Issue 101
With the advanced mobile laboratory, EMBL is taking its service offerings to new heights, bringing cutting-edge life science technologies to the field in a way never seen before.
The Kristineberg Center for Marine Research and Innovation sits near the mouth of the Gullmar fjord in Sweden. One day in early August this year, a large truck rolled up the narrow streets of the small settlement, coming to a halt only a few meters from the water. One of those most eagerly awaiting the truck’s safe arrival was biologist Niko Leisch.
“There were a couple of areas where I was not sure if the truck will actually manage to make the narrow turns,” said Leisch, who is currently the Operational Manager of EMBL’s mobile services. “I was very relieved when it finally made it.”
With a sturdy frame, expandable walls, and scientific equipment worth several million euros, the truck that arrived at Kristineberg – the EMBL Advanced Mobile Laboratory (AML) – is a unique undertaking in the history of European life science research. The AML brings cutting-edge technology directly to the field, helping researchers process biological samples immediately after collecting them, using a variety of advanced methodologies.
One of the first users of the AML at Kristineberg was Flora Vincent, Group Leader at EMBL Heidelberg. Vincent, a marine biologist and no stranger to fieldwork, is interested in exploring the complex interactions within microbial communities, especially those involving symbiosis in single-celled microorganisms.
As part of the Traversing European Coastlines (TREC expedition) – a flagship project of EMBL’s Planetary Biology Transversal Theme – Vincent has been collecting species across land-water interfaces along the European coast. A particular point of interest for Vincent’s group is diatoms, small microscopic organisms that live in the ocean and produce a large proportion of the planet’s oxygen supply.
“I use a lot of single-cell approaches, particularly single-cell sequencing,” said Vincent. “In the past, I have sometimes needed to collect water samples and then drive two hours to a hospital with a flow cytometry unit to do my single-cell sorting. Here, with the cell sorter in the AML, it makes it much easier to begin the process on the spot, with a much lower risk of sample damage.”
With the ambitious aim of sampling soil and water at 120 sites in 46 regions across Europe within two years, the TREC expedition aims to study life across all biological scales and help provide solutions to some of the most pressing global challenges of the day. Launched in March 2023, TREC brings EMBL researchers together with many partners and collaborators to investigate life at land-sea transects all along the European coast.
Also interested in symbiosis is Johan Decelle, Group Leader at CNRS in the Cell and Plant Physiology Laboratory, Grenoble and one of the collaborators for TREC. “My experience with the AML was like a scientific dream coming true,” he said. “Not only was it a unique scientific experience with cutting-edge instruments on the field, but also a memorable human adventure with experts and colleagues in the field.”
Decelle’s team also participated in previous TREC pilot expeditions in Iceland, France, and Italy, and this work was significant in helping shape the current version of the AML.
“We know little about the structural organisation of these systems, or how the host cell integrates with the photosynthesising cell or machinery at the subcellular level,” said Decelle, “These organisms can’t be easily cultured in the lab, and we wanted to explore these symbiotic relationships in their natural environment and physiological state, freezing them for 3D electron microscopy – which we can now do with some of the instruments in the AML.”
Decelle’s team is also studying symbiosis in plankton – small unicellular ocean-living organisms, especially focusing on known symbiotic associations between photosynthetic and non-photosynthetic eukaryotic cells. Similar symbiotic interactions are believed to have taken place several times during evolution, leading to the acquisition of chloroplast – a key cell organelle responsible for photosynthesis – in lineages of plants and photosynthetic algae.
According to Vincent, the AML also provides researchers an opportunity to think creatively, with tools now being available on the field that were never possible before. “It’s pushing us to think about a field sampling in a different way,” she said. “It really enables me to draw new paths in my brain, ones that I could have never thought of as possible in the natural environment. It also gives us the opportunity to combine the best of two worlds by using the AML tools on samples collected by the Tara schooner. In a single day, we can get a full picture of the marine microbiome thanks to the Tara holistic sampling strategy, and then leverage the AML to conduct state-of-the-art molecular and cellular analyses on targeted species”
This is particularly suited to Vincent’s team, who use an adaptive sampling approach where the research strategy is tailored to the collection of living organisms that each sample contains, rather than vice versa.
