From the bench to the EMBL Imaging Centre: when science meets art
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Scientists share their experiences of creating stunning images at the EMBL Imaging Centre
Many breakthroughs in science owe their discovery to images. Four centuries ago, handmade microscopes allowed Robert Hooke and Antonie van Leeuwenhoek to see a whole new miniature world through their masterfully assembled lenses. This was the start of the imaging era, which continues to flourish and bring astonishing results daily.
The EMBL Imaging Centre (IC) on the Heidelberg Campus offers scientists a place to take images to the next level. Specialists with expertise in imaging tools and techniques provide assistance and consulting, and cutting-edge instruments are available for anyone to use. Everything is in place to ensure users can make the best of their research and transform their samples into beautiful, meaningful images.
We recently spoke to some scientist visitors who have tapped EMBL IC technology and expertise. From symbiosis to drug discovery, academia and industry, these users represent the variety of scientific projects that the EMBL IC supports.
Below is a short list of their favourite words.
Learn the most common words among imaging scientists!
Light microscopy: imaging technique that uses visible light to illuminate and visualise a sample
Fluorescence microscopy: a special type of light microscopy that exploits the ability of fluorophores to emit light after excitation
Cryo-EM (cryo-electron microscopy): imaging technique applied to samples cooled to very low temperatures and frozen in different orientations
Cryo-ET (cryo-electron tomography): imaging technique that allows for the visualisation of three-dimensional models of frozen samples
A successful pilot test
Cyntha van der Berg, now a scientist at Charles River Laboratories in Leiden, was one of the EMBL IC’s first users. During her PhD in Anna Akhmanova’s lab at Utrecht University, she worked on a protein that stabilised special cellular components called microtubules. These tube-like structures support the shape of a cell, enable movement of other cellular components, and are the main engine moving cilia and flagella, the hair-like protrusions that allow a cell to move. In particular, van der Berg was investigating the localisation of her protein of interest and its role in stabilising microtubules in cilia. To do this, she needed an imaging technique that could capture high-resolution images to distinguish the position of the protein in relation to these structures. At that time, the EMBL IC Light Microscopy Team was testing a super-resolution fluorescence microscope called MINFLUX, which met her needs perfectly. As soon as she heard about it, the project was on.
“Doing experiments in a new lab, even if you have done them regularly before, requires a lot of preparation, risk calculation, and creativity on the spot. During my visit at the EMBL IC, I learned all these skills,” van der Berg recalled. “This experience also taught me the importance of clear communication, careful planning, and consideration of the priorities of everybody involved in a project.”
The data generated from this successful collaboration have been included in her first-author article, published in the Journal of Cell Biology in 2023.
From plankton to biocatalysis
The success of the first pioneering project at the EMBL IC paved the way for other enthusiastic users and their exciting research.
Johan Decelle is a group leader at the Cell and Plant Physiology Laboratory at the CEA-Grenoble and National Centre for Scientific Research (CNRS). Together with Benoit Gallet, Electron Microscopy Engineer at the Structural Biology Institute (IBS) in Grenoble, he works on symbiotic relationships between a host cell and a microalgal cell in the plankton. At the EMBL IC, they applied cryo-electron tomography (cryo-ET) – an imaging technique able to produce three-dimensional models of frozen biological samples at very low temperatures – to better understand how two cells interact with each other, and how their cellular organisation changes in symbiosis.
“The EMBL IC staff have unique expertise on cutting-edge instruments such as cryo-ET with automated microscopes. The possibility of building projects together is also unique, as is having access to different microscopes to obtain complementary results in parallel,” Decelle said. “Collaborating with the EMBL IC was an invaluable opportunity to learn through successes and failures about sample preparation, image acquisition, and analysis to improve our future research.”
The quality of the data produced with the support of the EMBL IC also meets the high standards of leading companies such as BASF, a German multinational company and the largest chemical producer in the world. At BASF, scientists use cryo-EM for research on crop protection and biocatalysis – the study of enzymes and other biological agents for chemical transformations. In the field of crop protection, researchers develop effective sustainable strategies to protect crops from pests, diseases, and environmental stresses. They also identify and characterise plant resistance mechanisms to produce resistant crop varieties. Their research on biocatalysis aims to develop novel, sustainable, and environmentally friendly biocatalysts for industrial applications.
Jeremy Sloan, BASF IP Analyst, said, “The results we achieved with the support of the EMBL IC have helped us reach important milestones for our strategic goals.” Thomas Ellinghaus, BASF Structural Biologist, added, “The exchange with the EMBL IC team about data acquisition options based on microscope choice and experimental parameters has sharpened our awareness of the relative importance of the various factors that influence how we best address our scientific questions.”
Probing deeper into viruses
Another crucial factor to consider while acquiring images of sensitive samples is safety.
