An initiative to support biomedical research through cryo-electron microscopy


A visionary project

Cryo-electron microscopy (cryo-EM) is a fundamental tool in the development of treatments for cancer, neurodegenerative disorders and other debilitating diseases. The Ecole polytechnique fédérale de Lausanne (EPFL) and the University of Lausanne (UNIL), together with the University of Geneva (UNIGE) have set up a cryo-EM imaging center to harness this technology and apply it to biomedical research. In addition, the center will be rooted in its declared ambition to advance cryo-EM technology itself, thereby distinguishing itself from other cryo-EM initiatives.

The facility is named the Dubochet Center for Imaging, after Jacques Dubochet, a Swiss researcher who played a pioneering role in developing cryo-EM technology in the 1980s – for which he shared the 2017 Nobel Prize in Chemistry with two colleagues from the US and the UK. Prof. Dubochet studied at the Ecole polytechnique de l’université de Lausanne (which became EPFL in 1969) and is currently a professor emeritus at UNIL. The Center will be managed jointly by EPFL, UNIL and UNIGE.

The power of cryo-electron microscopy

Understanding how the human body works at a molecular level is a critical step toward developing targeted, effective therapies – and cryo-EM is a powerful tool in this quest. Biomedical researchers can use this tool to explore the architecture of molecules in three dimensions at close to atomic resolution and in a near-native state.

Although first attempts to look at frozen samples were done in the 1970s, cryo-EM was born when Prof. Dubochet pioneered the method. In the early 1980s, Prof. Dubochet and his colleagues created a simple method for preparing samples so that they could stand up to the harsh vacuum conditions used in electron microscopy. The method consists of flash freezing the samples in water so that they will retain their shape without forming ice crystals. Prof. Dubochet’s groundbreaking technique led to an explosion in scientific discovery.

(Image from Wikipedia)

The Lemanic region

Lausanne and Geneva are a hotbed of biomedical research. Leading scientists at UNIL, the Lausanne University Hospital (CHUV), EPFL, the ISREC Foundation, the Ludwig Institute for Cancer Research and the University of Geneva are united in a common goal: to find treatments for life-threatening diseases. The state-of-the-art cryo-EM technology provided by the Dubochet Center for Imaging will give them a decisive advantage.

Another major advantage of locating the center in Lausanne is EPFL’s expertise in engineering, physics, chemistry, image processing and computer science – all of which underlie cryo-EM. Synergistic interactions between these disciplines and communities brought together by the center will push cryo-EM technology to new heights, and position Switzerland at the forefront of bioimaging research.

Two main objectives

The Dubochet Center for Imaging provides crucial support to biomedical research by offering state-of-the-art equipment and expertise. But it also aims to advance the technology behind cryo-EM itself: drawing on the vast technological know-how available in Lausanne, the Center contributes to the development of cryo-EM instrumentation capable of significantly outperforming current standards in terms of efficiency and resolution.

Objective 1: Contributing to biomedical research

• Neurodegenerative diseases: The Center’s equipment is used to study, with unparalleled precision, the structures of proteins involved in Parkinson's and Alzheimer's disease, and characterize the morphology of neuronal cells and brain tissue. This will help scientists understand the molecular causes and mechanisms underlying these diseases, so that they can develop effective therapeutic strategies.

• Cancer: The Center also investigates the ultrastructure of molecules that are drug targets for battling tumor growth, metastasis formation and multidrug resistance. With the help of three-dimensional structure reconstructions of proteins with bound drug molecules, scientists learn more about these drugs’ function as inhibitors in order to design better treatments. The Center also uses its cryo-EM technology to characterize the state of affected tissue in order to visualize the impact of drugs on healthy or diseased cells.

Objective 2: Taking cryo-EM technology to the next level

• Data collection: The Center will integrate innovative high-speed camera technology developed at the Paul Scherrer Institute into a modified cryo-EM instrument. This will significantly speed up data collection, reducing the time of one cryo-EM imaging session from a few days to less than one hour. The camera’s improved signal-to-noise ratio will also increase the cryo-EM instrument’s resolution.

• Image analysis: During one cryo-EM session, scientists record multiple terabytes of data containing images of millions of atomic particles of individual proteins. They then use computers to reconstruct the proteins’ three-dimensional structure in high resolution. The Center will help improve this process by developing better algorithms and by implementing a fully automated data processing pipeline that can cope with the very high speed of data collection made possible by the aforementioned camera technology.


Funding needs

EPFL, UNIL and Vaud Canton have already committed generous amounts to set up the Dubochet Center for Imaging. However, to establish a first-class research center with high international visibility, significant additional funding will be required. These additional funds will allow the Center to purchase microscopes and hire the professors and staff needed to run the Center most effectively.

The Center is thus seeking partnerships with Swiss and non-Swiss foundations and individuals who share its commitment to supporting cutting-edge biomedical research, developing the next generation of technology and training up future scientists in biomedicine, healthcare and engineering.

Prof. Jacques Dubochet, UNIL, recipient of the Nobel prize in Chemistry in 2017