{"id":53290,"date":"2022-11-16T12:00:00","date_gmt":"2022-11-16T11:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?post_type=embletc-issue&p=53290"},"modified":"2022-11-17T11:34:48","modified_gmt":"2022-11-17T10:34:48","slug":"issue-99","status":"publish","type":"embletc-issue","link":"https:\/\/www.embl.org\/news\/embletc\/issue-99\/","title":{"rendered":"Issue 99"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":0,"parent":0,"menu_order":0,"template":"","class_list":["post-53290","embletc-issue","type-embletc-issue","status-publish","hentry"],"acf":{"embletc_main_stories":[{"ID":53292,"post_author":"124","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"\n

The minimal cell<\/h2>\n\n\n\n

In 1944, researchers from California\u2019s Department of Public Health managed to isolate the causative agent for atypical pneumonia, a respiratory illness that afflicted many military personnel during World War II. First called the \u2018Eaton Agent\u2019 after the researcher who isolated it, the pathogen was believed for many years to be an unidentified virus. It was not until the 1960s that scientists determined conclusively that the infectious agent causing atypical pneumonia was not a virus, but a very small bacterium.  <\/p>\n\n\n\n

Mycoplasma pneumoniae, <\/em>as the species was later named, is among the tiniest free-living microorganisms on Earth. Its genome contains only 687 genes. For comparison, Escherichia coli<\/em>, the bacteria most commonly used in lab studies, has over 4,400 genes, while human beings have over 20,000. At less than 1 micron in length, 1.5 trillion M. pneumoniae<\/em> could fit into a single droplet of water. When it infects humans, it parasitises respiratory tract cells, often evading the immune system during the process. Also, unusual for bacteria, it lacks a cell wall surrounding its plasma membrane. <\/p>\n\n\n\n

A group of EMBL scientists is now using this unique organism to interrogate fundamental processes that underlie the biology of a living cell. Spearheaded by the research group of Julia Mahamid<\/a>, and enabled by collaborations with multiple groups within and outside EMBL, the researchers are attempting to 'see', at unprecedented resolution, the mechanisms of life inside one of the smallest living cells.\u00a0\u00a0<\/p>\n\n\n\n

From pathogen to model<\/strong><\/h2>\n\n\n\n

Researchers from EMBL\u2019s Structural and Computational Biology unit established Mycoplasma pneumoniae <\/em>as a model organism in the early 2000s. Teams led by Peer Bork<\/a>, Luis Serrano<\/a>, and Anne-Claude Gavin<\/a> sequenced and annotated its genome, which was followed by the publication of three seminal papers delineating its metabolomics, proteomics, and transcriptomics, respectively.\u00a0<\/p>\n\n\n\n

Two decades earlier, Jacques Dubochet<\/a>, another EMBL researcher, had developed a way to prepare and image biological samples using cryo-electron microscopy (cryo-EM), work that won him the Nobel Prize in 2017. Relying on a method of freezing biological samples extremely quickly to prevent the formation of ice crystals, cryo-EM allows researchers to observe the structure of complex biomolecules at atomic resolution.\u00a0<\/p>\n\n\n\n

Soon afterwards, researchers developed the technique of cryo-electron tomography (cryo-ET), another big leap in harnessing the power of electron microscopy. While cryo-EM allows scientists to observe the structure of biological molecules, it usually requires samples of carefully isolated molecules taken out of their cellular context. However, cryo-ET allows scientists to take snapshots of intact cells, along with all their internal components, which can later be reconstructed in 3D. <\/p>\n\n\n\n

Given Mycoplasma\u2019s <\/em>small size, it is possible to obtain a series of images to combine into a clear picture of the entire cell and all its constituents. When Mahamid started her group at EMBL in 2017, she decided to harness the growing power and resolution of advanced cryo-ET technologies to study cellular mechanisms in action inside this model organism.<\/p>\n\n\n\n

\u201cPersonally, I'm amazed by the ability to do structural biology inside cells,\u201d said Joe Dobbs, one of the PhD students in the Mahamid group. \u201cCryo-EM is well-known for its ability to provide insight into the structures of macromolecular complexes in purified samples, but actually seeing the insides of cells, and how molecules interact with each other in context, is incredible.\u201d<\/p>\n\n\n\n

\"Female
Julia Mahamid, Group Leader in the Structural and Computational Biology Unit, EMBL Heidelberg, in front of a Titan Krios cryo-electron microscope. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

Connecting biology across scales<\/strong><\/h2>\n\n\n\n

The study has attracted a diverse group of scientists and engineers. Vastly differing in areas of interest and expertise, they are united by their belief in the potential for M. pneumoniae <\/em>to serve as a window into the life of a cell. <\/p>\n\n\n\n

For example, Judith Zaugg<\/a> started her lab at EMBL in 2014 and is interested in understanding the molecular basis of complex genetic traits and diseases, for which she usually works with human genomics data. With Mycoplasma, <\/em>she became fascinated by the idea of observing gene expression in action within a living cell. In the cryo-ET images that the Mahamid group grabs, DNA can be observed as filamentous structures and the RNA polymerase enzymes seen attached to them, and Zaugg believes that one day this might be used to figure out which regions of DNA or genes are active \u2013 or being \u2018transcribed\u2019 \u2013 at a given point in time.\u00a0<\/p>\n\n\n\n

\u201cIt is very exciting to \u2018see\u2019 transcription in progress,\u201d said Zaugg. \u201cWith this model, we can perhaps one day address very fundamental biological questions like \u2013 how does the cell reorganise its DNA upon receiving a certain stimulus? While we know (based on genomics data) that genes are differentially expressed based on stimuli, we still don't know how the cell rearranges its internal structure and genome to achieve this.\u201d  <\/p>\n\n\n\n

\"Two
Judith Zaugg, Group Leader in the Structural and Computational Biology Unit, EMBL Heidelberg, and Frosina Stojanovska, PhD student in the Zaugg lab, looking at a computationally annotated M. pneumoniae tomogram. Credit: Stuart Ingham\/EMBL<\/figcaption><\/figure>\n\n\n\n

With future advances in correlative electron and fluorescence microscopy, Zaugg hopes that answering questions like these might become possible. In turn, her team brings to the project computational expertise to mine the data, which otherwise could have taken months or even years to process.<\/p>\n\n\n\n

Peer Bork<\/a>, who co-initiated and coordinated the initial proteomic, transcriptomic, and metabolomic characterisation of M. pneumoniae <\/em>in the 2000s, is interested not only in the infectious disease aspects of this model system but also in its potential for understanding molecular networks. His group has aided the study with computational expertise as well as by connecting global bioinformatic data.\u00a0<\/p>\n\n\n\n

\u201dThis project leverages some of EMBL\u2019s key strengths \u2013 collaborating and coordinating across a diversity of disciplines to answer fundamental biological questions that cannot be addressed otherwise,\u201d said Bork. <\/p>\n\n\n\n

Maria Zimmermann-Kogadeeva<\/a>, another EMBL group leader, started collaborating with Mahamid while still a postdoc in the Bork group. Her computational insights played a key role in a recent project that studied the machinery of protein synthesis in action inside the cell. She is also involved in a project focused on studying previously uncharacterised membrane proteins that can be observed in cryo-ET images of Mycoplasma.\u00a0<\/em><\/p>\n\n\n\n

\u201c<\/em>The cryo-ET technology allows us to look deep inside the cell, and understand how intracellular processes change under different conditions,\u201d said Zimmermann-Kogadeeva. \u201cThe data obtained is of very high quality and can be combined with other molecular datasets to ask interesting questions.\u201d She and Bork are both optimistic about the potential of investigating cellular metabolomics within Mycoplasma<\/em> in the future. <\/p>\n\n\n\n

\u201cOur goal is to connect biology across scales,\u201d said Mahamid. \u201cMycoplasma <\/em>gives us a way to study biological systems all the way across from the nanometre range of molecules to the micrometre range of entire cells.\u201d <\/p>\n\n\n\n

New tools for new insights<\/strong><\/h2>\n\n\n\n

While cryo-ET allows scientists to look at the whole cell, it doesn\u2019t make it easy to identify what<\/em> they are seeing. Unlike with fluorescence microscopy,  it isn't easy to tag or label specific objects inside the cell and distinguish them from their neighbours in cryo-ET. As a result, scientists are effectively left with an incomplete map, most of which has no helpful labels. <\/p>\n\n\n\n

