Released By: Australian Synchrotron
Release Date: Mon 1 December 2008
Asia Oceania Week (A-O Week) promises to be a big week for the Australian Synchrotron as it hosts the third Asia Oceania Forum on Synchrotron Radiation Research (AOFSRR) as part of a full week of activities that includes the annual Australian Synchrotron Users Meeting.
The Australian Synchrotron is one of the latest third generation synchrotrons in the world and is the newest operating synchrotron facility in the Asia Oceania region. Over the next few days, delegates from Taiwan, China, Japan, Singapore, Korea, India, Thailand, New Zealand and Australia will come together at the St Kilda Novotel in Melbourne to hear about developments at the Australian Synchrotron and discuss regional collaboration.
In September this year the Australian Synchrotron passed another milestone clocking up its 1000th user while still only operating at 30% of its current capacity. The numbers of users is expected to rise dramatically as open access to another three new beamlines begins in the New Year.
During A-O Week delegates including the directors and senior scientists from the eleven regional light sources will hear an update on the Australian Synchrotron and share their knowledge and exchange ideas. The annual Users Meeting is an opportunity for researchers to present their work with presentations that will focus on science conducted at the Australian Synchrotron. Many papers have already been published using the first to be established protein crystallography beamline and last week the first two papers using the infra red beamline were published.
During the AOFSRR, presentations will focus on both facility developments in the region and on next generation science. A special theme of the workshops will be the new science which will be performed at the next generation light sources such as Free Electron Laser (FEL) and Energy Recovery Linear accelerators (ERL) facilities.
Professor Robert Lamb, Director, Australian Synchrotron, said "as the newest synchrotron in the region we are generating a lot of interest and this is a great opportunity for our regional colleagues to come and see our progress and for us to promote regional collaboration and develop joint projects".
Professor Yoshiyuki Amemiya, President, AOFSRR, said "it is my hope that this 3rd AOFSRR workshop will continue the development of scientific networks between the user communities of the member countries".
Following is a brief synopsis of some of the synchrotron science to be presented during A-O Week, 1-5 December at the St Kilda Novotel, Melbourne. For more information on A-O Week visit www.a-oweek2008.com
Background Briefing notes on science to be discussed at
ASIA OCEANIA WEEK AT THE AUSTRALIAN SYNCHROTRON
1-5 DECEMBER 2008
PROBING LIQUID SURFACES WITH SYNCHROTRON RADIATION
Liquid surfaces are ubiquitous in biological, industrial and domestic applications. Their behaviour is determined by interactions that occur in the first few molecular layers. Ian Gentle and his collaborators in Australia and Japan have used several synchrotron x-ray techniques to tackle the challenges involved in measuring subtle structural features of thin films. They are looking at organic films that contain porphyrins, which have useful photo-electronic properties. Potential applications of this research include applications in molecular electronics( ie one molecule thick electrical conducting films) and solar cells.
BIOMEDICAL SYNCHROTRON APPLICATIONS - SHOW ME THE METAL
Virtually all metal-containing drugs are pro-drugs, i.e., they are not administered in a biologically active form but are transformed into the active form by the body's normal metabolic processes. To improve drug design, Peter Lay and other researchers around the world are developing methods to follow these drugs from the point of administration to the site of action. Synchrotron x-ray techniques provide unprecedented information on bio-transformations of drugs, toxins and carcinogens, as well as normal biological processes and disease conditions at the molecular and cellular levels. Examples include assessing the potential cancer risks of widely consumed chromium dietary supplements, investigating the mode of action and improved design of vanadium anti-diabetic drugs, and finding out how the gallium anti-cancer drugs used in clinics (or undergoing clinical trials) actually work and how their design can be improved.
CHROMIUM - FRIEND OR FOE?
Although chromium (III) is widely used in nutritional supplements, and there is evidence to suggest there may be some potential toxic effects, little is known about its biological functions and chemistry in biological fluids. In addition, little is known about the behaviour of chromium at the low levels found naturally in the body. A promising method for further studies is synchrotron-based x-ray absorption spectroscopy (XAS), which allows researchers to determine the chemical state of chromium in complex systems, even at low concentrations.
RADIATION THRAPY USING SYNCHROTRONS- Harder on tumours, easier on the patient.
Synchrotron microbeam radiation therapy (MRT) is being considered for clinical use following laboratory trials that showed it was effective against tumours in mice - and that it was less-damaging to normal tissue than conventional radiography. However, the underlying cellular mechanisms are poorly understood. Rob Lewis and his colleagues are trying to find out why tumours are less-resistant to high-dose MRT than normal tissue.
