Tagged: CryoEM-cryo electron microscopy Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 8:43 pm on July 22, 2021 Permalink | Reply
    Tags: "Laser improves the time resolution of CryoEM", , , , CryoEM-cryo electron microscopy, In cryoEM samples are embedded in vitreous ice-a glass-like form of ice that is obtained when water is frozen so rapidly that crystallization cannot occur., , , Scientists at EPFL’s School of Basic Sciences has developed a cryoEM method that can capture images of protein movements at the microsecond (a millionth of a second) timescale., , The instrument forms images using a beam of electrons instead of light.   

    From Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH): “Laser improves the time resolution of CryoEM” 

    From Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH)

    Nik Papageorgiou

    EPFL scientists have devised a new method that can speed up the real-time observation capabilities of cryo-electron microscopy.

    Cryo-Electron Microscope


    In 2017, Jacques Dubochet, Joachim Frank, and Richard Henderson won the Nobel Prize in Chemistry for their contributions to cryo-electron microscopy (cryoEM), an imaging technique that can capture pictures of biomolecules such as proteins with atomic precision.

    In cryoEM samples are embedded in vitreous ice-a glass-like form of ice that is obtained when water is frozen so rapidly that crystallization cannot occur. With the sample vitrified, high-resolution pictures of their molecular structure can be taken with an electron microscope, an instrument that forms images using a beam of electrons instead of light.

    CryoEM has opened up new dimensions in life sciences, chemistry, and medicine. For example, it was recently used to map the structure of the SARS-CoV-2 spike protein, which is the target of many of the COVID-19 vaccines.

    Proteins constantly change their 3D structure in the cell. These conformational rearrangements are integral for proteins to perform their specialized functions, and take place within millionths to thousandths of a second. Such fast movements are too fast to be observed in real time by current cryoEM protocols, rendering our understanding of proteins incomplete.

    But a team of scientists led by Ulrich Lorenz at EPFL’s School of Basic Sciences has developed a cryoEM method that can capture images of protein movements at the microsecond (a millionth of a second) timescale. The work is published in Chemical Physics Letters.

    The method involves rapidly melting the vitrified sample with a laser pulse. When the ice melts into a liquid, there is a tunable time window in which the protein can be induced to move in the way they do in their natural liquid state in the cell.


    “Generally speaking, warming up a cryo sample causes it to de-vitrify,” says Ulrich Lorenz. “But we can overcome this obstacle by how quickly we melt the sample.”

    After the laser pulse, the sample is re-vitrified in just a few microseconds, trapping the particles in their transient configurations. In this “paused” state, they can now be observed with conventional cryoEM methods.

    “Matching the time resolution of cryoEM to the natural timescale of proteins will allow us to directly study processes that were previously inaccessible,” says Lorenz.

    The team of scientists tested their new method by disassembling proteins after structurally damaging them, and trapping them in partially unraveled configurations.

    See the full article here .


    Please help promote STEM in your local schools.

    Stem Education Coalition

    EPFL bloc

    EPFL campus

    The Swiss Federal Institute of Technology in Lausanne [EPFL-École polytechnique fédérale de Lausanne] (CH) is a research institute and university in Lausanne, Switzerland, that specializes in natural sciences and engineering. It is one of the two Swiss Federal Institutes of Technology, and it has three main missions: education, research and technology transfer.

    The QS World University Rankings ranks EPFL(CH) 14th in the world across all fields in their 2020/2021 ranking, whereas Times Higher Education World University Rankings ranks EPFL(CH) as the world’s 19th best school for Engineering and Technology in 2020.

    EPFL(CH) is located in the French-speaking part of Switzerland; the sister institution in the German-speaking part of Switzerland is the Swiss Federal Institute of Technology ETH Zürich [Eidgenössische Technische Hochschule Zürich)](CH) . Associated with several specialized research institutes, the two universities form the Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles polytechniques fédérales] (CH) which is directly dependent on the Federal Department of Economic Affairs, Education and Research. In connection with research and teaching activities, EPFL(CH) operates a nuclear reactor CROCUS; a Tokamak Fusion reactor; a Blue Gene/Q Supercomputer; and P3 bio-hazard facilities.