Soheil Mojiri, a postdoctoral fellow in the Ries group<\/a>, is building a microscope to solve this problem. An engineer by training, Mojiri is fascinated by the possibility of exploiting optical physics to address challenging biological questions. His goal is to fruitfully marry cryo-ET and super-resolution optical microscopy at low temperatures.\u00a0<\/p>\n\n\n\n

\"Two
Jonas Ries, Group Leader in the Cell Biology and Biophysics Unit, EMBL Heidelberg and Soheil Mojiri, postdoc in the Ries group, in front of Mojiri\u2019s prototype cryo-single molecule localisation microscope (cryo-SMLM). Credit: Stuart Ingham\/EMBL<\/figcaption><\/figure>\n\n\n\n

\u201cCryo-ET allows us to look at molecular architecture and molecules in context, but we're limited by what we can identify in the extremely noisy, crowded, and heterogeneous cellular environment. So while we can just about make out big things, such as ribosomes - the cell's protein production machines, smaller molecules and complexes can escape our notice unless we have prior information to use,\u201d said Mojiri. <\/p>\n\n\n\n

Mojiri is developing a prototype microscope that would allow scientists to take a frozen cell sample, visualise individual proteins or complexes with fluorescent tags that are genetically introduced into live cells, and later subject the same sample to cryo-ET. Comparing the images obtained by the two methods would let researchers leverage electron microscopy\u2019s structural resolution as well as fluorescence microscopy\u2019s specificity. <\/p>\n\n\n\n

Not all technology development for this project is on the hardware side, however. The researchers have generated a huge volume of data, which presents challenges in analysing it to draw new insights. This is where Anna Kreshuk<\/a>, with her expertise in machine-learning-based image analysis, steps in. Kreshuk and her team create innovative AI-based methods that find meaningful information from biological images, often gigabytes in size and containing a lot of background information that may not be relevant.\u00a0<\/p>\n\n\n\n

\"Three
Anna Kreshuk (centre), Group Leader in the Cell Biology and Biophysics Unit, with Jonas Ries (right) and Julia Mahamid (left). Credit: Jervis Thevathasan \/ EMBL <\/figcaption><\/figure>\n\n\n\n

Ricardo Sanchez, an ARISE fellow<\/a> at EMBL Heidelberg, has been working on finding ways around this challenge. \u201cWith cryo-ET, one of the biggest problems is reducing the signal-to-noise ratio and identifying structures of interest among all the cellular background,\u201d he said. \u201cMy goal is to solve this problem with the least amount of computational resources.\u201d<\/p>\n\n\n\n

\u201cWhat fascinates me is the completeness of this system,\u201d said Kreshuk. \u201cIt's the whole living thing. Everything that it needs to be an independent (and pretty dangerous) living organism is visible in that one image.\u201d<\/p>\n\n\n\n

Putting together a cellular picture<\/strong><\/h2>\n\n\n\n
\"The
Using cryo-ET, researchers can look at small bacteria in progressively higher resolutions, ultimately resolving the structure of molecular machines, such as ribosomes. From left to right, this graphic shows M. pneumoniae <\/em>cells being placed on a grid for cryo-electron microscopy, a cryo-ET slice of the cell with ribosomes marked in green, and the resolved structure of an individual ribosome derived from such an image. In the background, we can see M. pneumoniae cells, as seen using scanning electron microscopy. Credit: Isabel Romero Calvo \/EMBL<\/figcaption><\/figure>\n\n\n\n

The project is already yielding dividends when it comes to understanding fundamental biological processes that make life possible. In a recently published paper, Liang Xue from the Mahamid group led a study that allowed the team to visualise the process of translation \u2013 the synthesis of new proteins \u2013 inside the cell at atomic detail. The structures they focused on is probably one of the easiest to identify in a cryo-ET image \u2013 ribosomes. Ribosomes are some of the most ancient molecular machines present in all living organisms and essential for protein synthesis. <\/p>\n\n\n\n

\u201cRibosomes not only play an essential role in genetic information flow but also serve as platforms to monitor cellular states, e.g. cell stress response,\u201d said Xue. \u201cInside living cells, ribosomes function as highly interconnected networks of molecular machines.\u201d <\/p>\n\n\n\n

Using high-quality cryo-ET Mycoplasma <\/em>data, <\/em>the researchers were not only able to observe the dynamic structural changes that took place in ribosomes as they proceeded through the protein synthesis cycle, but they could also observe what happens to these processes when antibiotics perturb cells. Since the translation machinery is quite similar in structure and function throughout the tree of life, the study can be extrapolated to other prokaryotic or eukaryotic species that are more challenging to image with cryo-ET. <\/p>\n\n\n\n

\"Two
Liang Xue, postdoc, and Joe Dobbs, PhD student in the Mahamid group, at the Titan Krios electron microscope controls. Julia Mahamid and Rasmus Kjeldsen Jensen can be seen in the background. Credit: Stuart Ingham\/EMBL<\/figcaption><\/figure>\n\n\n\n

\u201cI hope my work at EMBL establishes a framework<\/a> to do high-resolution<\/a> structural biology inside the cell,\u201d said Xue. \u201cRibosomes and Mycoplasma<\/em> are just the beginning. With more and more molecular machines resolved inside cells, we are heading toward the ultimate goal of building an atomic cell model.\u201d<\/p>\n\n\n\n

Collaborating to make progress<\/strong><\/h2>\n\n\n\n

The researchers are also using Mycoplasma <\/em>to understand the role of unknown membrane proteins that can be observed in cryo-ET images In these studies, Jan Kosinski<\/a>\u2019s and Christian L\u00f6w<\/a>\u2019s groups at EMBL Hamburg and Nassos Typas<\/a>\u2019s group at EMBL Heidelberg are also involved. A tool they have turned to often in these investigations is AlphaFold<\/a>, the AI algorithm that predicts protein structures, whose developers won the 2023 Breakthrough Prize in life sciences.\u00a0<\/p>\n\n\n\n

The project also involves collaborations with scientists outside EMBL and in EMBL member states, including the groups of J\u00f6rg St\u00fclke<\/a>, Georg-August-Universit\u00e4t G\u00f6ttingen, Patrick Cramer<\/a>, Max Planck Institute for Multidisciplinary Sciences, Juri Rappsilber<\/a>, Institut f\u00fcr Biotechnologie, Technische Universit\u00e4t Berlin, and Luis Serrano<\/a>, Centre for Genomic Regulation, Barcelona.<\/p>\n\n\n\n

While research in the last few decades has helped to rapidly identify and annotate many species\u2019 genomes, our knowledge of the function and precise roles of most genes and proteins remains incomplete, even for an organism as simple as Mycoplasma<\/em>. Projects like these are a key step towards bridging this knowledge gap. EMBL\u2019s new programme \u2018Molecules to Ecosystems\u2019<\/a> aims to study living organisms in the context of their environment. In doing so, scientists will doubtless encounter many more new molecules and biological processes, which this project paves the way towards studying and understanding in detail. It also exemplifies the collaborative approaches at the heart of this new programme.<\/p>\n\n\n\n

\"A
Rasmus Kjeldsen Jensen, postdoc in the Mahamid group, working in the lab. Credit: Stuart Ingham\/EMBL<\/figcaption><\/figure>\n\n\n\n

\u201cI think it is a pretty long and hard way from imaging Mycoplasma<\/em> to the data interpretation. We need diverse expertise and knowledge to pave this way,\u201d said Mojiri. \u201cIn particular, we require biologists, physicists, and data scientists.\u201d The collaborative atmosphere at EMBL has made such a coming together of talents and knowledge possible. The team gathers in a monthly meeting dedicated to the Mycoplasma<\/em> project to exchange ideas, discuss the progress of experiments, and troubleshoot challenges.<\/p>\n\n\n\n


\u201cMycoplasma <\/em>has turned out to be a powerful model for studying the dynamics of molecular machines and understanding intracellular cross-talk,\u201d said Mahamid. \u201cThe collaborative approach was absolutely crucial to this. To realise the massive potential of cryo-ET and the Mycoplasma <\/em>model, we will need to continue as we have started, together and moving forward.\u201d<\/p>\n","post_title":"Uncovering a microbe\u2019s inner life","post_excerpt":"Researchers have observed the inner workings of an unusual bacteria at an unprecedented level of detail.","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"uncovering-a-microbes-inner-life","to_ping":"","pinged":"","post_modified":"2022-11-16 14:36:13","post_modified_gmt":"2022-11-16 13:36:13","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=53292","menu_order":0,"post_type":"embletc","post_mime_type":"","comment_count":"0","filter":"raw"}],"embletc_main_story_subheading":"