“The challenge is that we are really building the plane as we fly it,” said Vincent. “A lot of the machines are on the field for the first time. Each of those machines can be used in a standalone manner, but where I have a lot of fun is building connections between those tools.”
Using these tools and creating such new symbiotic relationships between methodologies and scientific approaches, the researchers hope to arrive at new insights that could help address some of the most pressing global challenges we face today – climate change, environmental degradation, and biodiversity loss.
Another researcher interested in exploring plankton communities is Omaya Dudin, group leader at the Swiss Federal Institute of Technology Lausanne (EPFL). Dudin’s lab explores the evolutionary origins of animal development and is part of the expansion microscopy (PlanExM) team that, as part of TREC, is trying to create an atlas of plankton biodiversity along European coasts. They hope to create a snapshot that would be crucial in assessing the impact of climate change on these populations in the future.
“The biggest problem that happens in environmental sampling is that the moment you go beyond an hour or two from the time of sampling, you’re not really sure what you’re looking at any more,” said Dudin.
This is because many of the plankton living in coastal waters tend to die quickly when taken out of their native environment, greatly altering the species composition of the sample depending on how much time has passed since collection.
The ability of the AML to travel very close to sampling locations allows Dudin and his team to expedite these crucial sample preservation steps and image plankton at the sub-cellular resolution using expansion and electron microscopy. It is also critical for the second part of the team’s work, which focuses on culturing some of the species collected from the environment in order to potentially bring them back to the lab to study.
“EMBL is very well known for having high-end techniques in microscopy and molecular biology, and to bring them here, to a place where the samples are fresh, is something very unique,” said Rainer Pepperkok, Director of Scientific Core Facilities and Services at EMBL. “This is something that I think will set the basis, for many decades, of functional and mechanistic research that integrates these different domains – the sea and the land – and to understand how these molecular ecosystems are functioning.”
Arriving in Kristineberg just a day or two after the AML, Dudin was excited to be able to finally use the mobile laboratories. “It’s almost like an extension of my own lab,” he said. “The quality of the equipment is beyond imagining and it’s so well-organised, it just feels like home.”
With the help of the AML, the PlanExM team can collect samples using specially designed ‘plankton nets’, bring them to the laboratory on wheels, and ‘fix’ them in three different ways in less than an hour. These methods include using chemical fixatives, high-pressure freezing, and plunge freezing, the latter two allowing researchers to use these samples for electron microscopy. Similarly, for culturing new species, the team is going to be able to combine the speed at which the samples are brought to the mobile lab with the single-cell sorter present on board to potentially get single-cell cultures, something still uncommon in plankton research.
“I think it’s going to change the perspective on how we do certain kinds of research,” said Dudin. “Right now, almost everyone wants to work on model systems because there are clear protocols, images, and tools. And for many of these wild species, no one’s been working on them simply because they are so difficult to catch – by the time they reach the lab, they are dead. With the AML and with this mission, we are going to keep getting better at collecting data on these understudied organisms and potentially give hope to researchers who want to work on these. In that sense, I think it’s going to be a game changer.”
One of the key challenges in working with environmental samples when compared with model organisms in the laboratory is the sheer heterogeneity – samples can contain thousands of diverse species and finding the ones you are particularly interested in can be a herculean task.
The TREC team led by Yannick Schwab, Team Leader and Head of the Electron Microscopy Core Facility at EMBL, is trying to solve this problem. “My team is interested in developing methods that enable researchers to target electron microscope imaging to specific cells in complex and highly heterogenous specimens,” said Schwab.
One of the projects Schwab is leading focuses on dinoflagellates, a very rich and diverse group of plankton. When trying to zoom in on specific dinoflagellate groups in environmental samples, researchers need to perform multimodal correlative imaging – where the same sample is studied via different advanced imaging methods and the results are combined to yield a ‘big picture’ view. However, to preserve the ultrastructure of these organisms, state-of-the-art cryo-fixation methods are needed, and these sample preparation steps can only be performed with dedicated machines like a high-pressure freezer or a plunge freezer. As Dudin also noted, it’s very unusual for such machines to be available at or near field locations.
