Cross-Tasman collaboration between Australian and New Zealand researchers has shed light on a protein involved in diseases such as Parkinson’s disease, gastric cancer and melanoma.
Using the Australian Synchrotron, a team of researchers led by Dr Peter Mace from the University of Otago, in collaboration with Australian scientists investigated a protein called Apoptosis signal-regulating kinase 1 (ASK 1) with the results published today in leading international journal PNAS.
Dr Mace says the protein plays an important role in controlling how a cell responds to cell damage, and can push the cell towards a process of programmed cell death for the good of the body, if damage to a cell is too great.
“We now know a lot more about how ASK1 gets turned on and off – this is important because in diseases such as Parkinson’s, stomach cancer and melanoma, there can be either too much or too little ASK1 activity,” he said.
The ASK1 protein gets its name from an ancient Greek word meaning “falling off” – apoptosis – and is used to describe the process of programmed dying of cells – of the body actively killing them – rather than their loss by injury.
Researchers found that ASK1 has unexpected parts to its structure, that help control how the protein is turned on, and that an entire family of ASK kinases share these features.
Dr Mace says that the new findings add to our understanding of how cells can trigger specific responses to different threats or damage encountered, such as oxidants, which damage the body’s tissues by causing inflammation.
He adds that kinases are excellent targets for developing new drugs because they have a “pocket” in their structure that such compounds can bind to, but to develop better drugs we need to understand far more about how they are controlled. This is the goal of several projects in his lab, he says.
The research team determined ASK1’s molecular structure through crystallography studies – using the Synchrotron to see exactly what it is made up of – and performed other biochemical experiments to better understand the protein.
Dr Tom Caradoc-Davies, (below) Principal Scientist of the Macromolecular Crystallography and Micro Crystallography beamlines at the Australian Synchrotron, helped to collect data critical to the project.
Dr Tom Caradoc-Davies on the MX beamline at the Australian Synchrotron
“Using the Synchrotron’s MX Beamlines, we collected data from difficult samples, to help solve questions the research team had about the structure of the protein,” Dr Caradoc-Davies said.
“This is a great example of how regular access to the Synchrotron’s facilities can help move a project along more rapidly than otherwise would be the case, where it could take many years more for a team to find an answer, or they may not be able to find one at all.”
The study is a collaboration between Otago researchers and scientists at the Walter and Eliza Hall Institute (WEHI) in Melbourne, and at the Australian Synchrotron.
Access to this ANSTO landmark research infrastructure was enabled by the New Zealand Synchrotron Group, which is coordinated by the Royal Society of New Zealand and supported by all New Zealand universities in partnership with the Australian and New Zealand Governments.
The Australian Synchrotron is crucial to many other research projects from Otago and throughout New Zealand.
The study was supported by a Royal Society of New Zealand Rutherford Discovery Fellowship and grants from the University of Otago, the Victorian State Government and the National Health and Medical Research Council.
It has been a year like no other at the Australian Synchrotron; 2016 saw the securing of $520 million over ten years in operational funding in December 2015 and the transfer of ownership to the Australian Nuclear Science and Technology Organisation (ANSTO) in July 2016, while hosting 5,700 visits by researchers from across Australia, New Zealand and around the world.
In a year that also saw celebrations of ten years since ‘First Light’, the landmark research infrastructure continued to empower researchers and industry to problem solve and innovate, supporting the delivery of real life benefits including durable, rapidly-printable electronics; next-generation batteries that run on sea water; non-invasive brain electrodes to help overcome paralysis; and ‘stainless magnesium’ that could herald a transport revolution.
Looking forward to a new era as part of ANSTO’s world-class suite of landmark research infrastructure, the future looks even brighter. In 2017 and beyond additional capacity and new capability will be realised through nationwide partnerships under the BR-GHT expansion program, enabling the rapid progression of research by harnessing the power of eight new synchrotron techniques.
