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Science Highlights
Infrared spectromicroscopic images of brain tissue obtained by the CLS Mid-Infrared beamline. The dark blue mottling representing lipids (fats) in the healthy tissue (left) is largely absent from the GBM tumour (right). Health: Shining Light on Brain TumoursThe Canadian Cancer Society estimates that 2600 new cases of brain cancer will be diagnosed in 2010. Glioblastoma multiforme (GBM) is the most aggressive and malignant form of brain cancer, and attempts to successfully treat GBM tumours depends on identifying tumour cells – both when detecting cancer in biopsies and when ensuring that all of the cancer has been removed after surgery. With the help of the Canadian Light Source, a team led by Dr. Kaiser Ali, a pediatric oncologist in the Saskatchewan Cancer Agency’s Cancer Research Unit and collaborators from the University of Saskatchewan, Saskatoon Health Region, CLS and the National Research Council have been able to identify a chemical signature unique to GBM tumour cells. The pilot study made the front cover of the July 2010 issue of the International Journal of Molecular Medicine. Reference: K. Ali, et al. 2010. Biomolecular diagnosis of glioblastoma multiforme using Synchrotron mid-infrared spectomicroscopy. International Journal of Molecular Medicine 26 pp. 11-16.
Scanning transmission X-ray microscope image of bacterial cells taken at the CLS. The blue dots are iron-containing magnetosomes, each about 30 billionths of a metre in size. Image courtesy of Adam Hitchcock, McMaster University. Materials: Synchrotron takes bearing on nano magnetsSince the late 1960’s, scientists have known that some bacteria make internal compasses by growing tiny magnetic crystals called magnetosomes. The bacteria use them to navigate, with cells of the same species growing crystals of uniform size, structure and out of the same magnetic minerals. Using the Canadian Light Source, researchers have for the first time been able to ‘see’ the magnetism of magnetosomes inside individual bacterial cells using the synchrotron’s X-ray microscope. The finding sheds light on how magnetosomes grow in bacterial cells in response to genetic and environmental factors. Such understanding could be used by researchers to genetically manipulate the bacteria to grow magnetosomes that are tailor made for use in new kinds of data storage devices, nanomachines or delivery systems for cancer chemotherapy and other drug treatments. Reference: Lam, K.P., Hitchcock, A.P. et al. 2010. Characterizing magnetism of individual magnetosomes by X-ray magnetic circular dichroism in a scanning transmission X-ray microscope. Chemical Geology 270, pp. 110-116. DOI: 10.1016/j.chemgeo.2009.11.009
Infrared spectrum of the Orion Nebula (background)—the first taken by the Herschel Space Observatory’s HIFI spectrometer in March, 2010. Infrared spectra taken at the CLS is helping astronomers make sense of spectra obtained by Herschel and other new telescopes. Materials: Synchrotron reaches for the starsInterstellar clouds and other astronomical features are rich sources of organic chemicals. However, the pervasiveness of some molecules, such as methanol, drown out the spectral fingerprints of more exotic chemicals. With a new generation of space observatories and radio telescopes coming online, astronomers are plumbing the chemical depths of space with greater detail than ever before. But they have to be able to weed out the signals from methanol and other common molecules in order to see the rarer chemicals that may be out there. Using the CLS, researchers are building high-resolution spectral fingerprints of methanol in all its isotopic forms that can be applied to astronomers\’ incoming data Reference: R.M. Lees, R.-J. Murphy, G. Moruzzi, A. Predoi-Cross, L.-H. Xu, D.R.T. Appadoo, B. Billinghurst, R.R.J. Golding, S. Zhao. 2009. Fourier transform spectroscopy of the CO-stretching band of O-18 methanol. Journal of Molecular Spectroscopy, 256, pp. 91-98. DOI:10.1016/j.jms.2009.02.015
Structural diagram of the UGM enzyme, derived from data collected at the CLS. This structural information is key to developing inhibitor compounds for new types of antibiotics. Image courtesy of David Sanders, University of Saskatchewan. Health: Setting sights on new antibioticsBacterial infections once thought to be on the verge of eradication have been making a comeback, like Mycobacterium tuberculosis, the bug that causes tuberculosis. The rate of antibiotics resistance is on the rise as bacteria become resistant faster than we can come up with new drugs. The problem is compounded by the fact that new antibiotics are usually developed by modifying existing ones. Thus, bacteria that become resistant to an antibiotic often also become resistant to other drugs in the same class. University of Saskatchewan researcher David Sanders is trying to buck this trend. Using the Canadian Light Source, Sanders and his team are undertaking work that may lead to the development of an entirely new class of antibiotics to which no bacteria have resistance by targeting the building blocks of the bacteria’s cell wall. Reference: S.K. Partha, K.E. van Straaten, D.A.R. Sanders, 2009. Structural Basis of Substrate Binding to UDP-galactopyranose Mutase: Crystal Structures in the Reduced and Oxidized State Complexed with UDP-galactopyranose and UDP. Journal of Molecular Biology, 394(5), pp. 864-77. DOI:10.1016/j.jmb.2009.10.013