Researchers have observed the inner workings of an unusual bacteria at an unprecedented level of detail<\/p>\n","embletc_main_story_teaser":"

Mycoplasma pneumoniae<\/em> is among the smallest free-living microorganisms on Earth. A group of scientists at EMBL now use this unique organism to interrogate the fundamental processes that underlie the biology of a living cell.<\/p>\n","embletc_main_story_image":{"ID":53944,"id":53944,"title":"PrimaryComposition_Final_1000x600","filename":"PrimaryComposition_Final_1000x600.jpg","filesize":712769,"url":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/PrimaryComposition_Final_1000x600.jpg","link":"https:\/\/www.embl.org\/news\/embletc\/issue-99\/attachment\/primarycomposition_final_1000x600\/","alt":"","author":"124","description":"","caption":"","name":"primarycomposition_final_1000x600","status":"inherit","uploaded_to":53290,"date":"2022-11-03 15:04:42","modified":"2022-11-03 15:04:42","menu_order":0,"mime_type":"image\/jpeg","type":"image","subtype":"jpeg","icon":"https:\/\/www.embl.org\/news\/wp-includes\/images\/media\/default.png","width":1000,"height":600,"sizes":{"thumbnail":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/PrimaryComposition_Final_1000x600-150x150.jpg","thumbnail-width":150,"thumbnail-height":150,"medium":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/PrimaryComposition_Final_1000x600-300x180.jpg","medium-width":300,"medium-height":180,"medium_large":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/PrimaryComposition_Final_1000x600-768x461.jpg","medium_large-width":768,"medium_large-height":461,"large":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/PrimaryComposition_Final_1000x600.jpg","large-width":1000,"large-height":600}},"embletc_main_story_hero":{"ID":53632,"id":53632,"title":"EMBLetcBanner","filename":"EMBLetcBanner-scaled.jpg","filesize":176953,"url":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/EMBLetcBanner-scaled.jpg","link":"https:\/\/www.embl.org\/news\/embletc\/issue-99\/attachment\/embletcbanner\/","alt":"Hero image featuring mycoplasma ribosomes","author":"124","description":"","caption":"","name":"embletcbanner","status":"inherit","uploaded_to":53290,"date":"2022-11-02 10:47:39","modified":"2022-11-02 10:48:03","menu_order":0,"mime_type":"image\/jpeg","type":"image","subtype":"jpeg","icon":"https:\/\/www.embl.org\/news\/wp-includes\/images\/media\/default.png","width":2560,"height":853,"sizes":{"thumbnail":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/EMBLetcBanner-150x150.jpg","thumbnail-width":150,"thumbnail-height":150,"medium":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/EMBLetcBanner-300x100.jpg","medium-width":300,"medium-height":100,"medium_large":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/EMBLetcBanner-768x256.jpg","medium_large-width":768,"medium_large-height":256,"large":"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/EMBLetcBanner-1024x341.jpg","large-width":1024,"large-height":341}},"embletc_other_stories":[{"ID":53294,"post_author":"124","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"\n

When a team of EMBL biologists decided to conduct an expedition to Iceland earlier this year to collect environmental samples from its coast, a volcano was not really in the plan. But when Fagradalsfjall, located 60 km from Reykjavik, erupted only five days before the expedition, it added a little bit of otherworldliness to a trip which had already been pushing at the boundaries of \u2018traditional\u2019 fieldwork.  <\/p>\n\n\n\n

\"Photograph
The Fagradalsfjall volcano erupted on 3 August 2022, five days before the expedition was due to start. Many of the expedition members made the short trip froom their sampling location to the volcanic site for a once-in-a-lifetime experience. Credit: Niko Leisch\/EMBL<\/figcaption><\/figure>\n\n\n\n

\u201cIt was absolutely breathtaking,\u201d recalls Joanna Zukowska, a scientist in the Pepperkok team<\/a> at EMBL Heidelberg. \u201cI was speechless.\u201d<\/p>\n\n\n\n

The expedition was the final pilot for Traversing European Coastlines (TREC)<\/a>, a flagship project of the new EMBL programme that aims to study life in context. TREC is a way to bring together environmental research and molecular and cellular biology to address urgent societal challenges.<\/p>\n\n\n\n

Over a period of three weeks in August 2022, EMBL researchers and their collaborators visited three different locations in Iceland \u2013 Reykjavik, Westfjords, and Akureyri \u2013 with unique climatic and environmental conditions. They collected marine organisms, soil, seawater, and sediments, and tested out experimental protocols that would become critical for the large-scale expedition that EMBL will run in 2023 and 2024 for the TREC project. <\/p>\n\n\n\n

\"Map
Map of Iceland showing the chief sampling sites. The three primary locations are shown in orange, and secondary sites in black. Credit: Kiley Seitz\/EMBL, Map data: Google Earth \u00a9<\/strong>2022. <\/figcaption><\/figure>\n\n\n\n

This pilot expedition was co-organised by the Icelandic biodiversity research network BIODICE. It involved collaborations with host institutions across Iceland, including the Marine and Freshwater Research Institute (MFRI) and the University of Iceland. <\/p>\n\n\n\n

Skimming for Plankton<\/strong><\/h2>\n\n\n\n

Reykjavik is the capital of Iceland and home to the Marine and Freshwater Research Institute (MFRI)<\/a>. This institute was the first stop for the EMBL researchers and their collaborators for this pilot expedition. The visit was supported by MFRI\u2019s director \u00deorsteinn Sigur\u00f0sson and marine geneticist Christophe Pampoulie.<\/p>\n\n\n\n

Preparations began last year when EMBL scientists visited Iceland to engage with the local scientific community, visit institutes, and check out sampling locations.  This summer, the TREC team shipped scientific equipment, labware, and reagents to MFRI, a vast logistics effort coordinated by Cristian Tambley, Valerie Maier, Niko Leisch, and Paola Bertucci at EMBL.<\/p>\n\n\n\n

The sample-collecting teams soon followed. <\/p>\n\n\n\n

\"A
EMBL Team Leader Yannick Schwab holding up a plankton net. Credit: \u00a9Kristinn Ingvarsson\/University of Iceland<\/figcaption><\/figure>\n\n\n\n

Once at the site, the teams quickly settled into a routine. Every morning began with climbing into a boat and heading out to the ocean. Once a safe distance from shore, a plankton net \u2013 a specially constructed cone-shaped net with an extremely fine mesh \u2013 was thrown overboard and dragged behind the boat for a few minutes. This allowed enough time for it to fill with tiny unicellular sea creatures called plankton, which the team then filtered and carried back to shore. Once back at MFRI\u2019s labs, the teams went to work, studying and preserving the plankton in various ways.<\/p>\n\n\n\n

\u201cPlanktons fill the oceans and seas around us and yet we know so little about them,\u201d said Omaya Dudin<\/a>, group leader at the Swiss Federal Institute of Technology Lausanne (EPFL) and one of the members of the expedition. \u201cThey're extremely important for the oxygenation of the planet, for the food chain in the sea, and for the climate and the environment.\u201d<\/p>\n\n\n\n

\"Photograph
The boat which carried researchers to plankton sampling sites each morning. Credit: Hiral Shah\/EMBL <\/figcaption><\/figure>\n\n\n\n

Dudin\u2019s lab specialises in understanding the origin of animal development using expansion microscopy, a technique which they share with their collaborators \u2013  Gautam Dey<\/a>, Sinem Saka<\/a>, and Yannick Schwab<\/a> at EMBL Heidelberg and Marine Laporte, Paul Guichard, and Virginie Hamel at the University of Geneva. When an opportunity to join the TREC expeditions came up, the \u2018Expansion Team\u2019 felt it was too good an opportunity to lose. <\/p>\n\n\n\n

