First users on VMXm

First users from the University of Southampton investigated proteins involved in nutrient uptake of photosynthetic or cyanobacteria to understand how these phytoplankton thrive under scarce nutrient conditions.

The work has immense global significance for biofuels production and biotechnology. This beamline marks the completion of Diamond’s original Phase III funding on time and within budget.

First users have now been welcomed by Diamond Light Source, the UK’s national synchrotron light source on its new VMXm beamline. The Versatile Macromolecular Crystallography micro/nanofocus (VMXm) beamline becomes the 32nd operational beamline to open its doors to users, completing the portfolio of seven beamlines dedicated to macromolecular crystallography.
The unique VMXm beamline represents a significant landmark for Diamond. It is a specialist tuneable micro/nanofocus macromolecular crystallography (MX) beamline, with an X-ray beam size of less than 0.5 microns, allowing even the tiniest of samples to be analysed. Integrated into the ‘in vacuum’ sample environment is a scanning electron microscope, making VMXm a hybrid X-ray/cryoEM instrument for detecting and measuring data from nanocrystals. VMXm is aimed at research applications where the production of significant quantities of protein and crystals is difficult.

>Read more on the Diamond Light Source website

Image: Principal Beamline Scientist Dr Gwyndaf Evans with his team Dr Jose Trincao, Dr Anna Warren, Dr Emma Beale and Dr Adam Crawshaw. First users – Dr Ivo Tews from Biological Sciences at the University of Southampton and joint Diamond-Southampton PhD student Rachel Bolton investigating proteins involved in nutrient uptake of photosynthetic or cyanobacteria.

Funds for the latest generation of electron cryomicroscopy

The Polish Ministry of Science and Higher Education handed over to SOLARIS the official decision to establish the National Cryo-EM Centre at the Polish partner facility, granting the requested financial support.

The successful application is the result of an agreement and cooperation of 17 leading scientific institutions in Poland in the area of structural biology. This very unique nation-wide consortium, led by Dr. Sebastian Glatt (the Malopolska Centre of Biotechnology, Jagiellonian University, Kraków) and Dr. hab. Marcin Nowotny (the International Institute of Molecular and Cell Biology, Warsaw), was not only key to bring this breakthrough research technique to Poland, but also exemplifies how scientists from around the country are able to work efficiently together for a greater common goal. This state-of-the-art microscope will allow its users to follow the progress of other international research centres and will transfer Polish and international scientists into the first class of structural biology.

The advances made in cryo-EM have revolutionized the field of structural biology over the last decade. The increased recognition of this technology has also culminated in the Chemistry Nobel Prize being awarded to its creators in 2017. The development of this technique has opened up new research horizons, which resulted in a long list of groundbreaking studies published in the most prestigious scientific journals. Foremost, the anticipated results are extremely relevant for a better understanding of the function of the human body, of the formation of human diseases and of processes like aging, and can lead to the development of new effective therapies. Structural biology has already contributed to a huge progress in the treatment of various human diseases, including cancer, Alzheimer’s disease and obesity. Last but not least, the presence of a high-end cryo-electron microscope at SOLARIS means that Krakow will attract national and international structural biologists.

>Read more on the SOLARIS website

Image: The image of mimivirus made with the use of a cryo-electron microscope.
Credit: Xiao C, Kuznetsov YG, Sun S, Hafenstein SL, Kostyuchenko VA, et al. (2009) [CC BY 2.5]

The ESRF CryoEM excels in its first year

In November 2017, a Titan Krios cryo-electron microscope (cryo-EM) was inaugurated at the ESRF, the European Synchrotron, France. Data collected on this cryo-EM features in a Nature publication describing the activation cycle of a serotonin receptor, which is targeted by medication against chemotherapy- and radiotherapy-induced nausea.

“This publication is a true reward for us: the first one in less than a year from inauguration and we hope this kind of rewards will grow in number”, explains Isai Kandiah, ESRF scientist who runs the facility. “It shows the revolution that cryo-EM is leading in structural biology”, she adds. Thanks to cryo-EM, researchers can now freeze biomolecules, including membrane proteins of high medical importance, in several different conformations in action and visualise each of these to atomic resolution. Cryo-EM thus allows researchers to produce snapshots revealing the dynamics of proteins when they interact with other molecules, information that is crucial both for a basic understanding of life’s chemistry and for the development of pharmaceuticals. The user programme of the cryo-electron microscope at the ESRF is run jointly with the European Molecular Biology Laboratory (EMBL), the Institut de Biologie Structurale (IBS) and the Institut Laue-Langevin (ILL).

