Tosches\u2019 research \u2013 recognised with EMBL\u2019s 2022 John Kendrew Award for original contributions to the field of brain evolution \u2014 is testament to her commitment to a calling very different from her parents, who are farmers still in Italy. But it is also a demonstration of the work ethic and values she has held dear throughout her personal and professional life.<\/p>\n\n\n\n
\u201cMy parents put 100 % into everything they do,\u201d Tosches said. \u201cIt\u2019s from them that I learned to strive for excellence. I see this in myself when I am running my projects, setting priorities \u2013 trying to do the best things possible in the best possible way. It\u2019s been 20 years since I left my village, and I would never have imagined this kind of work for myself then.\u201d<\/p>\n\n\n\n
From worms to turtles to newts<\/strong><\/h2>\n\n\n\nEven before Tosches earned her PhD at EMBL, she was studying the development of retinas in frogs. She joined Detlev Arendt\u2019s group at EMBL Heidelberg where his group was exploring the evolution of neurons, using the Platynereis<\/em> worm\u2019s nervous system as a model organism. <\/p>\n\n\n\nAt EMBL, Tosches took up work that Arendt had started as a postdoc when he discovered photoreceptor cells similar to those found in retinas, but in the middle of a Platynereis <\/em>larva\u2019s brain. She wanted to understand why they were there. Through a series of experiments, she discovered these cells are part of a larger group that produces melatonin, a chemical that essentially helps tell a body when it\u2019s time to sleep. In the case of the worm larvae, swimming and dispersing in the sea, the melatonin is used by these photoreceptor cells to sense when it is night or day so the worm larvae\u2019s swimming circuits can slow down during night. <\/p>\n\n\n\n\u201cThis work showed how the same molecule is used in animals that diverged from human\u2019s evolutionary path 600 million years ago, to do something very similar \u2013 controlling circadian rhythms of locomotion,\u201d Tosches explained. \u201cThe light-dependent control of locomotion is something that has existed since the beginning of the evolution of animal nervous systems. Other researchers discovered that even jellyfish sleep, and melatonin modulates or is involved in sleep mechanisms. This link between sleep and melatonin is something very, very ancient in animals.\u201d<\/p>\n\n\n\n
In 2014, Tosches joined the group of Gilles Laurent at the Max Planck Institute for Brain Research as a postdoc. There, she used a single-cell approach to study the evolution of cerebral cortices in turtles and lizards, choosing them because they have the simplest cerebral cortex. <\/p>\n\n\n\n
\u201cFor many decades, scientists have been comparing the brains of frogs, fish, turtles, and of course, mammals, and describing the neuroanatomy of these brains,\u201d Tosches said. \u201cBut what’s still obscure is how the differences<\/em> between these different vertebrate brains came about.\u201d<\/p>\n\n\n\n![\"Photo](\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/Spanish_Ribbed_Newt_1_retouched-1024x683.jpg\")
In five to 10 years, the EMBL alumna hopes the Spanish ribbed newt, Pleurodeles waltl<\/em> will help her to create a complete, cell-by-cell description of how neural circuits are assembled and organised in a vertebrate brain. Credit: Wenze Li<\/figcaption><\/figure>\n\n\n\nAdditionally, Tosches has been interested in learning more about the cognitive capacities of vertebrates besides what has been gleaned from mice, primates, and humans. <\/p>\n\n\n\n
\u201cAbout 320 million years ago, one vertebrate evolutionary line led to us mammals, and another led to reptiles and birds. And in these passing years, lots of changes happened,\u201d she said. \u201cEventually, mammals and birds acquired very high cognitive abilities independently. Birds are incredibly smart and have been studied more than other vertebrates with simpler cognition, which are not understood at all yet.\u201d<\/p>\n\n\n\n
Since 2019, she has led her own research lab at Columbia University. With newts, Tosches uses genetic, genomic, developmental, and neurobiological approaches to investigate the evolution of brain cell types and neural circuits in the vertebrate brain.<\/p>\n\n\n\n