WATCHING THE FIRST BREATH WITH X-RAY IMAGING
Aeration of the lung and the transition to air-breathing at birth is fundamental to mammalian life and initiates major changes in cardiopulmonary physiology. However, the dynamics of this process and the factors involved are largely unknown, because it has not been possible to observe or measure lung aeration on a breath-by-breath basis. The high contrast and spatial resolution of synchrotron 'phase contrast' x-ray imaging have enabled Rob Lewis and his colleagues to study lung aeration at birth in spontaneously breathing neonatal rabbits.
USING SYNCHROTRONS TO WITNESS THE EARLY STAGES OF HUMAN EMBRYONIC STEM CELL (HESC) DIFFERENTIATION
Human embryonic stem cells (HESCs) can be 'differentiated' to produce normal cells that could potentially be used to replace cells damaged through disease. To maximise the potential therapeutic benefit, cells prepared by this method will need to be differentiated towards the specific type of cells required. Fast, accurate and reproducible assays will be needed to validate the efficacy and safety of the HESC differentiation process and 'certify' each batch of differentiated cells prior to transplantation. Phil Heraud and his colleagues have found that synchrotron infrared (FT-IR) microspectroscopy is an extremely sensitive and accurate tool for looking at the very early stages of HESC differentiation and could be developed as an alternative to existing immunofluorescence-based discrimination approaches.
MID FLIGHT OIL: WATCHING BIO OIL SPRAYS WITH SYNCHROTRON X-RAYS
Biomass fuels are a promising alternative to petroleum-based fuels, but we need to know more about how they perform in internal combustion engines. In Australia, the most abundant form of renewable biomass is woody biomass from sugar cane.[ Synchrotron techniques developed in the US by Monash University researchers are being used to probe the fluid mechanics and structure of high-pressure bio-oil fuel sprays (derived from woody biomass) in automotive diesel engines. Optical techniques cannot be used for these studies.
SYNCHROTRON TOMOGRAPHY: LOOKING AT THE MOUSE WHILE THE CAT SCAN'S FAR AWAY
Researchers from Australia, New Zealand and Italy used synchrotron x-ray microtomography and phase contrast imaging techniques to analyse the microarchitecture of trabecular bone and bone soft tissue in a study of osteoporosis in mice. The method yielded high-resolution images that could be used for quantitative assessment, and will facilitate further studies of progressive bone changes - as well as potentially enabling assessment of the therapeutic efficacy of drugs for treating metabolic bone disorders.
RELENZA REVISITED - DESIGNED DRUGS AND DRUG RESISTANCE
The neuraminidase class of anti-influenza virus drugs has now been in use for almost ten years. Experience confirms decade-old predictions about the appearance of drug-resistant variants of the virus.
[BACKGROUND: The ability of synchrotron x-rays to reveal the detailed structures of biological proteins and their interactions enabled researchers to develop a new approach to drug discovery. Rational drug design identifies opportunities to block or modify molecular interactions. The anti-influenza drug RelenzaTM was the world's first structure-based anti-viral drug and an early example of rationally based drug design methodologies. RelenzaTM was developed in the mid-1990s by a CSIRO team led by Peter Colman and Jose Varghese. Colman and Varghese used synchrotron protein crystallography to create a high resolution picture of the neuraminidase protein on the virus surface.]
GAGGING THE HIV VIRUS WITH SYNCHROTRON LIGHT
The main structural component of the protein coat (capsid) that protects the HIV virus is a poly-protein known as Gag. During the formation of a mature, infectious HIV virus, Gag is cut into six parts by another viral protein. Nathan Cowieson and his colleagues used a combination of synchrotron techniques (including small angle x-ray scattering) to investigate the steps involved in cutting Gag, which take place in a very specific order. If we knew how to disrupt the cutting process, we might be able to design treatments that could stop the virus particles maturing.
RECOGNIZING A ROTAVIRUS KILLER BY ITS COAT
Rotavirus is the leading cause of acute childhood gastroenteritis in mammals, especially under the age of five, and is responsible for an estimated 600 000 infant deaths each year. It may be possible to develop therapeutic and preventative measures against rotavirus diarrhoea that work by stopping the virus particle from getting inside a host cell, which it must do before it can replicate. A 'spike' protein in the rotavirus's outermost protein coat (capsid) plays an important role in penetrating the host cell membrane. Synchrotron protein crystallography has shed new light on the interaction between a key part of the spike protein (known as VP8*) and sialic acid bound to the host cell surface.
MAPPING THE DAMAGE OF MALARIA IN THE BRAIN USING SYNCHROTRON LIGHT.
Cerebral malaria (CM) is a devastating complication of the malarial parasite and causes considerable medical, economic and emotional burdens in sub-Saharan Africa and parts of South East Asia. Although CM is responsible for more than one million deaths among children under the age of five each year, the underlying biochemical mechanisms are largely unresolved. Australian researchers are investigating the use of synchrotron infrared mapping and imaging techniques as new tools to study how the disease develops. They want to obtain new information about how the organic and inorganic composition of cerebral tissue alters as a result of tissue damage induced by oxygen deprivation. In CM victims, parasitised red blood cells (and platelets and leucocytes) cluster around the brain microvessels, apparently obstructing the microvessels and reducing the oxygen supply, leading to hypoxia-induced tissue damage.
POLLUTION PROPAGATION IN NORTHERN NSW-NEW CLUES FROM SYNCHROTRONS
Aluminium and iron released from disturbed acid sulfate soils (and possibly also reduced sulfur compounds) have severe environmental consequences for coastal regions in north-eastern Australia - damaging aquatic ecosystems, killing fish, promoting harmful algal blooms and destroying aquaculture. The cost to the Australian economy is estimated at more than $200 million a year. Researchers are using synchrotron techniques such as x-ray absorption spectroscopy (XAS) to obtain detailed information about the characteristics of these elements (including their chemical forms or species) that influence their solubility, reactivity and transport in the environment.
FREEZE-FRAMING MOLECULES WITH SUPER SYNCHROTRON BEAMS.
The ultrafast, ultrabright X-ray pulses offered by a new generation of free-electron lasers will usher in extraordinary new capabilities in x-ray science, with a wide range of applications in fundamental atomic physics, ultrafast chemistry and materials science. Of particular interest is the ability to study transient material dynamics, and ultimately determine the structures of proteins, viruses and macromolecules that cannot be crystallised. Anton Barty and his colleagues are developing experimental methods for x-ray free electron laser diffractive imaging. Exposing a specimen to a FEL pulse produces an x-ray scattering pattern that yields valuable structural information - completely unaffected by the subsequent vaporisation of the specimen as a result of the intense pulse.
PROSPECTS FOR VERY HIGH RESOLUTION IMAGING USING X-RAY FREE ELECTRON LASERS
X-ray free electron lasers (XFELs) are being developed in major projects around the world. The first of these, the Linac Coherent Light Source at Stanford Linear Accelerator Center, is scheduled to come on stream in 2009. Comparable projects underway in Japan and Europe will begin operation in the next few years. XFELs will be around ten orders of magnitude (ten thousand million times) brighter than currently available x-ray sources. With the potential for a transformation in x-ray science comparable to the transformation that occurred in optical sciences with the development of the laser, there will be a wealth of new science emerging from such sources.
FROM PICOSECOND TOWARD FEMTOSECOND TIME-RESOLVED X-RAY SCIENCE
Time-resolved x-ray techniques using the pulsed nature of synchrotron radiation are powerful tools for exploring structural dynamics in materials and biological sciences. Shin-Ichi Adachi and his colleagues apply these capabilities to capture photochemical reaction dynamics in liquid or on solid surfaces, light-induced response of photosensitive protein molecules and cooperative phenomena in strongly-correlated electron systems. Adachi will discuss the current status of picosecond studies and the future prospects of femtosecond science.
[Definitions: A nanosecond is one thousand millionth of a second. A picosecond is one thousandth of a nanosecond. A femtosecond is one thousandth of a picosecond.]
INDUSTRIAL APPLICATIONS AND THE PX/PHARMACEUTICAL CONTRACT BEAMLINE PROJECT AT THE PHOTON FACTORY
At the Photon Factory (PF) in Japan, vigorous efforts have been made in the last eight years to develop and install state-of-the-art protein crystallography beamlines, which are available to industrial users. Currently about 8 % of beamtime on the insertion device beamlines] is used by the pharmaceutical and food industries. The Photon Factory formed a consortium with nine companies (now eight due to a merger) for efficient beamline access and to share information on the latest developments at the PF and elsewhere. The consortium is designed to be flexible and open for other companies to join. A new beamline being constructed in collaboration with a pharmaceutical company will be used for other demanding academic structural biology projects as well. The Photon Factory is now pursuing expansion of industrial use in materials science, and 11 companies are conducting experiments on various beamlines in a new industrial access scheme at the PF.