Expansion microscopy involves embedding biological samples in a gel matrix, and then slowly expanding the gel. The embedded cells get \u2018blown up\u2019 along with the gel, allowing scientists to glimpse details that would ordinarily have been beyond the resolution of light microscopy. It also allows better permeability for stains and antibodies, helping researchers identify structures, proteins, and molecular complexes inside the cells. <\/p>\n\n\n\n

In spite of its remarkable strengths and potential, expansion microscopy is not a technique routinely tested in the field. Members of the Expansion microscopy team who travelled to Iceland worked on standardising its protocols to observe plankton samples freshly obtained from the sea. <\/p>\n\n\n\n

\"Two
Johanna Zukowska and Karel Mocear filtering collected plankton samples on the expedition boat. Credit: Hugo Berthelot\/EMBL<\/figcaption><\/figure>\n\n\n\n

The expansion team had two goals: to create a biobank and to build an atlas of plankton images. The biobank \u2013 a catalogue of plankton species that can serve as a baseline biodiversity snapshot \u2013 would allow scientists to identify potential future changes as oceans warm over the coming years. The atlas \u2013 a collection of images grabbed by expansion microscopy of marine plankton species \u2013 would also act as an invaluable resource for future biologists. <\/p>\n\n\n\n

\u201cThere are about 10 million species estimated to live on this planet. Out of these, we have only identified or characterised about two million using genomics,\u201d said Dudin. \u201cAnd out of these millions, there are only 50 model organisms from which we have learned almost all the biology that we know today.\u201d<\/p>\n\n\n\n

Characterising and measuring the biodiversity of our shallow oceans and coastal ecosystems would be the first step towards building up a complete picture of the networks that sustain life in these incredibly vulnerable environments. <\/p>\n\n\n\n

\"A
The team that collected and processed planktons at Reykjavik. Credit: TREC Team.<\/figcaption><\/figure>\n\n\n\n

Going after invertebrates<\/strong><\/h2>\n\n\n\n

Biodiversity exists at many scales, however, and not all the creatures the biologists sought at Iceland were microscopic. Leslie Pan and Emily Savage joined the expedition representing the Arendt group<\/a> at EMBL Heidelberg and their interests lie in a small marine ragworm called Platynereis dumerilii. <\/em><\/p>\n\n\n\n

\"An
An immature Platynereis worm. Credit: Emily Savage\/EMBL<\/figcaption><\/figure>\n\n\n\n

The life cycle of Platynereis dumerilii<\/em> is linked closely to the lunar cycle. After emerging as larvae, the worms swim around in the sea until they grow large enough to \u2018settle\u2019. During this next stage, they build long tubes that attach to sea algae and rocks and live inside them until they mature. The final step takes place during new moon nights, when the mature individuals swim to the surface of the sea to mate and spawn the next generation. <\/p>\n\n\n\n

For biologists, the fascination for Platynereis dumerilli <\/em>lies in the fact that it is extremely slow evolving \u2013 it is believed to have changed little genetically and phenotypically in the last several million years. This, in turn, makes it an ideal candidate to study the evolution and emergence of the central nervous system. While it has been cultured in the lab since 1953, studying it directly in its natural environment presents many interesting opportunities. <\/p>\n\n\n\n

\"A
Emily Savage examining algae for the presence of Platynereis. Credit: Leslie Pan\/EMBL<\/figcaption><\/figure>\n\n\n\n

For the Arendt team, their days during the expedition started with loading equipment into a van and driving out to the predetermined coastal sites in Reykjavik and the Westfjords. Once there, expert divers retrieved clumps of algae from shallow sea floors. On the beach, Pan and Savage set up workstations with wide trays, where they spent the next few hours sorting through algae, searching for evidence of hidden tubes and worms within. <\/p>\n\n\n\n

While the team found no evidence of P. dumerilii <\/em>in the waters on this trip, many other invertebrate species were present. During the main TREC expedition, beginning in 2023, the team are confident to find the worms. \u201cWe plan to look at their population genetics in relation to the surrounding environmental factors, like the temperature or salinity of the seawater,\u201d said Pan. \u201cWe would like to see whether such factors have given rise to distinct genotypes and whether the genotypes, in turn, have helped them adapt better to their surroundings.\u201d<\/p>\n\n\n\n

\"Small
Planarians adhering to the surface of a rock. Credit: Hanh Vu\/EMBL<\/figcaption><\/figure>\n\n\n\n

Hanh Vu<\/a>, who joined EMBL Heidelberg as a group leader in 2021, is fascinated by another class of worms \u2013 planarians. Planarians are free-living flatworms that have almost unlimited regenerative capacity, and depending on the habitat and species, range in length from just a few millimetres to over a metre. Vu\u2019s lab studies different species of planarians to figure out how and why animals regulate their body size. <\/p>\n\n\n\n

Just like with Platynereis, <\/em>environmental conditions, such as gradients of salinity and temperatures, affect how these worms adapt to their surroundings. This brought Vu and her team to the field and to TREC, where they headed out to coastal sites where the little planarians live among fields of seagrass and algae. <\/p>\n\n\n\n

\"Photograph
Hanh Vu and her teammates at one of the sampling sites. Credit: Hanh Vu\/EMBL<\/figcaption><\/figure>\n\n\n\n

\u201cSince marine planarians tend to stick to submerged rocks, it was important for us to catch them at the right time, when the low tide exposed these rocks,\u201d said Vu. Once they spotted the critters, they used paint brushes to sweep them off the rocks and into the waiting collection tubes. In addition to marine planarians, the team also sampled from freshwater environments. <\/p>\n\n\n\n

\u201cThere are very few previous reports of marine planarians in Iceland,\u201d said Vu. \u201cUnexpectedly, we found that they were actually quite abundant at the sites where we sampled. So that was a pleasant surprise.\u201d<\/p>\n\n\n\n

Soil, sediments, and pollution<\/strong><\/h2>\n\n\n\n

This visit to Iceland was the third pilot expedition in the run-up to TREC, previous editions having taken place in Villefranche, France, and Naples, Italy. Kiley Seitz, a microbial ecologist working at EMBL Heidelberg, has been part of every pilot so far. An expert in soil microbiology, she has coordinated the sampling site selection as well as the sample collection protocols.  Along with other EMBL scientists, she collected soil, water, and sediment samples along \u2018land-sea transects\u2019 \u2013 straight line paths leading from the sea to adjoining lands. <\/p>\n\n\n\n

For this team, the sampling process began with the now-familiar procedure of loading up a car with hundreds of pre-labelled bags and tubes and travelling to predetermined sites. Once there, the teams identified representative land-sea transects and selected sampling spots at regular distances along them, moving away from the sea. <\/p>\n\n\n\n

To collect soil samples, the researchers used a \u2018corer\u2019 \u2013 a long metal tube that can be inserted into the ground at a specified depth and used to dig out a cylindrical section of soil. At each sampling spot, the researchers collected five such samples which they mixed together to form a representative picture of that position.<\/p>\n\n\n\n

\"A
Sara Verstraeten collecting a soil core while Kiley Seitz sorts through previous samples. Credit: Richard Jacoby\/EMBL<\/figcaption><\/figure>\n\n\n\n

Helping collect soil and sediment samples was Richard Jacoby, who is interested in microbial species that can degrade environmental pollutants. He plans to extract pollutants (usually pesticides, pharmaceuticals, or antibiotics) from the samples back at EMBL, and analyse them chemically. <\/p>\n\n\n\n

\u201cIf we start doing this in multiple places, in Iceland or throughout Europe, we can start to get a chemical profile of what pollutants are in each place,\u201d said Jacoby. \u201cAnd then perhaps we can start connecting these chemical datasets to other datasets, particularly those obtained by microbial genome sequencing.\u201d<\/p>\n\n\n\n

In Reykjavik, this team studied two sites -- one of which had acted as a dumping ground for many years but had later been treated with bioremediation protocols. The other was a \u2018pristine\u2019 site, but close to a few aluminium factories. The team collected soil and sediment samples from both with plans to conduct metagenomic and biochemical studies.<\/p>\n\n\n\n

In this, they were joined by Joanna Zukowska, who was also part of the plankton-collecting teams in the early days of the expedition. \u201cI have always dreamed of working in the field,\u201d said Zukowska. \u201cThis was a great opportunity for me to learn more about fieldwork and about marine biology.\u201d<\/p>\n\n\n\n

\"A
Joanna Zukowska collecting sediments from coastal waters. Credit: Richard Jacoby\/EMBL<\/figcaption><\/figure>\n\n\n\n

