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


Scientists use machine learning to speed discovery of metallic glass

In a new report, they combine artificial intelligence and accelerated experiments to discover potential alternatives to steel in a fraction of the time.

Blend two or three metals together and you get an alloy that usually looks and acts like a metal, with its atoms arranged in rigid geometric patterns.

But once in a while, under just the right conditions, you get something entirely new: a futuristic alloy called metallic glass that’s amorphous, with its atoms arranged every which way, much like the atoms of the glass in a window. Its glassy nature makes it stronger and lighter than today’s best steel, plus it stands up better to corrosion and wear.

Even though metallic glass shows a lot of promise as a protective coating and alternative to steel, only a few thousand of the millions of possible combinations of ingredients have been evaluated over the past 50 years, and only a handful developed to the point that they may become useful.

Now a group led by scientists at the Department of Energy’s SLAC National Accelerator Laboratory, the National Institute of Standards and Technology (NIST) and Northwestern University has reported a shortcut for discovering and improving metallic glass – and, by extension, other elusive materials – at a fraction of the time and cost.

>Read more on the SLAC website

Image: Fang Ren, who developed algorithms to analyze data on the fly while a postdoctoral scholar at SLAC, at a Stanford Synchrotron Radiation Lightsource beamline where the system has been put to use.
Credit: Dawn Harmer/SLAC National Accelerator Laboratory

Gold protein clusters could be used as environmental and health detectors

Peng Zhang and his collaborators study remarkable, tiny self-assembling clusters of gold and protein that glow a bold red. And they’re useful: protein-gold nanoclusters could be used to detect harmful metals in water or to identify cancer cells in the body.
“These structures are very exciting but are very, very hard to study. We tried many different tools, but none worked,” says Zhang, a Dalhousie University professor.

Peng Zhang and his collaborators study remarkable, tiny self-assembling clusters of gold and protein that glow a bold red. And they’re useful: protein-gold nanoclusters could be used to detect harmful metals in water or to identify cancer cells in the body.

“These structures are very exciting but are very, very hard to study. We tried many different tools, but none worked,” says Zhang, a Dalhousie University professor.

>Read more on the Canadian Light Source website

Image: The protein-gold structure. The protein, which both builds and holds in place the gold cluster, is shown in grey.

Shedding new light on laser additive manufacturing

Additive manufacturing (AM, also known as 3D printing) allows us to create incredibly complex shapes, which would not be possible using traditional manufacturing techniques. However, objects created using AM have different properties from traditional manufacturing routes, which is sometimes a disadvantage.

Laser additive manufacturing (LAM) uses a laser to fuse together metallic, ceramic or other powders into complex 3D shapes, layer by layer. The cooling rates are extremely rapid, and since they are unlike conventional processes we don’t know the optimal conditions to obtain the best properties, delaying the uptake of LAM in the production of safety-critical engineering structures, such as turbine blades, energy storage and biomedical devices. We need a method to see inside the process of LAM to better understand and optimise the laser-matter interaction and powder consolidation mechanisms.

Based in the Research Complex at Harwell, a team of researchers have worked with scientists at I12, the Joint Engineering Environment Processing (JEEP) beamline and the Central Laser Facility to build a laser additive manufacturing machine which operates on a beamline, allowing you to see into the heart of the process, revealing the underlying physical phenomena during LAM.

>Read more on the Diamond Light Source website

Picture: The Additive Manufacturing Team from the Research Complex at Harwell on the Joint Engineering Environment Processing (JEEP, I12) beamline. The Laser Additive Manufacturing Process Replicator (or LAMPR) on the right is used to reveal the underlying physical phenomena during LAM.

New Diamond SESAME Rutherford training programme underway

First four fellows welcomed to new training programme

Diamond has welcomed the first four fellows on the newly created Diamond SESAME Rutherford Fellowship Training Programme. The result of a £1.5 million grant from the Department for Business, Energy and Industrial Strategy (BEIS), Diamond will use the funding to expand its training and development support of SESAME, a unique Middle East project.

Up to 25 delegates will benefit from training in areas of science and engineering associated with the construction and operation of SESAME (Synchrotron light for Experimental Science and Applications in the Middle East) in Jordan. The Middle East’s first major international research centre, the SESAME light source involves members from Cyprus, Egypt, Iran (Islamic Republic of), Israel, Jordan, Pakistan, the Palestinian Authority and Turkey.

Andrew Harrison, CEO of Diamond, explains, “SESAME represents a unique project for the Middle East region because of the excellent opportunity to stimulate and support scientific and technical activity, training and engagement in the region.  Because SESAME focuses on areas of local importance – such as water supply, energy, health and the environment – we are keen to nurture new talent and share our skills. This significant grant will enable us to build stronger links.”

>Read more on the Diamond Light Source website

Image: Fellows, Mentors and Programme Support
Credit: Diamond Light Source

Unravelling the great vision of flies

Fruit flies have a much better vision than what was previously believed in the scientific community.

Researchers from the University of Sheffield (UK), the University of Oulu (Finland), Max IV (Sweden) and University of Szeged (Hungary) are on ID16B trying to find out what happens in the photoreceptors in these insects’ eyes.

