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)

20.07.21
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

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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.

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“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 .

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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.

Organization

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
Networking
Programming Languages & Formal Methods
Security & Cryptography
Signal & Image Processing
Systems

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