Left: Dr Wenchao Huang with his PhD supervisor, Associate Professor Chris McNeill from the Faculty of Materials Science and Engineering at Monash University; right: an organic solar cell; inset: the Australian Synchrotron Stephen Wilkins Thesis Award medal.
A young Melbourne researcher has helped lay the groundwork for an environmentally-friendly electronics revolution, defining the complex chemistry that could see affordable, translucent, printable solar panels moulded and shaped to adorn home windows and office towers.
Dr Wenchao Huang today received the 2016 Australian Synchrotron Stephen Wilkins Thesis Medal for his research at Monash University into organic photovoltaic (OPV) devices, exploring how critical microstructural features evolve during the preparation of cutting-edge, clear and pliable solar panels, which are tipped to surpass older, silicon-based panels in value and performance over the next decade.
Associate Professor Chris McNeill from the Faculty of Materials Science and Engineering at Monash University says Dr Huang’s research balanced the activity of two key solar panel components.
‘In the active layer of a polymer solar cell you have the polymer donor – which absorbs sunlight and generates electron-hole pairs – and the fullerene acceptor, which transports electrons to electrodes.
‘Under different circumstances, the polymer can become crystallised, which makes charge transport and light absorption more efficient, but reduces the probability that electrons will be successfully transferred to the fullerene, which has a negative effect on power conversion efficiency; experimenting with heat treatment and additive solvents, Wenchao used the Australian Synchrotron’s Soft X-Ray Spectroscopy (SXR) beamline to find a workable balance that we believe will make OPV’s more commercially viable.’
Dr Huang, who has since winged his way to new opportunities in the United States at the University of California, Los Angeles, says the key to bringing next-generation solar cells into our homes and workplaces is maximising the power conversion efficiency.
‘Silicon has had a huge head start – coming into play in the 1950s while organic solar cells appeared in the mid-1990s – yet commercialised single-crystal silicon solar cells convert around 18-20 per cent of energy from the sun into power, next to 12 per cent for organic.
‘We anticipate it will be only years, not decades, until organic takes the lead, costing around half or one third to produce.’
Associate Professor McNeill says the team at the Australian Synchrotron provided crucial molecular analysis as broader techniques of the ongoing research were developed, which could impact Australia’s green energy future.
‘We believe the upscaling of OPV’s will enable faster development of next-generation solar panels and electronics that are flexible, malleable and more affordable, beyond the limitations of bulky silicon-based electronics.
‘The ability to incorporate solar panels into clear windows on houses, skyscrapers and stadiums is a very attractive prospect as Australia works towards a sustainable energy mix that maintains output and reliability while lowering carbon emissions.’
Professor Andrew Peele, Director of the Australian Synchrotron and ANSTO Victoria, says through research opening up new pathways for innovation that deliver real life benefits, Dr Huang is a worthy recipient of the medal, which is named in honour of synchrotron pioneer Stephen Wilkins.
‘Science is about turning big ideas into innovations that change our world, and Wenchao has embodied this spirit by tackling a complex technical issue using synchrotron science in a way that could revolutionise affordable, renewable energy.
‘The thesis medal honours Stephen Wilkins’ creativity and his devotion to nurturing the next generation of scientists, and we wish Wenchao well as he builds his career in the United States.’
The Australian Synchrotron Stephen Wilkins Thesis Medal is awarded annually to the PhD student at an Australian or New Zealand university judged to have completed the most outstanding thesis of the past two years, and whose work was undertaken at and acknowledges the Australian Synchrotron or the Australian National Beamline Facility.
It was a fittingly sunny afternoon to discuss the power of light when around 130 people, from confessed computing experts to young scientists of the future, gathered in Perth last week to learn how big data and big ideas are translated into real life benefits by experts at the Australian Synchrotron and across the Australian Nuclear Science and Technology Organisation (ANSTO)’s suite of world-class landmark research infrastructure.
At the ‘Big data + big ideas = real-life benefits’ lecture, Australian Synchrotron Director Professor Andrew Peele showed dazzling rich-colour images that shed insight into the mind-bending computing behind the real-life benefits delivered through the Australian Synchrotron: from peeling back the surface of priceless artworks to de-clogging inkjet printers, and from enriching the nutrients in essential foods to pharmaceutical breakthrough that are changing the lives of people with cancers and coeliac and Alzheimer’s diseases.
Embarking on a ‘deep dive’ into the mechanics of big data, Dr Andreas Moll, Senior Scientific Software Engineer, took the audience through the creation of a one gigapixel image, from data collection and processing to stitching and reconstruction. Incredibly, Dr Moll told guests that technical upgrades to key equipment on one of the facility’s ten beamlines will see data acquisition that currently takes 15 minutes, reduced to only 18 seconds accelerating health and medical research.
In a further nod to the future, Professor Peele explained how advances in synchrotron technology are rapidly outpacing increases in the speed of conventional computing devices, paving the way for new investment at the landmark research facility that will massively expand the ability of Australian Synchrotron scientists to translate its torrents of data into improvements in the way we work, eat and live, through partnership with academic researchers and industry clients from across Australia, New Zealand and around the world.
Hosted by Dr Erica Smyth, Deputy Chair of ANSTO and Chair of the WA Mega Data Cluster and emceed by Dr Miles Apperley, Head of Research Infrastructure at ANSTO, the lecture left a buzz in the air at the Harry Perkins Institute of Medical Research with one guest describing the display of technical know-how as ‘brain-blasting’.
Associate Professor Natalie Sims, leader of the research team, with Christina Vrahnas, first author on the Bone journal paper.
Melbourne researchers have used the Australian Synchrotron to reveal how bone made in people taking hormone treatment for advanced osteoporosis is likely to be stronger and more durable than previously thought, offering new insights into skeletal diseases and ways of predicting who may be at risk of fractures and breaks.
The experimental technique, developed by researchers from St Vincent’s Institute of Medical Research (SVI) in Melbourne and revealed online in Bone ahead of appearing in the December edition, uses infrared synchrotron light to monitor tiny sections of newly-formed bone at different times, in conditions mimicking the human body, influenced by parathyroid hormone treatment (PTH) or teriparatide.
SVI’s Associate Professor Natalie Sims, leader of the research team, says PTH is one of very few recommended second-line treatments for people with serious bone diseases, including osteoporosis.
‘PTH stimulates the production of new bone when bone fragility persists after first-line treatments fail, but previous studies suggested this replacement bone was not as strong as existing bone which, in turn, was thought to be behind ongoing fractures and breaks in people who had daily PTH injections.
‘Not only has our analysis shown replacement bone has exactly the composition and structure that it should, our investigative technique opens the door to previously impossible bone examination, which could shed new light on all skeletal diseases including osteogenesis imperfecta and osteomalacia.’
Associate Professor Sims says using the Australian Synchrotron, landmark research infrastructure of the Australian Nuclear Science and Technology Organisation (ANSTO), gave the research team new appreciation of how bones regrow, in unprecedented detail and accuracy.
‘When bone forms, collagen is laid down in a matrix, in which calcium builds over time in a process called mineralisation – it is crucial that we can probe deep into the bone matrix because on the surface, just like wood, both weak and strong bone can look exactly the same.
‘Moreover, the ability to analyse tiny bone sections only 15 microns across – about the size of two blood cells – meant we could go deeper and deeper into older and older bone in tiny increments, to identify structural differences: clues as to which bone was truly strong and which was truly weak.’
Professor Peter Ebeling AO, Head, Department of Medicine, Monash University at Monash Health says the new avenue of bone research could lead to improved diagnostic tests and approaches to predicting breaks and fractures.
‘Current bone density tests are quite good at telling us who is at most risk of fractures but, in many cases, they do not tell the full story.
‘By looking at tiny samples, as opposed to centimetres-long bone sections, it will be tremendous if this research can help inform a more precise and useful approach, as well as assisting with testing the efficacy of future, improved bone disease drugs that are able to build new bone.’
- 'Useful break in bone study', Herald Sun, Friday 28 October 2016
Professor Andrew Peele, Director of the Australian Synchrotron and Dr Sarawut Sujitjorn, Director of the Synchrotron Light Research Institute of Thailand, at Clayton in Victoria.
A new era of regional scientific cooperation begun this week with the signing of a Memorandum of Understanding (MoU) in Clayton between the Australian Synchrotron and the Synchrotron Light Research Institute (SLRI) of Thailand.
Over a two-day visit, which involved a tour of the Imaging and Medical Beamline (IMBL), roundtable discussions and an official dinner, executive board members of SLRI learned about the history, operations and future of the Australian Synchrotron, which will inform the development of the 1.2 GeV Siam Photon Laboratory (SPL), the first synchrotron facility in Thailand.
Discussions covered approaches to safety and risk, plans for expansion and business development and the broad range of supporting services ensuring the landmark ANSTO research infrastructure continues to go from strength to strength.
Future cooperation enabled by the MoU could involve the sharing of brainpower and expertise, as the Thai delegation expressed a desire to cooperate on a staff exchange program with the Australian Synchrotron.
Experts estimate less than 30 Orange-bellied Parrots remain in the wild. Researchers from Charles Sturt University have partnered with scientists from the Australian Synchrotron to reconstruct the outer shell of a beak and feather disease (BFD) virus cell (inset), which is threatening four species of endangered Australian parrot.
Australian researchers have unravelled the molecular makeup of a virus threatening some of the world’s most endangered species, paving the way for the potential development of a vaccine to save dwindling populations of the Australian birds.
The research, led by Charles Sturt University (CSU) scientists and published in the prestigious international journal Nature Communications overnight, revealed the structure of the smallest self-replicating virus behind the beak and feather disease (BFD).
The virus causes a debilitating disease affecting four rare species of native parrot, including the Western ground and Orange-bellied Parrots (pictured, above), of which less than 50 remain in the wild.
CSU Professor in Biochemistry Jade Forwood said, ‘We now have a unique way of thinking about the virus and how it self-assembles. We know at the atomic level, the structure of the virus and how it fits together.’
CSU Professor in Veterinary Pathobiology Shane Raidal said, ‘The finding is significant because, by confirming how the viral structure forms, we can begin to develop a vaccine to interrupt these processes.’
The BFD virus programs only two proteins to drive its replication and spread: one to assist the reproduction of the viral DNA, and one to construct the outer shell of the virus. This shell is built from 60 individual capsid proteins that self-assemble and fit together in a highly specific and ordered arrangement around the viral DNA.
The outcomes of this research provide the atomic coordinates of approximately 200,000 atoms which make up the virus, and insights into how the viral DNA can bind to the shell, ensuring the protection and delivery of the viral DNA.
At the Australian Synchrotron in Melbourne, landmark research infrastructure of the Australian Nuclear Science and Technology Organisation (ANSTO), the Micro Crystallography (MX2) beamline produced X-rays more than a million times brighter than the sun to create intricate diffraction patterns as light bounced off microscopic crystals of the viral capsid proteins. This allowed the researchers to identify the locations of the individual atoms and broader structure of the viral shells in stunning 3D detail.
The research team, involving scientists from CSU, Monash University, the Australian Synchrotron, and Spain’s National Microbiology Centre and the Autonomous University of Madrid, have been working on the project since 2009.
Along with the loss of habitat and feral predators, the BFD virus is one of the main threats to the affected parrots, which also include the Norfolk Parakeet (Norfolk Island) and the Swift Parrot (eastern and southern states). Infected birds face starvation and death as their feathers moult and their beaks soften.
Professor Raidal said, ‘The disease has caused significant problems, in particular, for the Orange-bellied Parrot since 2006 when it reappeared in the captive recovery program.
‘The Parrot is a small and vulnerable migratory bird which breeds only on Tasmania’s south-west coast, flying north to spend the winter in coastal Victoria and South Australia, so we look forward to building on this work to find new approaches to restoring their numbers in the wild.’
Mr Barry Baker, Chair of the national Orange-bellied Parrot Recovery Team said it is important new and innovative fields of science work across conservation projects to protect Australia’s at-risk fauna.
‘BFDV is an awful disease, especially in small, short-lived species like Orange-bellied Parrots – young birds with the virus stand little chance of survival in the wild, and affected captive birds are often compromised, as the virus can affect the bird’s ability to fight off other health issues.
‘Although recent Orange-bellied Parrot recovery efforts have proven effective, in 2014 the wild population suffered from a spillover of BFDV (from another wild species) and we believe there are currently less than 30 birds out there – another outbreak of the disease in the wild would be a disaster, so the ability to vaccinate would be a leap forward in parrot conservation, also benefitting captive populations and our ability to release to the wild.’
- 'New weapon against virus killing Australia's endangered parrots', Australian Geographic, Thursday 6 October 2016
- 'Aus researchers’ bird virus breakthrough' on Nine News online, Wednesday 5 October 2016
Whether you’re a synchrotron star keen for the latest technical updates or a student ready to sell your science in the Poster Slam, User Meeting 2016 has something for everyone. Showcasing the best research undertaken at the Australian Synchrotron and featuring local and international plenary speakers, User Meeting 2016 will provide updates on cutting-edge technique and application developments over a two-day program featuring themes and sessions on advanced materials, biological systems, structural biology, earth and environment, therapies, surfaces, industry and imaging.
We’re open for registrations and now calling for abstract submissions.
For more information, visit: Australian Synchrotron User Meeting 2016
Lloyd Rees Memorial Lecture by Professor Keith Nugent
Thursday 6 October, 2016 at 2.30 pm at the Wark Theatre at CSIRO Manufacturing
Sources of the energetic form of light known as X-rays are developing at an enormous rate. Indeed, by one measure, they are improving at a rate that exceeds computing’s famous Moore’s Law.
The rapid improvement of synchrotron sources has driven a very significant part of this growth over the last few decades, but the already dizzying rate of development has recently been accelerated by the construction of X-Ray Free Electron Lasers (XFELS), with the first beginning operation in the USA in 2011. XFELS are now either operating or under construction in a number of countries around the world.
XFELS are based on linear accelerator technology and are able to produce pulses of X-Rays that can be up to ten orders of magnitude brighter than the pulses from modern synchrotrons. This extraordinary growth in capability is certain to unlock new scientific insights and new technologies. In this talk, Professor Nugent will describe the physics underpinning X-Ray Free Electron Lasers. He will go on to outline some of the scientific drivers behind the significant global investment in X-Ray lasers, with the most important being the possibility of imaging a single biomolecule. He will describe his progress towards these scientific goals.
Light refreshments available after the Lecture.
About the speaker
Professor Keith Nugent FAA is internationally recognised for his outstanding contributions to Chemical Physics. As Director of the ARC Centre of Excellence for Coherent X-Ray Science from 2005 to 2013 he has driven the development of coherent X-Ray diffraction methods for imaging biological structures. His other important contribution to Chemical Physics focuses on the complete recovery of phase from intensity and the applications of this to imaging
We are all on an inescapable journey through the universe with our nearest star: our sun. If our kind manages to survive for hundreds or thousands of millions of years, we are in for one a hell of a ride.
On Thursday 25 August, join researcher in fundamental physics from the DAFNE collider in Frascati Italy, Dr Catalina Curceanu, on an imaginary journey through space and time: Riding on a star – this year’s Victorian Women in Physics lecture.
- Discover how stars work
- Find out what keeps stars alive and what happens when they die
- See how a star can become an impressive supernova and give birth to a neutron star
- Wonder the forces that bring about black holes …
- and ponder an important question for our distant descendants: How will our own meet its end?
The Victorian Women in Physics lecture celebrates the contribution of women to advances in physics; this year it is hosted by La Trobe Institute for Molecular Sciences.
For more information visit the Australian Institute of Physics.
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