“It had always been claimed that fly’s eyesight was very basic, but I couldn’t believe that after so many centuries of evolution this was still the case”, explains Mikko Juusola, head of the Centre for Cognition in Small Brains at Sheffield University. So he started studying vision in fruit flies a decade ago and last year himself and his team debunked previous hypothesis: they proved that insects have a much better vision and can see in far greater detail than previously thought.

Insects’ compound eyes typically consist of thousands of tiny lens-capped ‘eye-units’, which together should capture a low-resolution pixelated image of the surrounding world. In contrast, the human eye has a single large lens, and the retinal photoreceptor array underneath it is densely-packed, which allows the eye to capture high-resolution images. This is why it was believed that insects did not have a good eyesight. Until Juusola came in the picture.

>Read more on the European Synchrotron website

Image: Marko Huttula (University of Oulu, Finland), Jussi-Petteri Suuronen (ESRF) and Mikko Juusola (University of Sheffield, UK) on ESRF’s ID16B beamline. Credit: ©ESRF/C.Argoud

Inscuteable: No longer inscrutable

The structure and function of a controller of stem cell division

An important complex forming the core of the cell division apparatus in stem cells has been imaged using the Macromolecular Crystallography beamlines, I04 and I04-1 at Diamond Light Source. As recently reported in Nature Communications, the spindle orientation protein known as LGN bound to an adapter protein known as Inscuteable in a tetrameric arrangement, which drove asymmetric stem cell division.

Stem cells are undifferentiated cells that have the capacity to differentiate into specialised cells. In a developing embryo, stem cells are the foundation of all other cells, whereas in adults, they can aid repair by replenishing lost tissue. To ensure a physiological balance between differentiated and undifferentiated cells, stem cells undergo asymmetric division to give rise to an identical daughter stem cell and a differentiated cell.

Asymmetric division occurs when there is an unequal segregation of cellular contents. For this to occur, the line of division of the cell (known as the axis) must be carefully positioned. The stem cells use polarity proteins, such as Par3, to determine the location of this axis, and then proteins such as LGN and Inscuteable (Insc) help to align the mitotic spindle to the axis of polarity.

Despite the importance of such a process, little is known about the interactions between the proteins. Dr Marina Mapelli, Group Leader at the European Institute of Oncology in Milan and Dr Simone Culurgioni, Post-Doctoral Research Associate here at Diamond, along with scientists from the Italian Institute of Technology, plus the European Molecular Biology Laboratory in Grenoble set out to solve the crystal structure of LGN bound to Insc. They saw that the proteins were intertwined in a fascinating tetrameric arrangement and found that Insc alone had impressive anti-proliferative properties.

>Read more on the Diamond Light Source website

Figure : On the left, a stem cell orienting (movement highlighted by the red arrow) its mitotic spindle (in green) in order to partition its cellular components (in pink and yellow) unequally in the two daughter cells; one is retaining the stem state (in pink) and the other one is committed to differentiate (in yellow). On the right, the structure of Insc:LGN complex governing this asymmetric cell division process. Insc:LGN complex assembles in highly stable intertwinned tetrameric structure (Insc in blue and purple, LGN in yellow and orange respectively
Entire image here.

Serial crystallography develops by leaps and bounds at the ESRF

Serial crystallography is a new way of studying macromolecular structures using synchrotron and X-FEL sources around the world.

The Structural Biology group at the ESRF is continuously developing new methods to advance the field. Two articles describing advances made are published today in Acta Crystallographica Section D.

“On the Structural Biology Group beamlines one of the ultimate aims is that users can define protocols for experiments, click ‘go’ and let the experiments run by themselves”, explains Gordon Leonard, head of the Structural Biology group at the ESRF. With this idea in mind and to get as much information as possible from the samples available, the team has already adopted serial crystallography, a technique which involves taking diffraction data from many, sometimes hundreds or thousands, of crystals in order to assemble a complete dataset, piece by piece. Indeed, the members of the group are constantly developing new ways to improve the method through collaboration involving scientists from the ESRF, DESY, the Hamburg Centre for Ultrafast Imaging, the European X-FEL and the University of Hamburg.

>Read more on the European Synchrotron website

Image: Daniele de Sanctis on the ID29 beamline.
Credit: S. Candé.

Climate change and its effects on Rocky Mountain alpine lakes

Alpine lakes in the Rocky Mountains are important biological hot spots of that ecosystem. These lakes do not have enough nutrients to support large amounts of aquatic life because of the cold climate in the surrounding watershed. Rather, the lakes are home to oligotrophs, organisms that grow slowly and can survive in harsh aquatic environments. The lakes also host a variety of cold-water fish, such as trout, that are preyed upon by birds, including osprey and bald eagles.

Researchers from University of Wyoming, U.S. Geological Survey, and the Canadian Light Source conducted experiments at the CLS on the fine dust that is deposited to the Rocky Mountains to learn more about how the alpine lakes could be affected by climate change. They looked specifically at phosphorus in dust and how it is made available to the organisms in the cold lakes and streams, because phosphorus is one of the major limiting nutrients, and its availability could affect the functions and properties of alpine lake ecosystems.

>Read more on the Canadian Light Source website