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

 

Malaria in Action

Seeing the invisible

In 2007 Helen Saibil was at a conference in Australia. Amongst the presentations there happened to be talks on the parasites malaria and toxoplasma and how they infect mammalian cells, causing disease. Helen is a structural biologist and whilst listening she began to realise that her newly acquired skills -she was doing electron tomography of cells- might allow the researchers to see things they had never seen before.

Electron tomography reveals structures in the interiors of cells in great detail. What she hoped was that it could be used to look at the malaria parasites inside red blood cells [See images below] to get a better understanding of what they do there. Helen approached one of the speakers, Mike Blackman, then at the National Institute for Medical Research at Mill Hill in London, and so began a thriving collaboration. One that has produced the remarkable pictures of malaria parasites breaking out of infected human red blood cells on this page.

Helen Saibil and her colleagues used electron tomography to peer into malaria infected cells, looking at the parasites hiding and multiplying inside. The technique produces exquisitely detailed pictures able to reveal very tiny features, but it has one big drawback. Electrons cannot penetrate deep into the sample so it only works on very thinly sliced samples, much thinner than an individual cell. As a result it cannot be used to look at entire cells, or in this case red blood cells containing malaria parasites.

>Read more on the Diamond Light Source website

 

Synchrotron sheds light on the amphibious lifestyle of a new raptorial dinosaur

An exceptionally well-preserved dinosaur skeleton from Mongolia at ESRF.

The skeleton unites an unexpected combination of features that defines a new group of semi-aquatic predators related to Velociraptor. Detailed 3D synchrotron analysis allowed an international team of researchers to present the bizarre 75 million-year-old predator, named Halszkaraptor escuilliei, in Nature.

The study not only describes a new genus and species of bird-like dinosaur that lived during the Campanian stage of the Cretaceous in Mongolia but also sheds light on an unexpected amphibious lifestyle for raptorial dinosaurs.

>Read more on the ESRF website

Image: The team of scientists at ESRF’s BM05 beamline during the set up of Halszkaraptor escuilliei fossil. From left to right: Pascal Godefroit, Vincent Beyrand, Dennis Voeten, Paul Tafforeau, Vincent Fernandez, Andrea Cau.
Credit: ESRF/P.Jayet

 

 

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

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.

A mixtape for drug discovery

New method enables automated fast investigation of enzymatic processes

Scientists at DESY have developed a new method that enables automated and fast screening of promising drug candidates. This novel technique, called mix-and-diffuse serial synchrotron crystallography, can image the interaction of potential drug targets with drug candidates or other molecules. The concept has the potential to take structure and fragment based drug design to a new level, as the researchers write in the Journal of the International Union of Crystallography (IUCrJ).

>Read More on the PETRA III website

Image: Principle of the mix-and-diffuse serial synchrotron crystallography: protein crystals are mixed with a solution of a drug candidate and X-rayed on a tape running through the X-ray beam.
Credit: Beyerlein et al., IUCrJ 

Biochemistry and adaptive colouration of an exceptionally preserved juvenile fossil sea turtle

Johan Lindgren – together with colleagues abroad as well as at his own department and at the infrared microspectroscopy beamline D7 at the old MAX IV Laboratory in Lund – studied the biomolecular inventory of the fossil turtle. The researchers identified residues of several different molecules, including beta-keratin, eumelanin, haemoglobin, and tropomyosin. Eumelanin is a pigment that provides dark skin colour also in humans. Researchers at Lund University in Sweden have discovered well-preserved pigments and other biomolecules in a 54 million-year-old baby sea turtle. The molecular analyses show that the turtle’s shell contained pigments to protect it from harmful UV rays of the sun.

Read more on the MAX-IV website

Image: Holotype of Tasbacka danica. (a) Photograph of the fossil. Fo, fontanelle (the light colour is a result of sediment infill); Hyo, hyoplastron; Hyp, hypoplastron; Ne, neural; Nu, nuchal; Pe, peripheral; Py, pygal. Arrowheads indicate neural nodes. (b) Detail of the carapace with the sampled area demarcated by a circle. Co, costal; Hu, humerus; Sc, scapula. (c) Higher magnification image showing marginal scutes (arrowheads), pigmentations on bones (arrows), and a brown-black film covering the fontanelles (stars).

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.

World Polio Day

Are we nearing the end of the war on polio?

There was a time when the word itself was enough to strike fear into the hearts of people around the world. Polio: a highly infectious virus that could shatter young lives in the blink of an eye. On the 24th of October, we mark World Polio Day, and this is something worth celebrating. Because whilst the story isn’t over yet, it may well be nearing its end.

Polio has been around since before records began, but it wasn’t until the early-twentieth century that epidemics began to sweep through communities in Europe and America, affecting many thousands of children and families.

