Supporting World Cancer Day 2018

Diamond is proud to be supporting World Cancer Day and highlighting our role, working with our user community, in pioneering synchrotron research in every area of cancer – from developing a better understanding of how cancer cells work to delivering new cancer therapies.
Despite major advances in diagnosis and treatment, cancer still claims the lives of 8.8 million people every year around the world. About 4 million of these die prematurely (under the age of 70). World Cancer Day aims to raise the awareness of cancer and its treatment around the world. With the tagline ‘We can. I can.’, World Cancer Day is exploring how everyone can play their part in reducing the global burden of cancer.

Diamond has published over 900 publications in the last 12 months, with around 10% of these focusing on cancer. The wide-ranging research currently covers at least 12 cancer types, with many more general studies on the structure of cancer cells and pathways, potential drug targets and possible drug candidates. Building on last year’s review of some of the key studies in cancer that have taken place at Diamond, here is an update on studies that have been published in the last 12 months.

>Read more on the Diamond Light Source website

 

Modified antibody clarifies tumor-killing mechanisms

The structure of an antibody was modified to selectively activate a specific pathway of the immune system, demonstrating its value in killing tumor cells.

Immunotherapy—the use of the immune system to fight disease—has made tremendous progress in the fight against cancer. Antibodies such as immunoglobulin G (IgG) can identify and attack foreign or abnormal substances, including tumor cells. But to control and amplify this response, scientists need to know more about how elements of the immune system recognize tumor cells and trigger their destruction. There are two main pathways for this: antibody-dependent mechanisms and complement-dependent mechanisms.

The antibody pathway involves coating the surfaces of tumor cells with antibodies that recruit “natural killer” (NK) cells and macrophages (a type of white blood cell) to destroy the tumor cells. The complement pathway (so named because it complements the antibody pathway) also engages NK cells and macrophages and includes a third mechanism—a cascade of events culminating in tumor-cell destruction via a membrane attack complex (MAC).

>Read more on the ALS webpage

Image: extract of a schematic illustration (see on the ALS webpage)

Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how important bioinorganic electron transfer systems operate. Using a combination of very different, time-resolved measurement methods at DESY’s X-ray source PETRA III and other facilities, the scientists were able to show that so-called pre-distorted states can speed up photochemical reactions or make them possible in the first place. The group headed by Sonja Herres-Pawlis from the RWTH Aachen University  Michael Rübhausen from the University of Hamburg and Wolfgang Zinth from Munich’s Ludwig Maximilian University, is presenting its findings in the journal Nature Chemistry.

The scientists had studied the pre-distorted, “entatic” state using a model system. An entatic state is the term used by chemists to refer to the configuration of a molecule in which the normal arrangement of the atoms is modified by external binding partners such that the energy threshold for the desired reaction is lowered, resulting in a higher speed of reaction. One example of this is the metalloprotein plastocyanin, which has a copper atom at its centre and is responsible for important steps in the transfer of electrons during photosynthesis. Depending on its oxidation state, the copper atom either prefers a planar configuration, in which all the surrounding atoms are arranged in the same plane (planar geometry), or a tetrahedral arrangement of the neighbouring ligands. However the binding partner in the protein forces the copper atom to adopt a sort of intermediate arrangement. This highly distorted tetrahedron allows a very rapid shift between the two oxidation states of the copper atom.

>Read more on the PETRA III website

Image Caption: Entatic state model complexes optimize the energies of starting and final configuration to enable fast reaction rates (illustrated by the hilly ground). The work demonstrates that the entatic state principle can be used to tune the photochemistry of copper complexes.
Credit: RWTH Aachen, Sonja Herres-Pawlis

SXRF shows anthers have a craving for copper

Research links micronutrient copper with pollen fertility and seed/grain yield

The global demand for high-yield crops is increasing with growing population and decreasing farmland resources. These trends force the utilization of marginal lands for agricultural purposes. The bioavailability of essential mineral nutrients such as copper in these soils is often low, causing the reduced crop growth and fertility, and consequently low grain yield or even total crop failure. Although copper is recognized as an essential micronutrient for plant fertility, scientists still do not completely know which reproductive structures of plants require copper, how copper is delivered there and how copper transport processes are regulated. These questions are currently being addressed in the Vatamaniuk lab using model plants Arabidopsis thaliana and Brachypodium distachyon as well as a crop species, wheat, Triticum aestivum.

In studies using A. thaliana, the Vatamaniuk research group identified a new protein, CITF1, whose transcript accumulates in A. thaliana flowers during periods of copper deficiency. CITF1 acts as a transcription regulator: it regulates copper uptake into the roots and its delivery to flowers, working in tandem with SPL7 that is the central regulator of copper homeostasis in this plant species. When SPL7 and CITF1 do not function, as in the citf1 spl7 double mutant, its seedlings die and its pollen becomes infertile. Working with CHESS scientist, Rong Huang, at F3 beamline, a member of the Vatamaniuk research group, Ju-Chen Chia has shown that the sites of pollen production, anthers of flowers, accumulate the majority of the absorbed copper in A. thaliana. Huang and Chia also showed that copper accumulation was somewhat lower in anthers and carpels of the citf1 mutant and was further reduced in anthers and carpels of the spl7 mutant compared to wild-type plants (Fig. 1). They also showed that the majority of anthers of the citf1 spl7 double mutant lacked copper and that this deficiency resulted in pollen infertility.

>Read more on the CHESS website

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