Composite map of different types of sulphur in a microbial pod (a) obtained at the ALS, along with a comparison of spectra from the various forms of sulphur compared to reference standards from the CLS (b). K. Norlund, McMaster University. Environment: Sulphur-eating bacteria limit acid run-off and CO2Acid Mine Drainage (AMD) is caused when sulphur in mine tailings reacts with water and oxygen in the environment to produce sulphuric acid. It is a major environmental issue, with AMD a concern for lake acidification and water quality. AMD is also implicated as a climate change culprit – the sulphuric acid dissolves carbonate minerals in the underlying rock, liberating carbon dioxide in a process known as acid rock weathering. Using two beamlines at the Canadian Light Source (CLS) and a third at the Advanced Light Source (ALS), researchers from McMaster University have found that two species of bacteria isolated from a mine tailings pond in northern Ontario actually work together to limit the amount of acid produced by sharing the sulphur in the tailings as an energy source. Reference: Norlund et al. 2009. Microbial Architecture of Environmental Sulfur Processes: A Novel Syntrophic Sulfur-Metabolizing Consortia. Environmental Science and Technology 43, pp. 8781-8786.
Visible light micrograph of Barrett’s Esophagus tissue (A) and a synchrotron infrared image (B) from the CLS. The light blue area corresponds to an area rich in glycoproteins, a biomarker for Barrett’s Esophagus. Image Health: Shedding infrared light on esophageal diseaseBarrett’s Esophagus (BE) occurs when the cells that normally line the esophagus – the tube that connects our throat to our stomach – are replaced by cells that resemble those that line the intestine, leading in some cases to esophageal cancer. Luca Quaroni, a researcher at the Canadian Light Source and Dr. Alan Casson, Head of the Department of Surgery in the University of Saskatchewan’s College of Medicine used the CLS’s infrared microscope to identify Barrett’s esophagus cells from their unique chemical fingerprint. The finding was published in the Royal Society of Chemistry journal, The Analyst. Reference: L. Quaroni and A. Casson, 2009. Characterization of Barrett esophagus and esophageal adenocarcinoma by Fourier-transform infrared microscopy. The Analyst. 134, pp. 1240-1246. DOI: 10.1039/b820371d.
Artist’s interpretation of a hydrocarbon chain (centre) and smaller reactant molecules on the false-coloured surface of a Fischer-Tropsch catalyst particle. The different colours denote the distribution of different chemical forms of iron. From de Smit, et al. 2009, Angew. Chem. Int. Ed. 48: 3632-3636. Materials: Watching a catalyst at workCatalysts are used to speed up chemical reactions in many industrial processes, including storing energy in fuel cells and batteries, and processing and refining oil and gas. Using the CLS, researchers from Utrecht and Delft universities in the Netherlands have developed a powerful new technique to study how single catalyst particle works at the molecular level. The first catalyst they studied plays a key role in the synthesis of fuel from coal or biomass, instead of crude oil. The technique can also be used to study structural changes in hydrogen storage materials or examine nanoparticles inside cells. strong>Reference: de Smit et al, 2009. Nanoscale chemical imaging of the reduction behavior of a single catalyst particle. Angewandte Chemie (International Edition) 48, 20, pp. 3632-3636. DOI: 10.1002/anie.200806003.
Molecular model of the KshA enzyme from Mycobacterium tuberculosis, a new target for treating TB. Health: Getting TB off steroidsFor over 40 years, tuberculosis has been treated using a cocktail of antibiotics that must be taken for six months to a year. The long course of treatment is necessary to ensure that all of the Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, is killed off. Abandoned courses of treatment not only lead to relapses and further risk of spreading the disease, but also to the evolution of multidrug-resistant (MDR) and extensively drug resistant (XDR) strains, which now make up 20 and 2 percent of all TB cases, respectively. A discovery recently reported in the Journal of Biological Chemistry by researchers from the Canadian Light Source and the University of British Columbia sheds light both on the source of the TB bug’s resilience and a new way to treat the infection. Reference: Capyk et al. 2009, Journal of Biological Chemistry 284, pp. 9937-9946.