    The roots of modern-day EPFL(CH) can be traced back to the foundation of a private school under the name École spéciale de Lausanne in 1853 at the initiative of Lois Rivier, a graduate of the École Centrale Paris (FR) and John Gay the then professor and rector of the Académie de Lausanne. At its inception it had only 11 students and the offices was located at Rue du Valentin in Lausanne. In 1869, it became the technical department of the public Académie de Lausanne. When the Académie was reorganised and acquired the status of a university in 1890, the technical faculty changed its name to École d’ingénieurs de l’Université de Lausanne. In 1946, it was renamed the École polytechnique de l’Université de Lausanne (EPUL). In 1969, the EPUL was separated from the rest of the University of Lausanne and became a federal institute under its current name. EPFL(CH), like ETH Zürich(CH), is thus directly controlled by the Swiss federal government. In contrast, all other universities in Switzerland are controlled by their respective cantonal governments. Following the nomination of Patrick Aebischer as president in 2000, EPFL(CH) has started to develop into the field of life sciences. It absorbed the Swiss Institute for Experimental Cancer Research (ISREC) in 2008.

    In 1946, there were 360 students. In 1969, EPFL(CH) had 1,400 students and 55 professors. In the past two decades the university has grown rapidly and as of 2012 roughly 14,000 people study or work on campus, about 9,300 of these being Bachelor, Master or PhD students. The environment at modern day EPFL(CH) is highly international with the school attracting students and researchers from all over the world. More than 125 countries are represented on the campus and the university has two official languages, French and English.


    EPFL is organised into eight schools, themselves formed of institutes that group research units (laboratories or chairs) around common themes:

    School of Basic Sciences (SB, Jan S. Hesthaven)

    Institute of Mathematics (MATH, Victor Panaretos)
    Institute of Chemical Sciences and Engineering (ISIC, Emsley Lyndon)
    Institute of Physics (IPHYS, Harald Brune)
    European Centre of Atomic and Molecular Computations (CECAM, Ignacio Pagonabarraga Mora)
    Bernoulli Center (CIB, Nicolas Monod)
    Biomedical Imaging Research Center (CIBM, Rolf Gruetter)
    Interdisciplinary Center for Electron Microscopy (CIME, Cécile Hébert)
    Max Planck-EPFL Centre for Molecular Nanosciences and Technology (CMNT, Thomas Rizzo)
    Swiss Plasma Center (SPC, Ambrogio Fasoli)
    Laboratory of Astrophysics (LASTRO, Jean-Paul Kneib)

    School of Engineering (STI, Ali Sayed)

    Institute of Electrical Engineering (IEL, Giovanni De Micheli)
    Institute of Mechanical Engineering (IGM, Thomas Gmür)
    Institute of Materials (IMX, Michaud Véronique)
    Institute of Microengineering (IMT, Olivier Martin)
    Institute of Bioengineering (IBI, Matthias Lütolf)

    School of Architecture, Civil and Environmental Engineering (ENAC, Claudia R. Binder)

    Institute of Architecture (IA, Luca Ortelli)
    Civil Engineering Institute (IIC, Eugen Brühwiler)
    Institute of Urban and Regional Sciences (INTER, Philippe Thalmann)
    Environmental Engineering Institute (IIE, David Andrew Barry)

    School of Computer and Communication Sciences (IC, James Larus)

    Algorithms & Theoretical Computer Science
    Artificial Intelligence & Machine Learning
    Computational Biology
    Computer Architecture & Integrated Systems
    Data Management & Information Retrieval
    Graphics & Vision
    Human-Computer Interaction
    Information & Communication Theory
    Programming Languages & Formal Methods
    Security & Cryptography
    Signal & Image Processing

    School of Life Sciences (SV, Gisou van der Goot)