It’s hard to underestimate the terror once caused by polio. At its height in the 1950s, parents routinely lived in fear of their children becoming quarantined, paralysed or even worse. It was a dark time in medical history but, despite this, polio really is a success story for modern science.

#weekendusers Searching for the secrets of butterfly colours

Butterfly colour has always amazed scientists, who are trying to find the origins of these vivid tones in order to maybe one day be able to reproduce them. Researchers from the University of Sheffield (UK) have come to the ESRF to study the subtle differences in the structural colour elements of Heliconius butterflies, and link them to the genetics that controls these structures.

Read more on the ESRF website

Image credit: A Heliconius butterfly. Credit: Dany 13. https://www.flickr.com/photos/dany13/11465883596

A study reveals half billion year old fabrication mystery of nature

A study published in Science Advances reveals a half billion year old fabrication concept, employed by nature, which only recently has been used by mankind to produce novel technologically relevant nanomaterials. Using data from three different X-ray imaging and analysis instruments at the ESRF, the European Synchrotron, Grenoble, France, the international team of scientists unravels how living organisms create very complex highly regular glass structures.

Read more on the ESRF website

Image credit: Electron microscopy image of glass spicules form the sponge Geodia cydonium. Credits : Igor Zlotnikov, B CUBE–Center for Molecular Bioengineering, Technische Universität Dresden

The Brain Revisited

How does it work? Mazes of neurons all joined together by trillions of synaptic connections…

Everything we do – from writing our name to remembering it – is the result of billions of nerve cells, also known as neurons, firing electro-chemical signals through our brains. The way we experience the world around us is tied up in these mazes of neurons, all joined together by trillions of synaptic connections. Thanks to all this processing power, our brains are more complex than any computer system on earth.

The astonishing intricacy of our brains allows us to perform incredible feats of thought. But there’s also a downside to possessing all this brain power. With all that complex machinery at play, errors in the system can spell big trouble for our health. Neurodegenerative conditions like Parkinson’s and Alzheimer’s are linked to problems with the brain’s neural network. Because these networks are so labyrinthine, we don’t yet understand the brain and, in turn, how to combat neurological conditions, as well as we’d like.

New approach to imaging single biological particles

As part of an international collaboration, scientists at European XFEL have developed and tested a novel approach for processing data from single biological particles such as proteins and viruses. Based on an idea first proposed over 40 years ago, the new method overcomes several problems of traditional approaches and could also have applications for other structural biology methods. The method is published today in the journal Physical Review Letters.

Read more on the European XFEL website

Image: Schematic illustration of the new approach. Many X-ray diffraction snapshots recorded in the XFEL experiment (left) […]. Source: European XFEL website

Researchers explore ways to remove antibiotics polluting lakes and rivers

Pre-treated barley straw is showing promise as an environmentally-friendly material.

Pre-treated barley straw could be used to help soak up certain types of antibiotics polluting waterways. Pharmaceuticals, including antibiotics, are an increasingly common pollutant in water systems, says Catherine Hui Niu, associate professor in the Department of Chemical and Biological Engineering at the University of Saskatchewan.

After pharmaceuticals are used in humans and animals, traces are excreted and end up in sewage and, from there, into the environment. Their presence in waterways has raised concerns about potential risks to human health and ecosystems. To date there has been no effective way to remove them from water sources.

There are some materials that attract pharmaceutical pollutants to them in a process called adsorption, and could hypothetically be used to help remove them from water, says Niu. But their adsorption capacities need to be enhanced to make them useful for large scale clean-up efforts.

New insights about malaria parasites infection mechanisms

Unraveled details about how the malaria parasite acts after invading the red blood cells.

This highlight has been possible thanks to two advanced microscope techniques combination: X-ray fluorescence microscopy and soft X-rays tomography, this one conducted in ALBA Synchrotron. Infected red blood cells image analysis offer new information that could yield new drugs design against malaria, an illness that claims over 400.000 lives each year.
Plasmodium falciparum causes the malaria disease. This parasite, transmitted through mosquito sting, infects red blood cells of its victim. Once inside, it uses hemoglobin (the protein in charge of oxygen transport) as a nutrient. When it is digested, iron is released in a form of heme molecules. These heme molecules are toxic to the parasite, but it has a strategy to make them harmless: it packs heme in pairs and finally they are packed forming hemozoin crystals. In this way, poisonous iron is locked up and no longer will be a threat for the parasite.


>Read More on the ALBA website

Infographic: Model for biochemistry processes that occur inside the parasite. The parasite takes the hemoglobin from the red blood cell (RBC)
1 and digests it inside the digestive vacuole (DV)
2. as a consequence, heme groups are released
3. and HDP protein packages them in pairs (heme dimers)
4. finally, in the crystallization process these dimers are converted in hemozoin crystals
5. blue arrow points out the suggested feedback mechanism that regulates hemoglobin degradation.