“When we are collecting non-cultivable dinoflagellates in the field, we need to rush to fix them before they start being denatured. Therefore, we must deploy those instruments for cryo-fixation as close as possible to the sampling; by doing so, we literally freeze our samples on the beach,” said Schwab. “This would simply not be possible without the AML.”
In a recent publication, a team led by Schwab and Paolo Ronchi from EMBL Heidelberg demonstrates a new method that uses correlative light and electron microscopy to help us accurately identify plankton species collected in the field. The researchers plan to apply this technique to samples from the TREC expedition, with the help of the AML.
However, as Schwab points out, it is not only the advanced instruments that are important here, but also the dedicated team that enables their use by offering their expertise. In addition to Leisch, the EMBL mobile services team currently includes Michael Bonadonna – specialist in flow cytometry and cell sorting, Tina Wiegand – specialist in fluorescence microscopy, and Paulina Cherek – specialist in electron microscopy sample preparation.
Along with the AML, the mobile services team also helped outfit vehicles that can access different terrains of the sampling sites to support on-site sample collection and a sampling van equipped for sample processing and storage.
Leisch, along with Schwab, Pepperkok, and Paola Bertucci (Head of EMBL Scientific Expeditions), has spent over a year helping develop and deploy the advanced mobile lab, working with the Toutenkamion Group, a French industrial mobility company. “The process was surprisingly smooth,” said Leisch. “For every single machine, we came up with a way of making sure we can install it in the truck in such a way that it can be used to its full potential on site, but can also be easily secured during moving. This ensures we can quickly get to work once we arrive at a site. We also brainstormed potential challenges that may arise once on the road and tried to find solutions.”
The process involved many custom-made setups and coordination with multiple scientific instrumentation providers. However, the effort paid off and in August 2023, the AML saw its first full deployment in Kristineberg.
“On a personal note, it was a great pleasure to work with Franck Neveu and Melanie Asselin from the Toutenkamion Group,” added Leisch. “The two of them were our contacts on the industry side and halfway through the project, they became as invested as we were in seeing the unit delivered in the best possible way.”
The TREC expedition is going to continue till mid-2024, but AML’s story does not end there. “We are right now working on making the AML available as a service unit,” said Leisch. “Everyone from individual researchers to consortia or even nations can then ask for and request the services, and then we together with the team would come to provide those on site.”
Researchers from EMBL member states agree. “Bringing a truck like this on the international scene will allow us to go to places that no one has gone before,” said Dudin. “And that opens up possibilities that never existed before.”
In the meantime, the AML will make its way to the next few TREC supersites, where it will continue to inspire intellectual curiosity and collaboration.
“One evening, we observed the unicellular organism Noctiluca in our samples. Like its name suggests (‘Noctiluca’ translates to ‘light at night’) it is often responsible for the well-known phenomenon of bioluminescence.” recalled Leisch. “Everyone got excited and we set up an impromptu midnight sampling in order to collect more of these microbes in the night. It was past midnight and the whole place was buzzing with enthusiasm and excitement and scientific curiosity. And it was just so beautiful to see that and be able to experience that with my colleagues.”
EMBL acknowledges the generous support of many institutions, donors and sponsors, in particular the Manfred Lautenschläger Foundation, as well as Eppendorf SE, and Carl Zeiss Microscopy, in helping make the AML possible. We also thank Thermo Fisher Scientific and Ted Pella, Inc. for donating scientific instruments for the AML.
The EMBL agreement, which made reality the idea of creating a European laboratory for life sciences, was signed in 1973 and ratified in 1974. Fifty years later, we look back at this historic moment.
Baubak Bajoghli, Director of Austrian Bioimaging/CMI, discusses his passion for imaging and his work straddling basic and applied research in biology.
Click here to download a quick overview of all the articles included in this digital issue of EMBLetc.