Snaphot of molecular mechanism at work in lethal virus

X-ray crystallography at the Australian Synchrotron contributed to major research findings.

Data collected on the macromolecular crystallography beamlines at the Australian Synchrotron has contributed to major research findings on two deadly viruses, Hendra and Nipah, found in Australia, Asia and Africa. The viruses can be transmitted to humans not directly by the bat which is the natural carrier but by an infected animal like horses or pigs.

Beamline scientist, Dr David Aragao (pictured above), a co-author on the paper in Nature Communications, said that obtaining a clear motion picture of key biological process at the molecular level of viruses is often not available with current biomedical techniques.
“However, using X-ray crystallography from data collected on both MX1 and MX2 beamlines at the Australian Synchrotron, we were able to obtain  8  ‘photograph-like’ snapshots of the molecular process that allows the Hendra and Nipah virus to replicate.“

Two authors of the paper, PhD students Kate Smith and Sofiya Tsimbalyuk, who are co-supervised by Aragao and his collaborator Professor of Biochemistry Jade Forwood of the Graham Centre for Agricultural Innovation Charles Sturt University, used the Synchrotron extensively collecting multiple data sets that required extensive refinements over two years to isolate the mechanism of interest.

>Read more on the Australian Synchrotron website

Image: Beamline scientist, Dr David Aragao.

Using uranium to create order from disorder

The first demonstration of reversible symmetry lowering phase transformation with heating.

ANSTO’s unique landmark infrastructure has been used to study uranium, the keystone to the nuclear fuel cycle. The advanced instruments at the Australian Synchrotron and the Australian Centre for Neutron Scattering  have not only provided high resolution and precision, but also allowed in situ experiments to be carried out under extreme sample environments such as high temperature, high pressure and controlled gas atmosphere.

As part of his joint PhD studies at the University of Sydney and ANSTO, Gabriel Murphy has been investigating the condensed matter chemistry of a crystalline material, oxygen-deficient strontium uranium oxide, SrUO4-x, which exhibits the unusual property of having ordered defects at high temperatures.

“Strontium uranium oxide is potentially relevant to spent nuclear fuel partitioning and reprocessing,” said Dr Zhaoming Zhang, Gabriel’s ANSTO supervisor and a co-author on the paper with Prof Brendan Kennedy of the University of Sydney that was published recently in Inorganic Chemistry.
Uranium oxides can access several valence states, from tetravalent— encountered commonly in UO2 nuclear fuels, to pentavalent and hexavalent—encountered in both fuel precursor preparation and fuel reprocessing conditions.
Pertinent to the latter scenario, the common fission daughter Sr-90 may react with oxidised uranium to form ternary phases such as SrUO4.

>Read more on the Australian Synchrotron website

Image: Dr Zhaoming Zhang and Gabriel Murphy.

Advanced imaging technique used to study triggers of tree mortality

Researchers are using advanced imaging technologies similar to those used in hospitals, including micro-computed tomography on the Imaging and Medical beamline (IMBL) at the Australian Synchrotron, to determine how vulnerable our trees are to drought and heatwaves.
A new scientific review published In Nature outlines progress towards understanding the likely risks from droughts and heatwaves that combine to kill millions of trees around the world with spectacular effects on the environment.

Recent drought and heatwave conditions in northern Australia have killed more than 7000ha of mangrove forests, leaving these essential ecosystems stark, grey skeletons of trees. In California, the prolonged drought period has killed more than 100 million trees that increase the intensity of wildfires and impact on the region’s beauty, tourism and environmental health.
Dead trees, of course, cannot store carbon out of the air and the enormous numbers of dead trees release large quantities of stored carbon back into the air as they are burned or decay, further amplifying the effects of rising carbon dioxide.

>Read more on the Australian Synchrotron website

Image: IMBL robot positions the tree for imaging.

New class of single atoms catalysts for carbon nanotubes

They exhibit outstanding electrochemical reduction of CO2 to CO.