Jacomine Krijnse Locker is a professor and group leader at Paul-Ehrlich-Institut. In her laboratory, she studies the poxvirus life cycle using vaccinia virus (VACV) as a model. She explained: “VACV belongs to the same family as human smallpox, a rather deadly virus now eradicated thanks to a worldwide vaccination campaign where VACV was used as a live vaccine. Despite this success, poxviruses remain a health issue, as demonstrated by the recent re-emergence of monkeypox.”
Krijnse Locker aims to dissect the VACV life cycle with imaging techniques, predominantly cryo-electron microscopy (cryo-EM) – an imaging technique applied to frozen samples at very low temperatures – and cryo-ET. She is focusing on both assembly and disassembly of the viral particles in infected cells.
VACV must be handled in strict biosafety facilities specifically designed to work with agents causing moderate human diseases. This is why Krijnse Locker partnered with the EMBL IC, where microscopes operate under the required conditions. Here, she can safely prepare samples and acquire three-dimensional images of both live and frozen infected cells.
VACV is not the only virus studied under the lenses of the EMBL IC advanced instruments. Melina Vallbracht is a postdoctoral researcher in the Chlanda Lab in the Center for Integrative Infectious Diseases Research (CIID) at Heidelberg University. She focuses on the structural characterisation of the Ebola Virus replication factory. Using in situ cryo-correlative light and electron microscopy (cryo-CLEM) and cryo-ET, she aims to structurally characterise the molecular architecture of these highly specialised, membrane-less viral structures. The crowded environment of the cell makes it challenging to identify them, but with the support of the EMBL IC, Vallbracht was able to find their precise localisation.
“The EMBL IC is an exceptional ‘playground’ for scientists offering unparalleled and rapid access to the latest imaging technologies and outstanding expertise. Many of the advanced microscopes are not only costly but also complex to operate,” Vallbracht said. “By offering personalised and professional, one-to-one training, the EMBL IC enabled me to maximise the quality, precision, and turnaround of my data and fully leverage the capabilities of these state-of-the-art technologies.”
Enabling drug discovery through structural biology
The readily available advanced equipment and the quick turnaround time ensured by the EMBL IC are also significant advantages for Novalix, a contract research organisation that partners with major pharmaceutical and biotech companies to support them in various stages of drug discovery. With roots in structural biology, Novalix has expanded its expertise over the years to encompass numerous techniques essential to drug discovery. The structural biology department specialises in the production and structural elucidation of diverse protein targets. By partnering with the EMBL IC and gaining access to cutting-edge cryo-EM technology, Novalix expanded its capabilities to determine protein structures with atomic-level precision.
“The EMBL IC highly skilled and attentive team is known for their expert support, guidance, and responsiveness to user requirements,” said Brice Murciano, a Novalix Structural Biochemist with expertise in cryo-EM and crystallography. “Having previously worked at EMBL, I can attest to the exceptional quality of data produced by their facilities.”
Denis Zeyer, Novalix CEO, added, “Collaborating with skilled professionals who are readily accessible creates a powerful synergy that drives scientific progress.”
Expanding access to imaging in Europe
An enthusiastic user community is one of the highlights of the EMBL IC. Timo Zimmermann, leader of the Light Microscopy Team at the EMBL IC, said, “Imaging is fundamental for biology across a broad range of research fields. The excellent results of users’ projects illustrate the relevance of open access to cutting-edge imaging technologies and how worthwhile it is to embed such methods in a dedicated service structure as the EMBL IC.”
Since its official opening in July 2021, the EMBL IC has promptly become a unique hub for imaging scientists across different areas of biology, supporting more than 290 projects from more than 140 research institutes and companies. “Imaging methods and technologies keep developing, and we are currently working on bringing the next round of pre-commercial instruments and workflows into service, while also starting the early development for the subsequent round,” Zimmermann said. “I am convinced that in future projects we will be able to see exciting outcomes from these novel instruments.”
Indeed, one EMBL IC core mission is to stay at the forefront of imaging workflows for life sciences.
“Our aim is to ensure we deliver cutting-edge services to a broad and diverse research community,” said Simone Mattei, leader of the Electron Microscopy Team. “To achieve this, our teams are deeply engaged in developing new technologies and methodologies tailored to address unsolved and complex biological questions. This proactive approach allows us to adapt swiftly to the evolving landscape of the imaging field while maintaining the highest standards of service and expertise.”
A key ingredient to making the most out of state-of-the-art infrastructure is benefiting from exceptional expertise.
“Our specialists provide comprehensive support, tailored to each user’s needs, covering every stage of the process – from initial consultations and experimental design to data acquisition and image analysis,” Mattei said. “Our goal is to empower researchers to perform the most advanced imaging experiments, regardless of their prior experience or access to equipment, thereby bridging the gap between cutting-edge developments and their widespread application in the field.”