Molecular model of the ferritin protein from the diatom Pseudo-nitzschia multiseries, the green objects in the image background. Image courtesy of Adrian Marchetti, University of Washington. Life Science: Putting the bloom on the diatomUniversity of British Columbia researchers Michael Murphy and Angele Arrieta used the Canadian Light Source and the Stanford Synchrotron Radiation Laboratory synchrotrons to determine the molecular structure of ferritin, an iron storage protein recently discovered in a group of phytoplankton called pennate diatoms. The discovery, made by a team of scientists from the University of Washington and UBC that included Murphy and Arrieta, sheds light on how the ferritin contributes to the diatoms’ success and possible future implications for combating atmospheric carbon dioxide. The work was published in the journal Nature. Reference: Marchetti et al. 2009. Ferritin is used for iron storage in bloom-forming marine pennate diatoms. Nature 457, pp. 467-470. DOI: 10.1038/nature07539.
X-ray Photoemission Electron Microscope image of a 35 nanometer-thick stent coating after mechanical deformation. Source: Paula Horny and Stephane Turgeon, Laval University. Materials: Getting to the heart of stentsUsing the Canadian Light Source, a team of researchers from Quebec’s Laval University and Australia’s La Trobe University has discovered how to improve the nanometers-thick layer of polymer used to coat cardiac stents. The improved coatings are better able to withstand the cracking that can occur in drug-eluting stents caused by deformation during implantation and subsequent wear in the body. Reference: P. Hale, S. Turgeon, P. Horny, F. Lewis, N. Brack, G. Van Riessen, P. Pigram, D. Mantovani 2008. Langmuir 24 (15), pp. 7897—7905.
XRF map of mercury in a zebrafish head, showing the element’s concentration in the fish’s eye lenses. Courtesy of M. Korbas, University of Saskatchewan Environment: Little fish shed light on mercury poisoningThe dangers of toxic mercury exposure are well known – from the dementia of the Mad Hatter in Alice in Wonderland to recent concerns about mercury levels in the fish we eat, particularly for pregnant women and children. While scientists know that mercury is bad for us, the exact mechanism of mercury’s toxicity and how it infiltrates cells remains a mystery. Using synchrotron X-ray fluorescence (XRF) mapping at the CLS and the Stanford Synchrotron Radiation Laboratory, University of Saskatchewan researchers observed high concentrations of mercury in tissues made up of rapidly dividing cells – in this case the epithelial cells that grow the eye lens in newly hatched zebrafish. The finding has important implications for understanding the impact of mercury exposure in developing animals, including humans. Reference: M. Korbas, et al. (2008) Proceeedings of the National Academy of Sciences 105, no. 34, pp. 12108—12112.
Molecular model of Norwalk RNA polymerase, based on data collected by CMCF. Courtesy of Ken Ng, University of Calgary. Health: Revealing Norwalk Virus’ Achilles HeelOutbreaks of Norwalk virus are infamous for the havoc they can cause to people living in close quarters, from cruise ships to hospital wards. Using the CLS, an international team of researchers from the University of Calgary, University of Oviedo in Spain, Penn State, and the CLS determined the detailed structure of the enzyme used by the virus to replicate its genetic code. The information provided by the structure is a key step to designing drugs that can disrupt this replication process, stopping Norwalk and possibly its deadlier cousins, such as Hepatitis C, from spreading. Reference: Zamyatkin et al. (2008). Structural insights into mechanisms of catalysis inhibition in Norwalk Virus polymerase. Journal of Biological Chemistry 283, Number 12, pp. 7705-12. DOI: 10.1074/jbc.M709563200
Arabidopsis seedlings Environment: Increasing Crop ProductivitySelenium is an essential micronutrient for all animals but it is toxic when consumed in large amounts. In some areas of the world, including parts of Canada, the level of selenium in the soil is too high to allow grazing by livestock. In other parts, soil selenium is so low that plants do not acquire enough to satisfy the dietary requirements of people and livestock. Using the CLS, researchers are discovering how plants take-up, transport and use selenium. This information will promote the development of food crops with more selenium and thus reduce health problems caused by selenium deficiency. It could also stimulate the development of fodder crops that take-up less selenium, thereby increasing usable grazing land. References: Lydiate et al. (2008). Selenium Acquisition by Arabidopsis Plants. Canadian Light Source Activity Report 2007. In preparation.
Life Science: Regulating Nitrogen MetabolismThe ability to metabolize nitrogen is critical to all living things. The protein ‘PII’ is used by a number of organisms, including plants and bacteria. Even though the importance of PII has been known for over 40 years, how it works at the molecular level remained a mystery. Researchers from the University of Calgary determined the molecular structure, and explained how the protein works to regulate a key step in nitrogen metabolism. This information is important to understanding a biochemical process that is essential to life on Earth, and could pave the way to improved varieties of crops, new herbicides, and antibiotics. Reference: Mizuno et al. (2007). Structural basis for the regulation of N-acetlyglutamate kinase by PII in Arabadopsis thaliana. Journal of Biological Chemistry, 282, Number 49, pp. 35733-40.