    Bachelor-Master Teaching Section in Life Sciences and Technologies (SSV)
    Brain Mind Institute (BMI, Carmen Sandi)
    Institute of Bioengineering (IBI, Melody Swartz)
    Swiss Institute for Experimental Cancer Research (ISREC, Douglas Hanahan)
    Global Health Institute (GHI, Bruno Lemaitre)
    Ten Technology Platforms & Core Facilities (PTECH)
    Center for Phenogenomics (CPG)
    NCCR Synaptic Bases of Mental Diseases (NCCR-SYNAPSY)

    College of Management of Technology (CDM)

    Swiss Finance Institute at EPFL (CDM-SFI, Damir Filipovic)
    Section of Management of Technology and Entrepreneurship (CDM-PMTE, Daniel Kuhn)
    Institute of Technology and Public Policy (CDM-ITPP, Matthias Finger)
    Institute of Management of Technology and Entrepreneurship (CDM-MTEI, Ralf Seifert)
    Section of Financial Engineering (CDM-IF, Julien Hugonnier)

    College of Humanities (CDH, Thomas David)

    Human and social sciences teaching program (CDH-SHS, Thomas David)

    EPFL Middle East (EME, Dr. Franco Vigliotti)[62]

    Section of Energy Management and Sustainability (MES, Prof. Maher Kayal)

    In addition to the eight schools there are seven closely related institutions

    Swiss Cancer Centre
    Center for Biomedical Imaging (CIBM)
    Centre for Advanced Modelling Science (CADMOS)
    École cantonale d’art de Lausanne (ECAL)
    Campus Biotech
    Wyss Center for Bio- and Neuro-engineering
    Swiss National Supercomputing Centre

  • richardmitnick 2:15 pm on October 21, 2020 Permalink | Reply
    Tags: "World record resolution in cryo electron microscopy", CryoEM-cryo electron microscopy, Max Planck Institut für biophysikalische Chemie(DE), Since the outbreak of the Covid-19 pandemic scientists around the world have been solving 3D structures of important key proteins of the novel coronavirus.   

    From Max Planck Institut für biophysikalische Chemie(DE): “World record resolution in cryo electron microscopy” 

    From From Max Planck Institut für biophysikalische Chemie(DE)

    October 21, 2020
    Dr. Carmen Rotte
    Public relations office
    Max Planck Institut für biophysikalische Chemie(DE), Göttingen
    +49 551 201-1304

    Prof. Dr. Holger Stark
    Department of Structural Dynamics
    Max Planck Institut für biophysikalische Chemie(DE), Göttingen
    +49 551 201-1305

    Novel technique developed by Max Planck researchers in Göttingen visualizes individual atoms in a protein with cryo electron microscopy for the first time.

    Holger Stark from the Max Planck Institut für biophysikalische Chemie(DE), Göttingen and his team have broken a crucial resolution barrier in cryo electron microscopy. For the first time, his group succeeded in observing individual atoms in a protein structure and taking the sharpest images ever with this method. Such detailed insights make it easier to understand how proteins do their work or cause diseases in the living cell. The technique can also be used in the future to develop new drugs.

    A part of the apoferritin protein (yellow) with a tyrosine side chain highlighted in grey. The amino acid tyrosine consists of several atoms that are individually recognizable in the structure (red grid structures). © Max Planck Institut für biophysikalische Chemie(DE)/ Holger Stark.

    Since the outbreak of the Covid-19 pandemic, scientists around the world have been solving 3D structures of important key proteins of the novel coronavirus. Their common goal is to find docking sites for an active compound which can combat the pathogen effectively.

    One method applied for that is cryo electron microscopy (cryo-EM), which can be used to make three-dimensional structures of biomolecules visible. As these are structurally highly flexible this is no easy task. To capture the fuzzy molecules without damaging them, they are cooled down extremely quickly, or shock-frozen so to speak. The frozen samples are thereafter bombarded with electrons, and the resulting images are recorded. Using these, the three-dimensional structure of the molecules can then be calculated. Three pioneers of this technique, Jacques Dubochet, Joachim Frank, and Richard Henderson, received the Nobel Prize in Chemistry for the development of cryo-EM in 2017.

    World record for resolution allows to see individual atoms in proteins.