Experiments using X-rays on two beamlines at the Australian Synchrotron have helped characterise a new class of single atom catalysts (SACs) supported on carbon nanotubes that exhibit outstanding electrochemical reduction of CO2 to CO. A weight loading of 20 wt% for the new class, nickel single atom nitrogen doped carbon nanotubes (NiSA-N-CNTs), is believed to be the highest metal loading for SACs reported to date.

Single atoms of nickel, cobalt and iron were supported on nitrogen doped carbon nanotubes via a one-pot pyrolysis method and compared in the study.

A large international collaboration, led by Prof San Ping Jiang, Deputy Director of the Fuels and Energy Technology Institute at the Curtin University of Technology and associates from the Department of Chemical Engineering, have developed a new synthesis and development process for nitrogen-doped carbon nanotubes with a nickel ligand that demonstrate high catalytic activity.

The study was published in Advanced Materials and featured on the inside cover of the publication.

Dr Bernt Johannessen, instrument scientist on the X-ray absorption spectroscopy (XAS) beamline at the Australian Synchrotron was a co-author on the paper, which also included lead investigators from Curtin University of Technology and collaborators at the University of Western Australia, Institute of Metal Research (China), Oak Ridge National Laboratory (US), University of the Sunshine Coast, University of Queensland, Tsinghua University (China) and King Abdulaziz University (Saudi Arabia). Technical support and advice on the soft X-ray spectroscopy experiments was provided by Australian Synchrotron instrument scientist Dr Bruce Cowie.

>Read more on the Australian Synchrotron website

Image: extract of the cover of Advanced Materials.

Insights into the development of more effective anti-tumour drug

Natural killer cells are powerful weapons our body’s immune systems count on to fight infection and combat diseases like cancer, multiple sclerosis, and lupus. Finding ways to spark these potent cells into action could lead to more effective cancer treatments and vaccines.

While several chemical compounds have shown promise stimulating a type of natural killer cells, invariant natural killer T cells (iNKT) cells in animal models, their ability to activate human iNKT cells has been limited.

Now, an international team of top immunologists, structural biologists, and chemists published in Cell Chemical Biology the creation of a new compound that appears to have the properties researchers have been looking for. The research was co-led by Monash Biomedicine Discovery Institute’s (BDI) Dr Jérôme Le Nours, University of Connecticut’s Professor Amy Howell and Albert Einstein College of Medicine’s Dr Steve Porcelli. Dr Le Nours used the Micro Crystallography beamline (MX2) at the Australian Synchrotron as part of the study.

The compound – a modified version of an earlier synthesized ligand – is highly effective in activating human iNKT cells. It is also selective – encouraging iNKT cells to release a specific set of proteins known as Th1 cytokines, which stimulate anti-tumour immunity.

>Read more on the Australian Synchrotron website

Image: 3D structure of proteins behind interaction of new drug that stimulates immune response to cancer cells. (Entire image here)

Success in clinical trials driving a shift in the treatment of blood cancers

The Australian Synchrotron is proud to be growing Australia’s capacity for innovative drug development, facilitating the advance of world-class disease and drug research through to local drug trials. Recent success in clinical trials of Venetoclax, the chronic lymphocytic leukaemia (CLL) drug developed by researchers from the Walter and Eliza Hall Institute and two international pharmaceutical companies is driving a major shift in the treatment of a range of blood cancers, according to a media information from the Peter MacCallum Cancer Centre.

>Read more on the Australian Synchrotron website

 

Combining X-ray techniques for powerful insights into hyperaccumulator plants

The complementary power of combining multiple X-ray techniques to understand the unusual properties of hyperaccumulator plants has been highlighted in a new cover article just published in New Phytologist.

X-ray fluorescence microscopy (XFM) at the Australian Synchrotron has been used by a consortium of international researchers led by Dr Antony van der Ent of the Centre for Mined Land Rehabilitation at The University of Queensland, in association with A/Prof Peter Kopittke of the School of Agriculture and Food Science also at The University of Queensland.

The XFM technique generates elemental maps showing where elements of interest are found within plant tissue, seedlings or individual cells.
Visually striking images (obtained at the XFM beamline) show various hyperaccumulator plants, on the cover of the April issue of New Phytologist. In the images each element is depicted in a different colour, making up a red-green-blue (RGB) image.

“Hyperaccumulator plants have the unusual ability to accumulate extreme concentrations of metals and metalloids in their living tissues,” said van der Ent.
“Hyperaccumulators are of scientific interest because whilst metals are normally toxic to plants even at low concentrations, these plants are able to accumulate large concentrations without any toxic effects,” he added

>Read more on the Autralian Synchrotron website

Image: X‐ray Fluorescence (XRF) elemental maps of hyperaccumulator plants. The tricolour composite images show (left to right) root cross‐section of Senecio coronatus (red, iron; green, nickel; blue, potassium); and seedlings of Alyssum murale (red, calcium; green, nickel; blue, Compton scatter).
Credit: A. van der Ent. 

Modifications to novel non-fullerene small molecule acceptor in organic thin film

… for solar cells demonstrates improved power conversion efficiency.

Scientists from the Imperial College London, Monash University, CSIRO, and King Abdullah University of Science and Technology have reported an organic thin film for solar cells with a non-fullerene small molecule acceptor that achieved a power conversion efficiency of just over 13 per cent.

By replacing phenylalkyl side chains in indacenodithieno[3,2-b]thiophene-based non-fullerene acceptor (ITIC) with simple linear chains to form C8-ITIC, they improved the photovoltaic performance of the material.

C8-ITIC was blended with a fluorinated analog of the donor polymer PBDB-T to form bulk-heterojunction thin films.

The research was recently published in Advanced Materials.

Dr Xuechen Jiao of McNeill Research Group at Monash University carried out grazing incidence wide angle X-ray scattering (GIWAXS) measurements at the Australian Synchrotron to gain morphological information on pure and blended thin films.

“By changing the chemical structure of the organic compound, a promising boost in efficiency was successfully achieved in an already high-performing organic solar cells” said Jiao.

>Read more on the Australian Synchrotron website

 

Technique provides insights into historic maritime artefact

Recently an advanced X-ray imaging technique was used on a historic pewter plate linked to the early exploration of Australia by the Dutch in the 17th century. X-ray fluorescence (XRF) has proven to be a highly useful analytical tool for the study of cultural objects, such as works of art and artefacts.

“The non-destructive analysis can provide information about how the objects were made, their composition and insight for conservation strategies,” said XRF beamline scientist Dr Daryl Howard.
“The fast detector on the instrument and its high sensitivity allows us to keep the exposure to radiation to a minimum, which is important for rare and valuable objects. “

In December last year, a small group from the Rijksmuseum in Amsterdam and the Queen Victoria Museum and Art Gallery (QVMAG) in Tasmania brought the Hartog Plate to the Synchrotron for scanning.

>Read more on the Australian Synchrotron website

Image: (extract) X-ray fluorescence scan image showing elemental distribution of bismuth (red) lead (green) and germanium (blue). Entire picture here.

Hijacker parasite blocked from infiltrating blood

A major international collaboration led by Melbourne researchers has discovered that the world’s most widespread malaria parasite infects humans by hijacking a protein the body cannot live without.

The researchers were then able to successfully develop antibodies that disabled the parasite from carrying out this activity.
The study, led by the Walter and Eliza Hall Institute’s Associate Professor Wai-Hong Tham and Dr Jakub Gruszczyk, found that the deadly malaria parasite Plasmodium vivax (P. vivax) causes infection through latching onto the human transferrin receptor protein, which is crucial for iron delivery into the body’s young red blood cells.

Published today in Science, the discovery has solved a mystery that researchers have been grappling with for decades.
The MX and SAXS beamline staff at the Australian Synchrotron assisted with data collection.