\u201cWe are trying to understand whether salamanders can use landmarks to understand their location,\u201d she explained. \u201cA part of the brain involved in navigation, the hippocampus, has an innate ability to know where you are in space. We found that cell types there that help make this happen also exist in other species.\u201d<\/p>\n\n\n\n
In early September, her research group and collaborators published a paper in Science<\/em><\/a> exploring the similarities and differences of neuron types in the forebrains of salamanders, turtles, lizards, and mice.<\/p>\n\n\n\nWhy evolutionary neuroscience is important<\/strong><\/h2>\n\n\n\n\u201cI am driven by curiosity,\u201d Tosches said, talking about the future of her research. <\/p>\n\n\n\n
In five to 10 years, the EMBL alumna hopes to have created a complete, cell-by-cell description of how neural circuits are assembled and organised in a vertebrate brain. It\u2019s a \u2018dream that drives\u2019 her to think about her lesser-known Spanish ribbed newt Pleurodeles waltl <\/em>ultimately <\/em>being recognised as a model organism in much the same way that C. elegans<\/em> is extolled for its role in understanding neural circuitry.<\/p>\n\n\n\nAnd in the world of fundamental scientific research, that\u2019s a very big deal.<\/p>\n\n\n\n
\u201cIf we look back at history, all the major breakthroughs in biology \u2013 and in science in general \u2013 came not because someone anticipated or planned for the societal impact or the impact on human health,\u201d she said. \u201cThat\u2019s the beauty of fundamental research. At the time many of these kinds of discoveries are made, nobody \u2013 not even the person who makes the discovery \u2013 is really aware of the influence they may have in future scientists\u2019 work or how the science can change how we think about and do things.\u201d<\/p>\n\n\n\n
Being \u2018fearless about your science\u2019<\/strong><\/h2>\n\n\n\nTosches\u2019 determination to reach this goal is quite evident. Her voice only grows stronger as she shares more details from her current work. However, she is quick to add \u2013 more than once \u2013 that this drive not only comes from her parents but a culture of risk taking at EMBL.<\/p>\n\n\n\n
\u201cWhat did I learn during my time at EMBL? Not to be afraid of trying new things,\u201d she said. \u201cYou are surrounded by people doing amazing science in so many different fields; it’s not like other institutes. The environment encourages you to talk to others even about things you yourself barely understand\u2026 you learn from each other.\u201d<\/p>\n\n\n\n
She speaks of this experience as uniquely motivating, teaching her to \u2018dream big\u2019 and \u2018try new things\u2019. And her example of living this mantra comes in her own postdoc experience following EMBL. Upon learning of new sequencing technology available that could process thousands of cells at a time, she changed research direction, abandoning her original postdoc project to focus on a transcriptomics single-cell approach, finding herself ultimately \u2018more satisfied\u2019 in the new undertaking.<\/p>\n\n\n\n
\u201cEMBL is very special, and consequently it has aspects impossible to replicate in a single research lab,\u201d Tosches said. \u201cHowever, what I am passing down to my students and postdocs is the idea of being fearless about the science they’re doing. We try new things every day because we’re working on a new system, a new animal, a new model. It\u2019s important to be positive \u2013 with the attitude of open-minded explorers who seize on new, unplanned opportunities and even find unexpected results.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"
Newts act as model organisms for Maria Tosches, winner of the 2022 John Kendrew Award, to further explore the cellular makeup of vertebrate brains.<\/p>\n","protected":false},"author":100,"featured_media":53974,"parent":0,"menu_order":0,"template":"","tags":[],"class_list":["post-53302","embletc","type-embletc","status-publish","has-post-thumbnail","hentry"],"acf":{"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"
Newts act as model organisms for Maria Tosches, winner of the 2022 John Kendrew Award, to further explore the cellular makeup of vertebrate brains.<\/span><\/p>\n","related_links":[{"link_description":"2022 EMBL Alumni Awards Winners announced\r\n","link_url":"https:\/\/www.embl.org\/news\/alumni\/2022-embl-alumni-award-winners-announced\/"},{"link_description":"EMBL Alumni Relations programme\r\n","link_url":"https:\/\/www.embl.org\/about\/info\/alumni\/"}],"source_article":false,"in_this_article":false,"press_contact":"None","article_translations":false,"languages":"","embletc_issue":[{"ID":53290,"post_author":"124","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"","post_title":"Issue 99","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"issue-99","to_ping":"","pinged":"","post_modified":"2022-11-17 11:34:48","post_modified_gmt":"2022-11-17 10:34:48","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc-issue&p=53290","menu_order":0,"post_type":"embletc-issue","post_mime_type":"","comment_count":"0","filter":"raw"}],"embletc_in_this_issue":[{"ID":53304,"post_author":"16","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"\nBy Tom Furnival-Adams<\/em><\/p>\n\n\n\nAs she reflects on her long, successful career, it is clear that Sara A. Courtneidge has always been driven, primarily, by an innate compulsion to discover how things work. <\/p>\n\n\n\n
Growing up in Sussex, England, she recalls excitedly rushing to the butcher\u2019s shop on her way home one day to obtain a cow eye to dissect, having been shown the ropes by a particularly enthusiastic science teacher. She also remembers taking it upon herself to examine her family\u2019s tap water using a microscope borrowed from one of her brothers\u2019 chemistry kit. <\/p>\n\n\n\n
And while these formative experiments ensured her family always boiled their water and thoroughly washed chopping boards, they also indicated early on Courtneidge\u2019s burning curiosity about the natural world that would shape the rest of her life.<\/p>\n\n\n\n
It is this extraordinary will to examine and better understand crucial mechanisms of biology that led to her 2022 Lennart Philipson Award<\/a> recognising her major contributions to foundational and translational cancer research.<\/p>\n\n\n\nThis could be perceived as her career coming almost full circle: Philipson was the Director General who recruited Courtneidge to EMBL in 1985. \u201cI had some fantastic interactions with Lennart; he was a wonderfully supportive man. I owe a lot to him,\u201d she said.<\/p>\n\n\n\n
The chemistry of serendipity<\/strong><\/h2>\n\n\n\nCourtneidge, who attended one of Britain\u2018s first comprehensive schools, attributes much of her early success to serendipity. She considers it a stroke of luck that she was taught by a PhD-level chemistry teacher, and was one of a handful of students in her year encouraged and supported to attend university. \u201cMy life has just been these series of fortuitous things,\u201d she said.<\/p>\n\n\n\n
In 1972, she went to the University of Leeds, having \u201cannounced\u201d that she intended to do so to parents who were both slightly bemused by, and extremely supportive of, their daughter\u2019s boldness. She was only the second member of her family to attend university and believes that her undergraduate degree in biochemistry set her up for the rest of her career. \u201cIt was a really good basis for everything we understand about modern molecular biology now,\u201d she said.<\/p>\n\n\n\n
Her PhD took her to the now-defunct National Institute for Medical Research in Mill Hill, London, where she specialised in virology and immunology. There she first encountered the role of T cells in recognising virus infection. <\/p>\n\n\n\n
\u201cI was working within two labs, one led by an immunologist, and the other led by a virologist, using influenza virus genetics to study how the T cells interact with viruses. It's been interesting helping my friends and colleagues understand pandemics because we had a lot of conversations in my lab about pandemics and how you track them,\u201d Courtneidge recalled.<\/p>\n\n\n\n
Courtneidge would have likely have continued down that path if not for one of her PhD advisors, the virologist Sir John Skehel, intervening. \u201cJohn said, you shouldn't do the same thing for your postdoc that you did for your PhD,\u201d she recounted. \u201cThis is a time to broaden your horizons.\u201d<\/p>\n\n\n\n
Courtneidge began spending more time in the library, consciously following new, different trails of curiosity. She and Skehel discussed various scientific ideas at the lab bench all day long. That\u2019s how she settled upon cancer virus research.<\/p>\n\n\n\n
With Skehel\u2019s endorsement, Courtneidge became interested in the recently discovered novel retroviruses, and he helped her decide to pursue this in one of the labs on the US West Coast. Having never flown before and having only been abroad once, she found herself on a plane bound for University of California, San Francisco to work with the respected microbiologist J. Michael Bishop.<\/p>\n\n\n\n
Bishop was later awarded the 1989 Nobel Prize in Physiology or Medicine with Harold Varmus, with whom he discovered the first human oncogene, c-src<\/em> , which they were using to study cancer. Meanwhile, colleagues in the lab had just determined the protein that this particular oncogene made, c-Src. It had also just been discovered in another lab that the Src protein was a kinase \u2013 an enzyme that adds phosphate groups onto other proteins.<\/p>\n\n\n\nCourtneidge found she was one of the few scientists in the lab familiar with biochemistry and how to handle proteins. \u201cPeople were saying, \u2018Gosh, I wish there was a way we could find out where this protein is in the cell and what it does.\u2019 And I said \u2018this is something I know how to do\u2019,\u201d she said.<\/p>\n\n\n\n
\u201cIt was an amazing time to work on oncogenes,\u201d Courtneidge said. \u201cNow we had this single protein that could turn a normal cell into a cancer cell. There was this push to work out how it does that. That\u2019s when I started working on Src in the lab.\u201d<\/p>\n\n\n\n![\"\"](\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/PastedGraphic-1_retouched.jpg\")
Sara Courtneidge in 1985. Credit: Sara A. Courtneidge<\/figcaption><\/figure>\n\n\n\nAfter her PhD, Courtneidge returned to the National Institute for Medical Research. It had recently been discovered by scientists at the Salk Institute that a DNA tumour virus oncogene called middle T had some kinase activity associated with it \u2013 but they couldn't show that it was a kinase itself. Once again, she possessed the skills and knowledge in the right place at the right time: \u201cI had all the tools from working on Src and Alan Smith\u2019s lab at NIMR had all the tools for working on polyomavirus and the middle T oncogene.\u201d<\/p>\n\n\n\n
Courtneidge collaborated with Smith and discovered that the Src protein binds to middle T protein produced by DNA tumour viruses when they infect the cell. That switches on Src activity that causes cancer. This major finding united two different research fields and paved the way for further developments.<\/p>\n\n\n\n
\u201cGenerally, most DNA viruses just take the brake away [from cell cycle regulation). But the polyomavirus both takes the brakes away and expresses a very potent tumour virus oncogene which activates the accelerator. It was pretty clear at the outset that that was a fundamental reuniting of the tumour virus fields, which were split for a while, and it started a lot of other research,\u201d said Courtneidge.<\/p>\n\n\n\n
Becoming EMBL\u2019s first female senior scientist<\/strong><\/h2>\n\n\n\nIn 1985, Courtneidge brought this research to EMBL, where she was, for a long period, the only female group leader. She later became EMBL\u2019s first female senior scientist. <\/p>\n\n\n\n
\u201cIt's an intolerable burden on women to be the one example of a woman in a room because then, if you give a bad talk, it is generalised into \u2018women give bad talks\u2019,\u201d she said. \u201cIf your paper isn't well received, it\u2019s \u2018women's papers are inferior\u2019.\u201d Courtneidge has been a passionate and active spokesperson for gender equality in science throughout her career, believing better representation is key. <\/p>\n\n\n\n
Courtneidge credits EMBL\u2019s multicultural environment for her insights into the many ways to approach research questions. She also recalls a \u201ccollaborative spirit and an open mindedness\u201d that fostered trust between colleagues and prioritised idea sharing above competition.<\/p>\n\n\n\n
\u201cI have never had more than 10 people in my lab since EMBL,\u201d she said of the impacts EMBL has had on her approach. \u201cHaving a smaller lab helps collaboration; it's not just about how many papers you produce and doing your own thing.\u201d<\/p>\n\n\n\n![\"\"](\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/PastedGraphic-2_retouched1-1024x736.jpg\")
Courtneidge group members in the late 1980s. Top row, left to right: Stefano Fumagalli, Leonardo Brizuela, Manfred Koegl, Thorsten Erpen, Geraldine Twamleyl-Stein. Bottom row, left to right: Gema Alonso, Angelika Heber, Serge Roche, Margaret Jones. Credit: Sara A. Courtneidge<\/figcaption><\/figure>\n\n\n\nTranslational research and industry beckon<\/strong><\/h2>\n\n\n\nAfter nearly 10 years in Heidelberg, industry called. <\/p>\n\n\n\n