    Stark’s group has now broken the cryo-EM resolution barrier with a unique cryo electron microscope newly developed by this team. “We equipped our device with two additional electron-optical elements to further improve image quality and resolution. These ensure that imaging errors of optical lenses, so-called aberrations, no longer play a role,” explains the Max Planck director. His doctoral student Ka Man Yip adds: “Electron microscopes are optical instruments and physically resemble a camera. The aberrations of an electron microscope interfere in cryo-EM in much the same way as those of a camera in photography. For a much improved image quality it was therefore crucial to avoid these aberration errors.”

    Using the new microscope, the scientists have taken more than one million images of the protein apoferritin to map the molecular structure with a resolution of 1.25 angstroms. One angstrom is equivalent to a ten millionth of a millimeter. “We now visualize single atoms in the protein – a milestone in our field,” explains structural biologist Stark. “For us, it was like putting super glasses on the microscope. The new structure reveals details never seen before: We can even see the density for hydrogen atoms and single atom chemical modifications.”

    The great potential of cryo-EM for imaging of high-resolution 3D protein structures was also demonstrated by colleagues at the Medical Research Council Laboratory of Molecular Biology in Cambridge (UK). They achieved a similarly high resolution using a different approach. “It is now conceivable that cryo-EM will in future be able to achieve even subatomic resolutions,” says the researcher.

    Basis for structure-based drug design

    But what is the benefit of being able to study a protein structure with such unprecedented atomic resolution? To understand how a man-made machine works, one has to observe its components directly at work. This is also true for proteins – the nanomachines of living cells. To get an idea how they carry out their tasks, one has to know the exact position of all atoms of the protein.

    Such detailed insights are also relevant for structure-based drug design. Compounds for drugs are customized in a way that they bind to viral proteins, for example, and block their function. But what is the underlying mechanism of inhibition? Researchers can only elucidate and understand this if they can observe at atomic level how a compound and a viral protein interact. Such novel insights help to improve molecules for drugs and reduce side effects. “With breaking this cryo-EM resolution barrier, the technique has reached a level where the benefits for pharmaceutical developments are directly visible,” says Stark.

    Science paper:
    Atomic-resolution protein structure determination by cryo-EM

    See the full article here.


    Please help promote STEM in your local schools.

    Stem Education Coalition

    At Max Planck Institut für biophysikalische Chemie(DE) , we investigate how molecules interact to perform their various tasks – in a living cell but also in inanimate nature.

    We want to understand, for example, which mechanisms control and regulate life processes: How is the genetic information translated into proteins? How do nerve cells communicate with each other? How does the cell solve logistic tasks? On the level of organisms, we are interested in how a living being develops from a single egg cell and how the sleep-wake rhythm is controlled.

    Notwithstanding the above, we investigate how energy is converted between molecules at surfaces or how molecules may be used to improve light microscopy to molecular resolution.

    We are convinced that great scientific discoveries can be made when scientists of different fields and research cultures – such as physics, biology, and chemistry – are brought together and openly exchange ideas.

    Not least for this reason researchers at our institute achieved breakthroughs such as the relaxation methods, which allow the measurement of extremely fast reactions (Nobel Prize to physicochemist Manfred Eigen 1967), the patch clamp methods to measure ion fluxes across membranes (Nobel Prize to physicist Erwin Neher and physician Bert Sakmann 1991), the far-field microscopy on the nanometer scale, which reaches a resolution of up to a few nanometers (Nobel Prize to physicist Stefan W. Hell 2014), as well as magnetic resonance imaging, nuclear magnetic spin resonance spectroscopy, optical spectroscopy, or computer simulations.

    More about our research may be found here.

  • richardmitnick 10:19 am on February 19, 2018 Permalink | Reply
    Tags: , , C1 complex, CryoEM-cryo electron microscopy, CryoET-Cryo electron tomography, U Utrecht   

    From U Utrecht: “Unexpected immune activation illustrated in the cold” 

    Utrecht University

    15 February 2018

    Monica van der Garde
    Public Information Officer
    +31 (0)6 13 66 14 38

    Press Office Leiden University Medical Center
    +31 6 11 37 11 46
    +31 71 526 8005

    Combining CryoEM and CryoET lets researchers see the C1 complex in 3D (coloured model) bound to antibodies in a native state (background).