#WeFreezeontheBeach<\/strong><\/h2>\n\n\n\n

In 2017, EMBL alumnus Jacques Dubochet received the Nobel Prize<\/a> for developing a way to prepare and image biological samples using cryo-electron microscopy, a technique that has made it possible for researchers to study the structure of biomolecules at an unprecedented level of detail. <\/p>\n\n\n\n

\"A
A high-pressure freezer that the team took to Iceland. Credit: Yannick Schwab\/EMBL<\/figcaption><\/figure>\n\n\n\n

Now, researchers are bringing this technique from the lab into the field, greatly expanding the scope of the type of biological samples it can study. In addition to plankton and flatworm-collecting biologists, the Iceland pilot expedition team included electron microscopy specialists who tested out protocols for quickly freezing samples in field conditions (and posted their adventures on Twitter with the hashtag \u201c#WeFreezeOnTheBeach\u201d). <\/p>\n\n\n\n

\u201cIt was very important for us at this stage to consolidate the protocols \u2013 how are we going to collect the samples, store them, reference them etc.,\u201d said Yannick Schwab<\/a>, Head of the Electron Microscopy Core Facility at EMBL Heidelberg. <\/p>\n\n\n\n

One of the teams most interested in this process was that of Ben Engel<\/a> from the University of Basel, Switzerland. The Engel group studies the cellular architecture of marine algae. <\/p>\n\n\n\n

\u201cWe are trying to understand how the chloroplast harvests the energy of light to make the biochemical energy that sustains all life on Earth, and how that energy is then used for carbon fixation,\u201d said Engel. To do this, they carry out cryo-electron tomography, a technique where thin sections of frozen cells can be imaged in 3D at high resolution to reveal their inner structures. During the Iceland expedition, the team tried out some of its sample preparation steps in the field. <\/p>\n\n\n\n

\u201cThis is new. There are very few people doing cryo-electron microscopy in the field,\u201d said Anna Steyer, cryo-ET specialist at EMBL Heidelberg. \u201cWhen you think of fieldwork equipment, you think of binoculars, not of sample preparation for high-end cryo-EM. The power of this technology is opening up new questions that biologists anywhere can now address.\u201d<\/p>\n\n\n\n

The teams tested different types of freezing protocols for different applications, for example, plunge freezing for cryo-electron tomography, or high-pressure freezing for volume-electron microscopy. While for this particular expedition, required equipment was shipped beforehand to Iceland from participating institutions, eventually a truck that travels coast to coast will house the equipment needed for future fieldwork. And that\u2019s EMBL\u2019s mobile lab services. <\/a><\/p>\n\n\n\n

\"Three
Annemarie Perez Boerema and Manon Demulder plunge-freezing small algae cells on a Vitrobot, which the team brought to Iceland. Image credit: Ben Engel\/University of Basel<\/figcaption><\/figure>\n\n\n\n

\u201cThis was an excellent dry-run for what we will be facing next year during TREC,\u201d said Niko Leisch, Operational Manager-EMBL mobile services. \u201cFor me, it was important to see the different groups with different scientific aims in action. Observing their workflows yields important clues that would help us improve on planning for future trips.\u201d<\/p>\n\n\n\n

Traversing Coastal Ecosystems<\/h2>\n\n\n\n

This expedition was many years in the making. EMBL\u2019s new five-year programme \u2018Molecules to Ecosystems\u2019<\/a>, which was launched in January 2022<\/a>, laid down the ambitious goal of advancing our understanding of ecosystems at the molecular level to study life in its natural context. To help achieve this, EMBL initiated several transversal themes<\/a> which support the multidisciplinary science necessary to realise projects like these. One of these themes is Planetary Biology<\/a>, which aims to study, from the molecular to the population level, how microbes, plants, and animals respond to each other and to their environment.<\/p>\n\n\n\n

TREC, a flagship project part of the Planetary Biology theme, aims to study <\/em>coastal ecosystems across Europe and their responses to a fast-changing environment to address environmental challenges to planetary and human health. In realising this goal, EMBL\u2019s researchers and mobile services will work closely together with the Tara Ocean Foundation, the Tara Oceans Consortium (now TaraOceanS), the European Marine Biological Resource Centre (EMBRC), as well as many other national research institutions. <\/p>\n\n\n\n

\u201cGiven the scale and urgency of human and planetary health challenges, it is important for EMBL to organise this large pan-European, highly collaborative and cross-disciplinary project,\u201d said Paola Bertucci, Scientific Expedition Manager for TREC. \u201cEMBL is well positioned to lead this because of its intergovernmental status and large network of collaborators and partners.\u201d<\/p>\n\n\n\n

Throughout this pilot expedition, co-organised by the Icelandic biodiversity research network BIODICE, EMBL researchers and their collaborators interacted closely with their host institutes in Iceland, with whom they formed strong scientific connections and set up future collaborations. It was an opportunity to exchange scientific knowledge as well as expertise, as molecular biologists met marine scientists and ecologists. <\/p>\n\n\n\n

\"A
Johan Decelle from CNRS Grenoble observing a sample under a microscope. Credit: \u00a9Kristinn Ingvarsson\/University of Iceland<\/figcaption><\/figure>\n\n\n\n

\u201cWe had a very positive reaction and a lot of interest from the Icelandic scientific community, and new collaborations were formed around our technologies and scientific questions,\u201d said Leisch. \u201cThis aspect of giving back to the scientists in our member states is a very important one for me, and is one of the central missions of the mobile services.\u201d <\/p>\n\n\n\n

In addition to the scientific activities, the trip also included public engagement and outreach events. On a walk called \u201cScience on the Beach\u201d, coordinated by Sara Verstraeten, TREC Outreach & Public Engagement Manager, members of the public could engage with the expedition scientists to learn more about their work. <\/p>\n\n\n\n

\"A
Kiley Seitz giving a demonstration to visitors during \u2018Science on the Beach\u2019. Credit: \u00a9Bj\u00f6rn G\u00edslason \u2013 BGI \/University of Iceland.<\/figcaption><\/figure>\n\n\n\n

With lessons learned from Iceland, the team looks forward now to preparing for the next expeditions that will begin in France in spring 2023 <\/em>and conclude in Greece nearly 18 months later. <\/p>\n\n\n\n

\u201cIceland is always breathtaking. All day long, one is surrounded by a rather hostile, alien landscape shaped by volcanic activity,\u201d said Leisch. \u201cBut the warmth of the Icelandic people more than makes up for that.\u201d<\/p>\n","post_title":"From coast to coast and beyond","post_excerpt":"EMBL researchers conducted a pilot project in Iceland as the final preparatory step before commencing their journey traversing European coastlines.\n","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"from-coast-to-coast-and-beyond","to_ping":"","pinged":"","post_modified":"2023-02-06 15:20:52","post_modified_gmt":"2023-02-06 14:20:52","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=53294","menu_order":0,"post_type":"embletc","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":53296,"post_author":"100","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"\n

\"\"
Lautaro Gandara, a postdoc in EMBL\u2019s Crocker and Alexandrov groups, spends a good deal of time in Room 611, working with fruit flies to methodically discern the impacts of different pesticide ingredients upon them. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

It\u2019s a long day in room 611 with only fruit fly larvae for company \u2013 some no longer even alive. A young postdoc quickly transfers fruit fly larvae from small vials to Petri dishes with a fine-tipped paint brush. He has decided it\u2019s the gentlest process to nudge them onto the Petri dishes where he can capture their behaviour after they\u2019ve been growing in a nutrient-rich and possibly also chemical-infused medium. <\/p>\n\n\n\n

A video camera records the larvae\u2019s behaviour upon entering the Petri dish. Placed in this \u2018new world\u2019, some immediately scatter this way and that. To the untrained eye, it would seem quite random. But to Lautaro Gandara, a postdoc in EMBL\u2019s Crocker and Alexandrov groups funded by the EMBL EIPOD postdoc programme<\/a>, it has proven to be much more. He spends the next 10 days quantifying the recorded observations, measuring the stops and starts, distance gained, and other variables to yield behavioural and developmental data about the larvae.<\/p>\n\n\n\n

Such is the life of a molecular biologist investigating the effect of agricultural chemicals on a quick-developing organism \u2013 one that is potentially representative of the long-term impacts of pesticide use on living ecosystems.<\/p>\n\n\n\n