Materials: Making Gold NanofingersNanotechnology involves exploiting the unique properties of materials at the scale of billionths of a meter. Scientists are working on building nanoscale components one atom at a time, using other molecules as construction tools. Researchers from the CLS and the Italian National Nanotechnology Laboratory used Canada’s synchrotron to understand the chemistry involved in creating gold nanofingers using self-acting organic molecules. Such nanofingers are the first step to creating electrical contacts a fraction of the size found on today’s microchips. Reference: Arima, Blyth, et al. Nanofingers of gold functionalized by zinc porphyrins. Small. DOI: 10.1002/smll.200700276
Photoemission Electron Microsopy images of a 35 nm-thick stent coating, before and after mechanical deformation. Source: Paula Horny and Stephane Tugeon, Laval University. Health: Spotting Problems in Coronary StentsStents are springy and tiny structures, laser-cut from metallic tubes. They are mounted on a balloon, inserted through the vessels to a narrowed section of a heart-artery, and finally deployed to reestablish blood flow, thereby warding off heart attacks. However, clinical complications occur in 30 to 45 per cent of the millions of stents implanted annually worldwide, mainly due to the re-narrowing of the arteries or loss of efficiency of the drug-charged layer in drug-coated stents. A team of researchers from Laval University is using the CLS to investigate the interface between the polymeric layer and the metallic substrate of coated stent, examine coating cracks and defects, as well as assessing the film’s chemical stability. The synchrotron was able to detect defects far below the detection limits of other high-performance techniques. This information will be mandatory for the design and evaluation of improved coatings for heart stents. Reference: Horny et al. (2008) PEEM/NEXAFS of Ultrathin Fluorocarbon Films for Coated Stents. Canadian Light Source Activity Report, 2007.
Cluster map of carbon forms Environment: Understanding Carbon in SoilUsing the CLS and the National Synchrotron Light Source in New York, Cornell University researcher Johannes Lehmann has demonstrated that, unlike previously thought, soil is a collection of identifiable biomolecules arranged on and around mineral particles. Lehmann’s team analyzed soil samples from locations around the world. They found that the arrangement of molecules and the ways they adhere to the surface of mineral particles varied at scales of a billionth of a metre. This suggests that where particular molecules are located in the soil could be critical to our understanding of how soil absorbs, stores and releases carbon, in response to changes in ecology and climate. Reference: Lehmann et al. (2008). Spatial complexity of soil organic matter forms at nanometer scales. Nature Geoscience, 1, pp. 238-42. DOI: 10.1038/ngeo155. Reference: Lehmann et al. (2008). Spatial complexity of soil organic matter forms at nanometer scales. Nature Geoscience, 1, pp. 238-42. DOI: 10.1038/ngeo155.
A high resolution infrared map of a rod cell (right) indicates protein distribution in a rod cell (photomicrograph at left). Images courtesy of Luca Quaroni, CLS. Life Science: Looking at Proteins inside Live CellsUnderstanding the relationship between a protein’s molecular structure and its function is a cornerstone of modern biochemistry, medicine, and biotechnology. CLS staff scientist Luca Quaroni is using the synchrotron’s infrared microscope to study the structure-function relationship of proteins inside living cells, like the protein rhodopsin, found in the retina. By using the synchrotron’s super-bright infrared light, Quaroni can map where proteins are found, and determine their shape, and how they align to the rest of the cell. This discovery could lead to new understandings of how the molecular properties of proteins affect the overall function of a cell.
Materials: Building a Better NanotubeCarbon nanotubes—tubes made up of rolled sheets of carbon atoms — are being developed for a variety of applications, including electronic devices and sensors for medical applications. Mass-producing nanotubes that are free of impurities or random defects is a major challenge. Improving the manufacturing process depends on the ability to detect defects in individual nanotubes. An international team of scientists from McMaster University, Belgium’s University of Namur, and the CLS, first discovered the polarization properties of nanotubes, and demonstrated that defects in individual nanotubes can be detected by using polarized synchrotron light and a state-of-the-art X-ray microscope at the CLS. The CLS soft X-ray spectromicroscopy beam line can fully control the polarization of the X-rays and thus is the best system in the world to characterize individual nanotubes and thereby help perfect how they are made. Reference: Najafi, et al. (submitted) Small; Najafi et al (2008). Studies of the Linear Dichroism of Individual Carbon Nanotubes with STXM at the C 1s Edge. Canadian Light Source Activity Report 2007.
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