Associate Professor Tham, who is also a HHMI-Wellcome International Research Scholar, said the collective efforts of teams from Australia, New Zealand, Singapore, Thailand, United Kingdom, United States, Brazil and Germany had brought the world closer to a potential effective vaccine against P.vivax malaria.

>Read more on the Australian Synchrotron website

 

Combined imaging approach characterises plaques associated with Alzheimer’s disease

Australian Synchrotron X-ray and infrared imaging techniques have been used in a powerful combined approach to characterise the composition of amyloid plaques that are associated with Alzheimer’s disease.

Alzheimer’s disease is major international health problem that accounts for 50-75 per cent of all cases of dementia in Australia. More than 400,000 Australians are living with dementia and it is the second leading cause of death.

Amyloid plaques are complex protein fragments which accumulate between nerve cells in the brain and may destroy connections between them, and are hallmarks of Alzheimer’s disease.

“However, it is still not known if the plaques cause Alzheimer’s or whether the Alzheimer’s causes their formation, which is why we need to improve our understanding of protein structures within plaques, and the molecular and elemental composition of tissue surrounding the plaques“ said Dr Mark Hackett of Curtin University, who led the research.

The study was published earlier in the year in Biochemistry.

As very few methods provide sufficient chemical information to study the composition and distribution of the plaques in excised tissue, the investigators decided to combine Synchrotron spectroscopic techniques with additional imaging methods, Raman spectroscopy and fluorescence microscopy.

>Read more on the Australian synchrotron website

Image Caption: Histology, FTIR, XFM, and tissue autofluorescence imaging of Aβ-plaques

How ANSTO can assist research community?

Approximately 190 participants attended the first combined ANSTO User Meeting

The event brought representatives of research communities together who have accessed various ANSTO infrastructure platforms.

“It was an opportunity to look at the scientific challenges and questions that are being addressed and consider how multiple techniques and experimental methods can be applied to answering those questions,” said co-convenor Dr Miles Apperley, Head of Research Infrastructure, who spoke at the opening.

ANSTO has nine research infrastructure platforms in total, including the Australian Centre for Neutron Scattering and the Australian Synchrotron that provide user-focused open-access support to researchers from Australia and across the globe.

Plenary speakers included leading Australian and International researchers.

2017 ANSTO, Australian Synchrotron Stephen Wilkins Medal awarded

Leonie van ‘t Hag has been awarded the Australian Synchrotron S. Wilkins Medal for her PhD thesis

The award recognises her research to improve the method to crystallise proteins and peptides in order to study their structure, using a technique called crystallography. “Leonie’s insights into crystallisation processes could significantly help the development of treatments for a variety of illnesses,” said Australian Synchrotron Director, Professor Andrew Peele.

Most solid material in the world is made of crystalline structures. Crystals are made up of rows and rows of atoms or molecules stacked up like boxes in a warehouse, in different arrangements.

The science of determining these atomic or molecular structures from crystalline materials is called crystallography.

3D structure of a molecular scaffold with role in cancer

The research team is looking at ways of targeting parts of the scaffold molecule critical for its function

Melbourne researchers have used the Australian Synchrotron to produce the first three-dimensional structure of a molecular scaffold, known to play a critical role in the development and spread of aggressive breast, colon and pancreatic cancer.
Armed with the structure, the research team is looking at ways of targeting parts of the scaffold molecule critical for its function. They hope the research will lead to novel strategies to target cancer.

The research was the result of a long-standing collaboration between Walter and Eliza Hall Institute (WEHI) researchers Dr Onisha Patel and Dr Isabelle Lucet and Monash University Biomedical Research Institute researcher Professor Roger Daly.

Dr Santosh Panjikar, a macromolecular crystallographer at the Australian Synchrotron and Dr Michael Griffin from Bio21 Institute at the University of Melbourne made important contributions to the study, which was published in the journal Nature Communications.