Gandara is but one of several researchers at EMBL whose work has intertwined in myriad ways to bring molecular biology insights into understanding the impacts of pesticides, their degradation, and ways to accelerate that degradation. <\/p>\n\n\n\n

EMBL\u2019s new programme, \u2018Molecules to Ecosystems<\/a>, applies some of EMBL\u2019s established approaches for studying molecular and cellular biology to better understand the environment. It is multidisciplinary. And it\u2019s so collaborative it\u2019s hard to see the organisational lines that divide EMBL\u2019s groups and units;  scientists converge to work toward multi-pronged, overlapping research goals within a new transversal theme of planetary biology<\/a>. <\/p>\n\n\n\n

This kind of fundamental research can inform approaches to pollution clean-up and potentially guide a new generation of agro-chemicals \u2013 chemicals that would still be potent enough for their intended objectives, but able to quickly degrade and disappear.<\/p>\n\n\n\n

A library that will keep on giving<\/strong><\/h2>\n\n\n\n

If you ask Michael Zimmermann how his research group began its work with pesticides, he talks about building a library \u2013 a library of chemicals contained in pesticides new and old that can still be found in our environment. <\/p>\n\n\n\n

\"\"
This year, Richard Jacoby (left) and Michael Zimmermann (right) worked with the Swiss water research institute, Eawag to coordinate several field campaigns to look at how biopollutants affect river ecosystems downstream.<\/figcaption><\/figure>\n\n\n\n

A group leader in EMBL\u2019s Structural and Computational Biology unit<\/a>, Zimmermann has been known for his work on the human gut microbiome. As he describes this foray into pesticides, he compares this newest challenge to deciphering how gut bacteria interact with foods and drugs and what that means to a wider collection of systems. Scientists can pinpoint genes within gut bacteria that can chemically modify drugs into metabolites. The same is true for chemicals eliminating weeds, crop pests, mould, and fungi. Once again, microbes can help degrade the chemicals.<\/p>\n\n\n\n

\u201cWe\u2019ve known for decades that bacteria absorb and convert xenobiotics \u2013 chemical substances that are foreign to animal life,\u201d Zimmermann said. \u201cI\u2019m pretty convinced we can apply the same molecular approaches we\u2019ve been using on human-associated bacteria to environmental bacteria. And again, we want to know not just which bacteria do this, but also which gene is responsible for the work.\u201d<\/p>\n\n\n\n

He began this quest by looking for a library of chemicals that his group could pair up with microbes reputed to be chemical killers. The library didn\u2019t exist. So, he and his group talked to various chemical manufacturers. As a result, he approached EMBL's Environmental Research Initiative (ERI)<\/a> for funding that comes from private citizens and Friends of EMBL<\/a>. By 2021 -- thanks to this ERI support -- EMBL had its own library of more than 1,000 chemicals found in pesticides plus the means to recruit a fellow to assist with a bigger project. EMBL\u2019s Chemical Biology Core Facility<\/a>, which already had a drug library of several thousand drug compounds, now stores the chemicals in a multi-well format readily usable for screens at large scale.<\/p>\n\n\n\n

The other half of this equation was, in fact, identifying microbes that could degrade or chemically modify pesticides. Richard Jacoby, became the ARISE research fellow<\/a> to work between the Zimmermann group and EMBL\u2019s Chemical Core Facility, scrutinising scientific literature, identifying approximately 100 environmental microbe candidates that he narrowed down to 30 to represent microbes found in nature.\u00a0<\/p>\n\n\n\n

\u201cWith the pollutants in the environment, we know they degrade and at different rates,\u201d Jacoby said. \u201cThe knowledge gap we want to fill comes from asking \u2018what controls that rate of degradation?\u2019 A lot of the time it\u2019s microbial metabolism. Microbes may break down one chemical while others are more recalcitrant. If we can find which microbe strains break down which chemicals, we can better predict how long a chemical will persist in the environment.\u201d<\/p>\n\n\n\n

To this end, an important part of Jacoby\u2019s work involves a mass spectrometer, which is able to identify the individual components of a given substance by their molecular mass or weight.<\/p>\n\n\n\n

\u201cI culture microbes. I inoculate them with pesticides. And then I use a mass spectrometer to detect whether the microbe has degraded that pesticide,\u201d Jacoby said. \u201cIf it has, I look for what new \u2018transformation products\u2019 have been produced and the effect they could have on ecosystems.\u201d <\/p>\n\n\n\n

From this point on, Zimmermann\u2019s team looks more closely at the bacteria most effective at aiding this degradation. They chop up its genome into small pieces of DNA and clone it into the laboratory bacterium E. coli<\/em>, and look for clones which now take on the same metabolic function of degrading pesticides as the original bacteria.  When they do this with 50 thousand clones and screen them with mass spectrometry, they can identify which particular piece of DNA holds the genes that can degrade pesticides. <\/p>\n\n\n\n

\"\"
In August 2022, EMBL scientists visited Iceland for a final pilot expedition before the launch of EMBL\u2019s \u2018Traversing European Coastlines\u2019 (TREC) project in 2023. Richard Jacoby worked with Joanna Zukowska and Kiley Seitz to collect soil samples from an Icelandic coastline \u2013 samples that will also be reviewed with mass spectrometry. Credit: Joanna Zukowska\/EMBL<\/figcaption><\/figure>\n\n\n\n

But this research only represents a part of a fundamental research picture. The Zimmermann group is beginning and planning other projects that go out into the environment to literally \u2018ground truth\u2019 their work, looking for the same microbial signatures and patterns in soil sediments and waterways to verify their lab findings. <\/p>\n\n\n\n

The intersection of fruit flies and pesticides<\/strong><\/h2>\n\n\n\n

It\u2019s been a few years and \u2018several cups of coffee\u2019 since Zimmermann and Justin Crocker, another group leader but in EMBL\u2019s Developmental Biology unit<\/a>, first chatted during a conference break about the usefulness of having a pesticide library. This seemingly modest encounter ignited the spark that has built such a library and given it increasing purpose.<\/p>\n\n\n\n

It is brightly lit in Crocker\u2019s lab on a sunny summer day in Germany, and there is an air of purpose and energy, radiating from Crocker himself. Zimmermann \u2013 as well as everyone interviewed for this story \u2013 convey this same positive vibe. Their myriad approaches complement one another, and despite tedious parts in the process \u2013 babysitting a mass spectrometer or systematically observing day-to-day changes in fruit fly larvae \u2013 it\u2019s clear the involved researchers are excited about what their work will tell them and how it fits into understanding pesticides better.<\/p>\n\n\n\n

The researchers in Crocker\u2019s lab work with a model organism \u2013 fruit flies. <\/p>\n\n\n\n

\"\"
Lautaro Gandara and Justin Crocker stand in the room where fruit flies are cared for during their involvement in research at EMBL Heidelberg. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

EMBL has a history with fruit flies. Christiane N\u00fcsslein-Volhard and Erich Wieschaus were EMBL\u2019s first researchers to be awarded a Nobel Prize in Medicine. In 1995, they were recognised for conducting the first systematic genetic analysis of fruit fly embryonic development, having identified genes responsible for the body plan of the insect embryos.<\/p>\n\n\n\n

\u201cUsing fruit flies, they looked at what you can learn when you break down a system into its barest parts,\u201d Crocker explained. \u201cWe have this beautiful groundwork done here at EMBL. We\u2019re now building on that to look at the whole system \u2013 essentially, putting it back together.\u201d<\/p>\n\n\n\n

With their simple body plan and quick growth, fruit flies can quickly add to the body of knowledge that EMBL\u2019s pesticide library affords. Crocker brought with him high-throughput approaches for doing this kind of work from his own postdoc experience at Howard Hughes Medical Institutes\u2019 Janelia Research Campus in the US. <\/p>\n\n\n\n

When Gandara isn\u2019t gathering data in room 611 or in the \u2018Fly Room\u2019 studying adult fruit flies, he is in Crocker\u2019s lab. He follows each generation of fruit flies from larva to adulthood to track various chemicals\u2019 effects on growth and development.<\/p>\n\n\n\n