    Researchers at Utrecht University and Leiden University Medical Center, the Netherlands, have for the first time made a picture of an important on-switch of our immune system. Their novel technical approach already led to the discovery of not one, but two ways in which the immune system can be activated. This kind of new insights are important for designing better therapies against infections or cancer, according to team leaders Piet Gros and Thom Sharp. Their findings are published on February 16, 2018 in the journal Science.

    When invading microbes, viruses and tumours are detected in our bodies, our antibodies engage in an immediate defence strategy. They quickly raise warning signs on these aberrant surfaces that alert our body’s immune system of a security breach. This is the entry cue of several molecules, together called the C1 complex, that stick to the surface of the rogue cell and eliminate it from our body. Until recently, it was unknown how exactly invaders were recognized, and how this C1 complex was activated.


    Studying the C1 complex has been challenging since its components often clump together when taken out of their natural environment into a lab setting. Together with the international biotech company Genmab A/S, researchers from Utrecht University and Leiden University Medical Center have now developed a unique technical approach to studying it in a more natural environment – and discovered more than expected.

    Life-like detailed picture

    In order to capture the binding and interaction of the complex, Piet Gros, Utrecht University and Thom Sharp, Leiden University Medical Center, combined two imaging techniques, cryo electron microscopy (CryoEM) and cryo electron tomography (CryoET). “These technologies are exploding in the field,” describes Thom Sharp, “and each method gives us different but complementary information on the same complex.” When combined, these methods provide a more life-like detailed picture of the system.

    Reconstruction into a 3D representation

    For CryoEM, think of taking thousands of copies of the same convoluted complex and scattering them onto the sticky side of a piece of tape. The camera is in a fixed position and takes pictures of these particles, which may have landed right-side-up, on its side, on a point. CryoET, on the other hand, can image the complex in a more natural environment, as it is bound to the cell surface. It takes images from different angles of the complex, similar to a CT scan, where the particle rotates within the instrument. For both techniques, images are then reconstructed into a 3D representation of the complex.

    Very different mechanisms identified

    The researchers were surprised to find not one, but two ways in which the immune system can be activated: by physical distortion and by cross-activation. In some cases, the configuration of danger signals on a cell’s surface is sparse, and when antibodies bind, the entire complex must physically adjust or distort itself to properly fit. This adjustment of a single complex can set off an immune response. In other situations, where the danger signals are dense, multiple C1 complexes can help activate each other, like a neighbourhood watch system.

    First report

    This is the first report of two independent ways by which our immune system can be activated. In addition, the combination of CryoEM and CryoET enabled the visualization of details of these interactions that may enable researchers to create more specific therapeutics that can activate, slow down or stop the cascade of signals within our immune system.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Utrecht University (UU; Dutch: Universiteit Utrecht, formerly Rijksuniversiteit Utrecht) is a university in Utrecht, the Netherlands. It is one of the oldest universities in the Netherlands. Established March 26, 1636, it had an enrollment of 29,425 students in 2016, and employed 5,568 faculty and staff.[4] In 2011, 485 PhD degrees were awarded and 7,773 scientific articles were published. The 2013 budget of the university was €765 million.[5]

    The university is rated as the best university in the Netherlands by the Shanghai Ranking of World Universities 2013, and ranked as the 13th best university in Europe and the 52nd best university of the world.

    The university’s motto is “Sol Iustitiae Illustra Nos,” which means “Sun of Justice, shine upon us.” This motto was gleaned from a literal Latin Bible translation of Malachi 4:2. (Rutgers University, having a historical connection with Utrecht University, uses a modified version of this motto.) Utrecht University is led by the University Board, consisting of prof. dr. Bert van der Zwaan (Rector Magnificus) and Hans Amman.

Compose new post
Next post/Next comment
Previous post/Previous comment
Show/Hide comments
Go to top
Go to login
Show/Hide help
shift + esc
%d bloggers like this: