Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female mosquitoes. About 3.2 billion people – almost half of the world’s population – are at risk of malaria.
Researchers from The University of Sydney in collaboration with the Australian Synchrotron, the Australian Nuclear Science and Technology Organisation (ANSTO) and researchers in the United States, have revealed how a dangerous form of malaria can lead to brain damage and death, developing a new multi-modal imaging approach that could also shed light on neurodegenerative diseases including Parkinson’s and Alzheimer’s.
In the research, funded by the Australian Research Council and published overnight in Science Advances, the team used a suite of imaging techniques to solve decades-old controversies on how ‘friendly fire’ of the immune system causes deadly cerebral malaria, a disease mostly affecting children under five in Africa and adults in South East Asia, paving the way for new anti-inflammatory and anti-oxidant treatments.
Dr Mark Hackett from The University of Sydney, says the research produced complementary information from five forms of imaging – including the spread of metals, density of haemoglobins and distribution of other biomolecules – providing conclusive evidence of how malaria-infected red blood cells can induce brain damage.
‘To avoid being cleansed from the body by the spleen, malaria-infected red blood cells are forced by the parasite to display sticky proteins on their surface, allowing them to anchor to the walls of small blood vessels elsewhere in the body; when this occurs in the brain it can result in cerebral malaria.
‘Using cutting-edge imaging techniques we showed, in cerebral malaria, the biochemical damage caused when the immune system attacks to kill the infected, anchored blood cells, breaches the highly sensitive blood-brain barrier, allowing the mingling of blood and inflammatory molecules in brain tissue, leading to its destruction.’
Dr Hackett says the combined imaging approach drew on the best attributes of microscopy resources at the Australian partner organisations, and high spatial resolution X-Ray fluorescence microscopy at Argonne National Laboratory in the United States, to gather information without chemically interfering with brain tissue samples, enabling a more accurate reflection of the disease environment.
Professor Peter Lay, Director of the Vibrational Spectroscopy Core Facility at The University of Sydney says the new clarity around the mechanisms of deadly cerebral malaria – which claims the lives of 750,000 people globally each year – will inform new interventions for people at risk of the disease and opens up avenues of research into other brain diseases.
‘Previously we did not clearly understand processes involved in the disease, but our new evidence that the immune system is to blame for the initial damage, with subsequent oxidative stress inducing the death of brain tissues, means we can develop anti-inflammatory and anti-oxidant interventions that subdue the immune attack and reduce subsequent brain damage.
‘We believe our chemical-free multi-modal approach to imaging the brain can be applied to research across all chronic neurodegenerative disease and we plan to replicate this successful experimental approach to shed new light into the molecular processes that drive multiple sclerosis, motor neurone disease and Parkinson’s and Alzheimer’s diseases.’
Dr Tom Caradoc-Davies loads protein crystal samples into the path of the synchrotron beam on the Micro Crystallography (MX2) beamline, site of the new ACRF Detector.
Research across the country into how cancers begin and spread is set to be turbocharged, after the Australian Cancer Research Foundation (ACRF) last night awarded $2 million in funding for a new detector that will provide faster protein analysis at the Australian Synchrotron.
The ACRF Detector will enable the shape and function of proteins to be analysed on the Australian Synchrotron’s Micro Crystallography (MX2) beamline in a fraction of the time taken currently, providing a ten-fold increase in capacity crucial to accelerating cancer drug development.
Professor Michael Parker, Deputy Director of St Vincent’s Institute of Medical Research in Melbourne and co-Principal Investigator on the successful grant, says the ACRF investment in this key cancer research technology, available at only a handful of other synchrotron facilities around the world, will lead to better outcomes for people living with the disease.
‘Importantly, by increasing the capacity for drug development research in Australia, it is Australians with cancer who will be the first to benefit as novel treatments move from laboratories into clinical trials at our public hospitals.
Professor Parker says proteins, large molecules essential to all living organisms, are crucial to understanding disease and treatment targets.