The fruit flies he observed on the Petri dishes \u2013 bending, rolling, stopping, starting \u2013 are moved to bigger vials to observe daily until they reach adulthood \u2013 approximately 10 days. Two incubation rooms have been set up \u2013 each with different temperatures to control the speed of the fruit fly life cycle. Vials reside within both, each filled with a cornmeal-based medium cushioning and nourishing the flies until maturity. So far, Gandara has collected data on acute toxicity, impact of chemicals on fruit fly activity levels, and survival rates. <\/p>\n\n\n\n

Additionally, the Crocker group has \u2018germ-free\u2019 fruit flies they use in a \u2018gnotobiotic\u2019 environment \u2013 essentially a completely sterile environment where the only microbes present are the ones the researchers introduce. By isolating microbes and fruitflies in this way, they gain control of microbiome variables and can see the impact they have on the presence of pesticides in the fruit flies\u2019 microbiomes.<\/p>\n\n\n\n

\u201cUltimately, we\u2019ll have three complete datasets for the chemicals,\u201d Gandara said. \u201cThese datasets will inform us about the effects of these chemicals on normal fruit flies, germ-free flies, and bacterial microbes isolated directly from the flies\u2019 guts.\u201d<\/p>\n\n\n\n

\u201cBy looking at how pesticides affect the insect microbiome, we are filling a major knowledge gap,\u201d Jacoby said. \u201cMost work on insect pesticide toxicology has ignored the microbiome. This could provide a wealth of new information about how pesticides affect this host-microbe system.\u201d<\/p>\n\n\n\n

But Gandara\u2019s work doesn\u2019t end there. His position at EMBL crosses unit lines, and his next role in this research involves mass spectrometry and metabolomics, through EMBL\u2019s Alexandrov group.<\/p>\n\n\n\n

Nature vs. nurture and the role of metabolomics<\/strong><\/h2>\n\n\n\n

Metabolomics studies small molecules commonly known as metabolites, products of metabolism that fill and fuel all cells, biofluids, tissues, and organs. Because metabolites are influenced by both genetic and environmental factors, they are able to indicate individual cells\u2019 underlying biochemical activity and their current state or status. Researchers use mass spectrometry to suss out this information.<\/p>\n\n\n\n

\n
\"\"<\/figure>\n\n\n\n
\"\"<\/figure>\n
Lautaro Gandara and Mans Olof Ekelof conduct metabolomics studies to produce a deeper phenotypic analysis for understanding pesticide impacts. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

In the case of fruit flies\u2019 response to myriad chemicals, Theodore Alexandrov, an EMBL team leader in EMBL\u2019s Structural and Computational Biology unit, had already been working with the Crocker Group prior to the pesticide library.<\/p>\n\n\n\n

\u201cWe considered what would be a good way to profile molecular changes caused by environmental stimuli,\u201d Alexandrov said. \u201cPesticides are just one such stimuli. It could just as easily have been temperature or any other environmental factor.\u201d<\/p>\n\n\n\n

Gandara works with Mans Olof Ekelof, an Imaging Mass Spectrometrist in the Alexandrov group, to produce a deeper phenotypic analysis that metabolomics affords. By placing larvae onto glass slides, scanning them with a laser that desorbs or releases amino acids, carbohydrates, and lipids, they can identify and measure spatial distributions of metabolites within the larvae. In this way, Ekelof\u2019s mass spectrometry data is able to confirm Gandara\u2019s biological observations.<\/p>\n\n\n\n

In the coming months, Gandara and Ekelof will leverage this cutting-edge technology to study metabolic changes triggered by different agrochemicals. By doing so, they hope to provide a comprehensive view \u2013 encompassing development, behaviour, and metabolism \u2013 of how organisms deal with stressful environmental conditions. <\/p>\n\n\n\n

The future<\/strong><\/h2>\n\n\n\n
\"\"
Quince fruit in EMBL Heidelberg. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

Right now, these research groups are still compiling data. That doesn\u2019t stop them from thinking about follow-on projects. The Crocker group looks to a time when they can collect fruit flies from around the world to further understand the natural biomes they inhabit. <\/p>\n\n\n\n

The Zimmermann group has just recently become involved with Eawag, a leading water research institute in Zurich. With funding from the Swiss National Science Foundation and the German Research Foundation, they coordinated several field campaigns this year to look at how biopollutants affect the river ecosystem downstream. Targeting six wastewater treatment facilities in Switzerland, they are just beginning to look at the microbiomes upstream and downstream from these facilities to observe microbes in action in the real world. <\/p>\n\n\n\n

Additionally, other EMBL researchers are engaged in pesticide research projects unrelated to the library at this point. <\/p>\n\n\n\n

Recently, <\/a>ERI announced that their latest grant would support the Pepperkok team as it explores how microbial mats in the ocean break down chemical pollutants using spatial-omics. Once again, <\/a>Friends of EMBL and other citizens provided this new funding.<\/p>\n\n\n\n

Members of the Bork group are also hoping to establish interaction maps between chemical compounds and microbes, individually and in communities using advanced multi-omics approaches, with application for human (e.g., individualised diet) or planetary health (e.g., pesticide response biomarkers).<\/p>\n\n\n\n

And this latest work by Jacoby follows on a previous project he pursued \u2013 also thanks to ERI funding \u2013 that measured toxic pollutants in specific plankton species to better understand their mechanisms of bioaccumulation with the intent that his findings might also inform the design of green chemicals.<\/p>\n\n\n\n

\u201cI\u2019m quite positive about being at EMBL during this new five-year programme where I\u2019m encouraged to think about and pursue molecular approaches to planetary biology issues,\u201d Jacoby said. \u201cOur modern life has come to depend on the chemical industry for necessary pharmaceutical drugs and agricultural production. If we discontinued their use, what would happen to global health? To agricultural production? Hopefully, we can help others have information they need to build degradable replacements to these chemicals.\u201d<\/p>\n","post_title":"The power of a pesticide library","post_excerpt":"EMBL research groups apply molecular biology and its research tools to better understand agricultural pesticides\n","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"the-power-of-a-pesticide-library","to_ping":"","pinged":"","post_modified":"2023-03-31 14:36:15","post_modified_gmt":"2023-03-31 12:36:15","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=53296","menu_order":0,"post_type":"embletc","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":53298,"post_author":"96","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"\n

Sunlight delivers precious energy that organisms capture using specialised molecular \u2018solar panels\u2019. Only two kinds of molecules can achieve this: chlorophyll-based proteins, which enable photosynthesis, and rhodopsins. Besides capturing solar energy, rhodopsins are also present in the retina and enable us to see.<\/p>\n\n\n\n

In contrast to green chlorophyll-based proteins, which dominate on land, rhodopsins are mostly purple and found in aquatic microorganisms, especially ocean-living bacteria, archaea, algae, and even some giant viruses. <\/p>\n\n\n\n

Kirill Kovalev, an EIPOD<\/a> postdoc in the Schneider Group<\/a> at EMBL Hamburg and the Bateman Group<\/a> at EMBL-EBI, is fascinated by microbial rhodopsins. Trained as a physicist, he uses cutting-edge structural biology techniques to create molecular stop-motion visualisations showing how rhodopsins change their molecular structure to capture solar energy. With this knowledge, he designs new, more powerful rhodopsins that neuroscientists could apply as tools to control neuronal activity.<\/p>\n\n\n\n

The many colours of molecular solar panels<\/strong><\/h2>\n\n\n\n
\"Shoreline
The purple-pink colour of rhodopsins can be seen in some salty lakes with high numbers of rhodopsin-carrying microorganisms. An example is Lake Hillier in Australia, also known as the Pink Lake.
Credit: Adobe Stock.<\/figcaption><\/figure>\n\n\n\n

Why are rhodopsins and chlorophylls so colourful? The colour that we see is the light that these molecules reflect while absorbing all other wavelengths. For example, rhodopsins capture green and blue light and reflect purple wavelengths. Different types of rhodopsins reflect slightly different ranges of wavelengths, which gives them different hues of purple, violet, pink, and orange. Which wavelengths are absorbed or reflected is determined by the molecule\u2019s structure. Rhodopsins have a simpler structure than chlorophylls and are believed to be evolutionarily older.<\/p>\n\n\n\n

Switching cells on and off with light<\/strong><\/h2>\n\n\n\n

Rhodopsins\u2019 ability to absorb specific light wavelengths not only gives them their pretty colours but also makes them scientifically interesting. In particular, one group of rhodopsins found in algae, called channelrhodopsins, is studied for its unique ability to trigger electrical activity in cells when exposed to blue light. <\/p>\n\n\n\n