The research in Nature is a result of an international collaboration of scientists from the Institute of Structural biology (IBS-mixed research unit CEA-CNRS-University Grenoble Alps), CEA, CNRS, the Institut Pasteur, the University of Lorraine (France), the University of Copenhagen (Denmark), the University of Illinois (US) and the biotech company Theranyx. The focus of the paper, featuring data from the ESRF cryo-EM, is the activation cycle of the 5-HT3 receptor, belonging to the family of serotonin receptors. These receptors are well-known because they influence various biological and neurological processes such as anxiety, appetite, mood, nausea, sleep and thermoregulation, among others. Unlike the other serotonin receptors, which are G protein-coupled receptors, 5-HT3 is a neurotransmitter-gated ion channel and changes its conformation during activation. It is present in the brain, as well as in the enteric nervous system, the peripheral nervous system that drives the digestive tract.

>Read more on the European Synchrotron website

Image: A close-up view of the Cryo-EM at the ESRF.
Credit: S. Candé.

New cryo-EM Collaboration

UK set to be global leader in providing large-scale industrial access to Cryo-EM for drug discovery thanks to new collaboration.

Thermo Fisher Scientific and Diamond Light Source are creating a step change for life sciences sector, a one-stop shop for structural biology and one of largest cryo-EM sites in the world.
An agreement to launch a new cryo-EM capability for use in the life sciences industry sector by Thermo Fisher Scientific, one of the world leaders in high-end scientific instrumentation, and Diamond Light Source, the UK’s national synchrotron and one of the most advanced scientific facilities in the world, was announced today ahead of the official opening of the new national electron bio-imaging centre (eBIC) which will be held at Diamond on September 12th 2018.

This announcement confirms Diamond as one of the major global cryo-EM sites embedded with an abundance of complementary synchrotron-based techniques, and thereby, provides the life sciences sector with an offer not available anywhere else in the world.

Professor Dave Stuart, Life Sciences Director at Diamond and MRC Professor of Structural Biology at the University of Oxford, Department of Clinical Medicine, says, “Access to 21st century scientific tools to push the boundaries of scientific research is essential for both academia and industry, and what we have created here at Diamond is truly unique in the world in terms of size and scale. The new centre offers the opportunity for almost real-time physiology, capturing proteins in action at cryo-temperatures by flash-freezing them at various stages. What Diamond has created with eBIC is an integrated facility for structural biology, which will accelerate R&D for both industry and academic users. The additional advanced instruments made available by Thermo Fisher will position the UK as a global leader in providing large-scale industrial access to cryo-EM for drug discovery research. Our new collaboration provides a step change in our offer for industry users and helps ensure that R&D remains in the UK.”

>Read more on the Diamond Light Source website

Image: Close up sample loading Krios I.

Inauguration of a Cryo-electron microscope platform at the ESRF

A TITAN KRIOS cryo-electron microscope has been inaugurated at the ESRF, the European Synchrotron, in Grenoble, France. The inauguration took place in the presence of Ada Yonath, chemistry Nobel Prize laureate in 2009, Francesco Sette, Director General of the ESRF and all the partners that jointly run the facility with the ESRF: the European Molecular Biology Laboratory (EMBL), the Institut de Biologie Structurale (IBS) and the Institut Laue-Langevin (ILL). This cryo-electron microscope will provide Europe with a new, innovative and complementary facility for structural biology, serving a vibrant scientific community and addressing new biology and health challenges.

Read more on the ESRF website

Image: The team of the CRYO-EM. Credits: Stef Candé.

Growing a better polio vaccine

Researchers use plants as factories to produce a safer polio vaccine

Successful vaccination campaigns have reduced the number of polio cases by over 99% in the last several decades. However, producing the vaccines entails maintaining a large stock of poliovirus, raising the risk that the disease may accidentally be reintroduced.
Outbreaks can also occur due to mutation of the weakened poliovirus used in the oral vaccine. In addition, the oral vaccine has to be stored at cold temperatures. To address these shortcomings, an international team of researchers across the UK has engineered plants that produce virus-like particles derived from poliovirus, which can serve as a vaccine.
They report the success of this approach in a paper appearing in Nature Communications. The team confirmed the structure of the virus-like particles by cryo-electron microscopy at Diamond Light Source’s Electron Bio-Imaging Centre (eBIC) and showed that the particles effectively protected mice from infection with poliovirus. This proof-of-principle study demonstrates that a safe, effective polio vaccine can be produced in plants and raises the possibility of using the same approach to tackle other viruses.