logged by a CCD detector.
Laser Principles in Otolaryngology, Head and Neck Surgery
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Lasers that utilize beams of electrons unattached to atoms and spiralling around magnetic field lines were initially developed in 1977 and are important research instruments. Free-electron lasers are tuneable and, in theory, could cover the electromagnetic spectrum from infrared to X-rays. Free-electron lasers could be capable of producing very high power radiation and may have medical applications in the future.
How, and When, to Effect Collaborations
John R. Helliwell in Skills for a Scientific Life, 2016
So where can one learn about particularly successful collaborations, as a model case study for your planned venture into your first, or next, collaboration? I offer as one such the Centre of Excellence for Coherent X-ray Science (CXS) in Australia funded by the Australian Research Council and the State Government of Victoria. This was led by Professor Keith Nugent for several years and then by Professor Leann Tilley. I was invited to join their international advisory board and served eight years on that and chaired its science advisory committee [4]. This proved to my mind to be an exemplar of why it was needed and how it was executed by all concerned. The collaboration brought together several vibrant individual research areas into a constructive whole approach with the vision to be ‘the world leader in the development of coherent X-ray diffraction for imaging biological structures’. The researchers were from six academic institutions and one research institution, namely the University of Melbourne, La Trobe University, Monash University, Griffith University, Swinburne University of Technology, and the Australian Commonwealth Scientific and Industrial Research Organisation. I whole-heartedly agreed with its short summary assessment: CXS brings together leading Australian researchers in the fields of X-ray physics; the design and use of synchrotron radiation sources; and the preparation, manipulation and characterisation of biological samples. Regarded as a world leader in its field, CXS aims to open a new frontier in biotechnology – the non-crystallographic structural determination of membrane proteins. CXS research is driven by its access to existing third-generation synchrotron light sources and to the Australian Synchrotron. We are also exploring the application to imaging problems of short wavelength highharmonic generation sources and X-ray free-electron lasers that are under development worldwide.
Small-angle X-ray scattering for the proteomics community: current overview and future potential
Published in Expert Review of Proteomics, 2021
Petri Kursula
While technical developments within sample preparation, delivery, measurement, and analysis on synchrotron SAXS beamlines are likely to continue at a rapid pace, it will be interesting to follow at least three additional aspects of the SAXS workflow. Firstly, what role can X-ray free electron lasers play in time-resolved SAXS of biomolecules? Theoretically, it should be possible to follow the kinetics down to the femtosecond timescale. Time-resolved studies on conformational changes induced by post-translational modifications will become possible; thus far, such studies have mainly been done on light-inducible systems [84,85]. Secondly, how can the analysis of SAXS data from membrane proteins be developed and streamlined to produce the most reliable models? Membrane protein complexes are obviously the most coveted targets in integrative structural biology, but they present both practical and theoretical bottlenecks in SAXS analyses. Thirdly, can in-house SAXS instruments be used for high-throughput biomolecular SAXS experiments to an extent that could compete with synchrotron sources, which are currently heavily overbooked and not available to all experimenters? The latter point could lead to a more effective development of local and national lab-based SAXS infrastructures, in addition to international synchrotron sources. A constantly running SAXS facility in the home laboratory allows for effective screening and sample optimization and could be a viable alternative for radiation-sensitive samples. As an important example, it has been demonstrated that SEC-SAXS experiments are possible on an in-house SAXS instrument [31].
An outlook on using serial femtosecond crystallography in drug discovery
Published in Expert Opinion on Drug Discovery, 2019
Alexey Mishin, Anastasiia Gusach, Aleksandra Luginina, Egor Marin, Valentin Borshchevskiy, Vadim Cherezov
The concept of a free electron laser was proposed in 1971 by John Madey at Stanford [25], based on a previously described process of photon generation by free electrons moving in a periodical array of magnets, known as an undulator, by Vitalii Ginzburg [26] and Hans Motz [27]. The first demonstration of FEL-generated infrared radiation was achieved by Madey’s group in 1976, stimulating further intense research work that culminated in commissioning of the first soft XFEL source FLASH (X-ray photon energy <0.2 keV) at DESY in Hamburg in 2005 [28]. A few years later, in 2009, the first hard XFEL (X-ray photon energy up to 10 keV) Linac Coherent Light Source (LCLS) was opened for user experiments at the SLAC National Accelerator Laboratory in Menlo Park, California [29,30].
The role of women scientists in the development of ultrashort pulsed laser technology-based biomedical research in Armenia
Published in International Journal of Radiation Biology, 2022
Gohar Tsakanova, Elina Arakelova, Lusine Matevosyan, Mariam Petrosyan, Seda Gasparyan, Kristine Harutyunyan, Nelly Babayan
The development of ultrashort pulsed electron beam (UPEB) based biomedical research in Armenia became possible after the establishment of CANDLE Synchrotron Research Institute in 2002 where the AREAL (Advanced Research Electron Accelerator Lab) facility was constructed, which is a new laser driven linear accelerator for generating ultrashort relativistic electron pulses for advanced research in the fields of new acceleration concepts, novel radiation sources and applications in ultrafast life and materials sciences. A good perspective of this new approach is the possibility of an incremental upgrade of the facility energy for producing brilliant light via a Free Electron Laser.
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