Scientists have adapted channelrhodopsins for human and animal cells, such that they can be used like an on- and off-switch for cellular activity. This technique, called \u2018optogenetics\u2019, was a game-changer for neuroscientists because it enables them to precisely and quickly stimulate selected neurons in the brain with just a flash of light. <\/p>\n\n\n\n

Expanding the rhodopsin colour palette<\/strong><\/h2>\n\n\n\n
\"Over
Kirill Kovalev is holding two syringes containing rhodopsin crystals. Credit: Kinga Lubowiecka\/EMBL. <\/figcaption><\/figure>\n\n\n\n

Currently, scientists have only a few channelrhodopsins to pick from, which makes certain experiments difficult or even impossible. To address this, Kovalev is on the search for new, more powerful rhodopsins that could also be activated with other colours of light.<\/p>\n\n\n\n

Using X-rays, he compares different rhodopsins found in bacteria, often in exotic places, such as salty lakes or glaciers. This lets him understand how tiny differences in the molecular structure determine protein properties and function, for instance, which colours a particular rhodopsin is sensitive to. <\/p>\n\n\n\n

\u201cOften, we are comparing almost identical rhodopsin variants,\u201d said Kovalev. \u201cA difference of just one atom is enough to change the molecule\u2019s properties. That\u2019s why we need to analyse them at atomic resolution.\u201d<\/p>\n\n\n\n

One advantage of these comparisons is that they let Kovalev predict which modifications would make rhodopsins responsive to new colours. Then, he and his collaborators can create these rhodopsins in the laboratory and test them. <\/p>\n\n\n\n

Rhodopsins in stop-motion<\/strong><\/h2>\n\n\n\n
\"Closeup
Two syringes containing crystals of sodium (pink) and proton (purple) transporting rhodopsins. Grown in syringes, the crystals will be loaded into a special injector, which is then mounted at the P14 beamline for time-resolved X-ray studies. Credit: Kinga Lubowiecka\/EMBL. <\/figcaption><\/figure>\n\n\n\n

What happens when a rhodopsin absorbs light? First, it gives rise to a complicated series of changes in the structure of the rhodopsin molecule. To visualise this process in detail, Kovalev uses a technique called time-resolved X-ray crystallography at EMBL Hamburg\u2019s beamline P14. This experimental facility is adapted for particularly demanding crystallography experiments. X-ray crystallography enables Kovalev to take snapshots of a rhodopsin at specific timepoints after absorbing light and combine them into a stop-motion movie. <\/p>\n\n\n\n

\u201cStudying a molecule that undergoes so many changes within just milliseconds is extremely challenging. Besides, rhodopsins are membrane proteins. Such proteins are notoriously difficult to crystallise, which makes them even trickier to work with,\u201d said Kovalev. \u201cBut I can do this at EMBL Hamburg\u2019s beamline P14 at PETRA III, which is one of the best in the world for this type of experiments.\u201d <\/p>\n\n\n\n

Kovalev was one of the first at EMBL Hamburg to attempt a time-resolved crystallography experiment on a membrane protein. Before he could start experiments, the Schneider Group worked together, each member contributing different expertise, to make the beamline setup suitable for Kovalev\u2019s project. Besides adjustments for membrane proteins, they installed a system to emit a flash of light to activate the rhodopsins, coordinated with the X-ray beam that would take a snapshot precisely at a selected timepoint milliseconds later. <\/p>\n\n\n\n

\"Photo
The setup for time-resolved X-ray crystallography at the EMBL Hamburg beamline P14 allows taking snapshots of molecules precisely at selected timepoints. It enables scientists to create molecular stop-motion movies of molecules that change their structure over time. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

In addition to the EMBL beamline P14, Kirill also performs experiments at the European XFEL<\/a>, which allows for time resolution in the range of femtoseconds (one quadrillionth of a second). <\/p>\n\n\n\n

\u201cThis combination of having a synchrotron and XFEL in one place is very helpful. Besides Hamburg, only Japan and Switzerland have a combo like this,\u201d said Kovalev.<\/p>\n\n\n\n

In the coming years, time-resolved experiments at EMBL Hamburg, such as this, will be further improved upon to observe how proteins work with even better time resolution. This will be possible with the planned upgrade of the synchrotron PETRA III to PETRA IV<\/a>. <\/p>\n\n\n\n

Using light to hear better<\/strong><\/h2>\n\n\n\n
\"Photo
Tubes containing bacterial rhodopsin found in a glacier. In each tube, the colour is different because of different pH values. Credit: Kirill Kovalev\/EMBL.<\/figcaption><\/figure>\n\n\n\n

Kovalev, a physicist by training, first started to work on rhodopsins during his bachelor\u2019s studies. <\/p>\n\n\n\n

\u201cWhat got me interested in biology was the opportunity to apply physics methods to solve unsolved problems. I like the thrill of being the first one to see how the molecule moves and understand how it works. I also like that my work can potentially help others in research and medicine,\u201d he said.<\/p>\n\n\n\n

One of the collaborative projects he\u2019s involved in focuses on developing optogenetic tools to treat hearing loss. Kovalev, together with the Institute of Auditory Neuroscience<\/a> at G\u00f6ttingen University, aims to develop new rhodopsins that would help improve hearing quality in patients with cochlear implants.<\/p>\n\n\n\n

In the new approach, rhodopsins will be placed into the cochlear auditory nerve using gene therapy. The nerve transmits information from the ear towards the brain, where it\u2019s interpreted as sound. Neurons at different parts of the nerve respond to different sound properties, such as pitch or intensity. A new generation of cochlear implants produces patterns of light stimuli that activate these different parts. By encoding sound information with light, these newer implants could stimulate the cochlear nerve with increased precision, allowing patients to better hear fine differences between sounds.<\/p>\n\n\n\n

This wouldn\u2019t be possible without new powerful and fast-acting rhodopsins that could manage the complexity of quickly changing sounds around patients.<\/p>\n\n\n\n

This project is just one example of how clinics could use designer rhodopsins. New rhodopsins might offer new applications in other areas as well. <\/p>\n\n\n\n

\u201cI believe the unique structural data we decipher will serve not only to help us understand fundamental principles of light energy use and reveal new cellular processes on Earth,\u201d Kovalev said. \u201cIt will also contribute to developing rhodopsin-based biotechnology and medicine.\u201d<\/p>\n","post_title":"Molecular solar panels can help scientists control brain cells","post_excerpt":"Kirill Kovalev, an EMBL Hamburg researcher, is studying the structure of an ancient bacterial molecule to help scientists control brain cell activity","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"molecular-solar-panels-can-help-scientists-control-brain-cells","to_ping":"","pinged":"","post_modified":"2025-03-24 11:18:29","post_modified_gmt":"2025-03-24 10:18:29","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=53298","menu_order":0,"post_type":"embletc","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":53300,"post_author":"47","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"\n

Having one bioinformatician on a research team used to be enough, but as biology becomes more data-driven, bioinformaticians are in high demand. <\/p>\n\n\n\n

This is certainly the case in Latin America, where the data revolution is well underway in the life sciences. But one thing that is still missing is a critical mass of bioinformaticians to manage, analyse, and share the data more widely. <\/p>\n\n\n\n

\"Aerial
Aerial shot taken during a CABANA visit to Bel\u00e9m in Brazil. Credit: Jeff Dowling\/EMBL-EBI<\/figcaption><\/figure>\n\n\n\n

Bioinformatics - getting insights from big data<\/strong><\/h2>\n\n\n\n

Bioinformatics is the science of analysing, managing, storing and sharing biological data, usually on a large scale. Discovery and innovation rely on scientists sharing the data generated by their experiments; this way, the data can be reused by others to explore different scientific questions and gain new insights. <\/p>\n\n\n\n

But as the number and scale of experiments increase \u2013 and more data are generated \u2013 the need for specialist databases, analysis tools, and data experts becomes urgent.<\/p>\n\n\n\n

Bioinformatics enables scientists to exploit the large datasets available in public data resources such as the ones managed by EMBL\u2019s European Bioinformatics Institute (EMBL-EBI), to answer diverse research questions, for example:<\/p>\n\n\n\n