‘With malfunctioning proteins causing many diseases, including cancer, arming researchers with clear representations of protein structures supports efforts to design drugs that target particular proteins, to boost their anti-cancer properties or suppress their cancer-enabling effects.’
Professor Andrew Peele, Director of the Australian Synchrotron, says the ACRF Detector will liberate researchers on the MX2 beamline, which is now at capacity.
‘The brilliant light of the MX2 beamline allows us to investigate the arrangement and activity of molecules involved in cancer and cancer treatments at a level of detail that is not possible at any other Australian research facility.
‘The increase in speed and quality of the data from the ACRF Detector is akin to shifting from dial-up to broadband, enabling more and better research outcomes that will improve our ability to combat disease.’
Professor Ian Brown, Chief Executive ACRF, says the new ACRF Detector will significantly increase protein analysis capability in Australia.
‘We hope research into even more protein structures and drug targets will enable the development of new treatments for cancer that could be produced in Australia and applied worldwide.
‘Most importantly, more researchers will gain answers much faster, shortening the time from laboratory research to the clinical testing of new cancer drugs.’
The ACRF Detector at the Australian Synchrotron will be operational in 2017; the investigative team leaders are Professor Andrew Peele from the Australian Synchrotron; Professor Michael Parker, St Vincent’s Institute for Medical Research; Professor Jamie Rossjohn and Professor James Whisstock, ARC Centre of Excellence in Advanced Molecular Imaging and Monash University; Dr Peter Czabotar, Walter and Eliza Hall Institute for Medical Research and Professor Charles Bond, The University of Western Australia.
· 'Science beams', Herald Sun, Thursday 10 December 2015
· ‘Cancer drug development gets boost with $2m grant to Australian Synchrotron’, ABC News online, Thursday 10 December 2015
· ‘Professor Andrew Peele discusses the ACRF Detector at the Australian Synchrotron’ on Triple R 102.7 FM, Wednesday 23 December 2015
Find out more:
· Visit Australian Cancer Research Foundation for the latest on their work enabling and equipping cancer research scientists to achieve things tomorrow that they could only dream of today
· For news, information and leading opinion on cancer treatment, prevention, diagnosis and cure, visit home.cancerresearch
Prime Minister Malcolm Turnbull announces details of the National Innovation and Science Agenda, with Industry, Innovation and Science Minister Christopher Pyne at CSIRO in Canberra today.
A $520 million, ten-year investment in operations will allow the Australian Synchrotron to further empower Australian researchers and industry to problem solve and innovate, with the Federal Government today announcing new funding for the landmark facility through the Australian Nuclear Science and Technology Organisation (ANSTO).
Speaking from Canberra at the release of the National Innovation and Science Agenda, Professor Andrew Peele, Director of the Synchrotron, said the long-term security will have dual benefits for the facility, the only one of its kind in Australia.
‘For many years now, securing ongoing funding has been a priority focus and has held us back from being able to put long-term plans in place.
‘Operational funding on this scale gives us the room we need to grow, to seek new partnerships, and to expand our beamline infrastructure to increase both the capacity and capability of the synchrotron.
‘This will make the Australian Synchrotron not only a formidable science facility, but a true research hub,’ he said.
Professor Peele said the announcement speaks volumes of ANSTO’s experience and expertise in operating landmark research infrastructure.
‘In adding this cutting-edge facility to ANSTO’s world-class line up of research platforms, the Federal Government recognises the importance of the Synchrotron to Australian research.’
Professor Peele acknowledged the ongoing support the facility has received from the research community and governments, including the Victorian Government, which was the driving force behind the synchrotron’s construction.
‘We will, of course, remain based within Victoria and I thank the Victorian Government for its incredible support – taking this from a concept to one of the most productive and effective synchrotron facilities in the world; with this announcement we can now repay that support by cementing the place of the Australian Synchrotron as one of the truly great national research facilities.’