\u201cAt EMBL, we were publishing great papers, left, right and centre with wonderful people in my lab,\u201d she said. \u201cBut I reached a point where I asked, \u2018Is there more\u2019?\u201d<\/p>\n\n\n\n
An opportunity in San Francisco caught her attention.<\/p>\n\n\n\n
\u201cIf you want to develop treatments for people based on all the amazing scientific discoveries that were happening in the oncogene field, you had to apply that in some way. And I just thought: \u2018I need to put my money where my mouth is,\u2019\u201d she said.<\/p>\n\n\n\n
Courtneidge joined SUGEN Inc. as Head of Research in 1994, where she guided novel kinase discovery and validation efforts in oncology, and developed the company\u2019s research operations. Her own research had to move to the backburner while she focused on the company\u2019s priorities, but Courtneidge has no regrets. She believes scientists should gain experience in both translational and fundamental research. <\/p>\n\n\n\n
\u201cHow are you going to sell your research to a company if you haven\u2019t thought through what they\u2019d be interested in? What are the potential risks? What are the economics?\u201d she said.<\/p>\n\n\n\n
Realising the day-to-day demands of business administration were leaving her little time for the scientific research she loved, Courtneidge ultimately returned to academia in 2001 to establish a lab at the Van Andel Research Institute in Grand Rapids, Michigan, focusing on applying fundamental research on how cancer cells move to identifying ways to interfere with metastasis.<\/p>\n\n\n\n
She has since served as a professor and Director of the Tumor Microenvironment and Metastasis Program, and Director of Academic Affairs, at the Sanford Burnham Medical Research Institute, before joining Oregon Health and Science University in 2014, where she worked as an Associate Director of Translational Sciences for the Knight Cancer Institute.<\/p>\n\n\n\n
Courtneidge\u2019s work over a number of decades has significantly contributed to understanding oncogene transformation, regulation, substrate selection, and function.<\/p>\n\n\n\n
But Courtneidge is characteristically humble about her legacy. Instead of awards or accolades, she focuses on discoveries and new knowledge. <\/p>\n\n\n\n
\u201cI want to leave a body of work and a toolbox for others to carry it forward,\u201d she reflected. \u201cI stood on the shoulders of giants, and I want everybody to keep climbing upwards towards better understanding\u201d.<\/p>\n","post_title":"From academia to industry and back","post_excerpt":"Sara A. Courtneidge, recipient of the 2022 Lennart Philipson Award, reflects on the fundamental and translational research aspects of her career in cancer research","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"from-academia-to-industry-and-back","to_ping":"","pinged":"","post_modified":"2022-11-16 12:38:21","post_modified_gmt":"2022-11-16 11:38:21","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=53304","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\nThe many colours of molecular solar panels<\/strong><\/h2>\n\n\n\n![\"Shoreline](\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/AdobeStock_456172831-1-1024x673.jpeg\")
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\nWhy 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\nRhodopsins\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](\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/Hamburg_Profile_39-Kirill_Kovalev-1024x683.jpg\")
Kirill Kovalev is holding two syringes containing rhodopsin crystals. Credit: Kinga Lubowiecka\/EMBL. <\/figcaption><\/figure>\n\n\n\nCurrently, 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](\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2022\/11\/Hamburg_Profile_34-1024x683.jpg\")
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\nWhat 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](\"https:\/\/lh4.googleusercontent.com\/LBI5Z26n-LPdl-lzdkfxk33vOmjzKDuD8YVm_PyZGxcwDamUnbrO5qJWqOIV1R6gKVifsddx8IBK07IVn6of3rmLJ83b6Rri1n6E6vzP086A6yjUM1d5f3iZx9jtsa284rwXNiz0068wmk8BpKKd2art0eS77UZcGBaWwraA51H-D25s2nXo-x_dmFDHlutd15SbwA\")
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\nIn 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\nUsing light to hear better<\/strong><\/h2>\n\n\n\n![\"Photo](\"https:\/\/lh4.googleusercontent.com\/U1nOOPztUkfqQ5Uv3hW0l2yNDi5UZl16VnNTUq-VyCCR5048YtpE547YQce5T256pkTZArnjCNjQJXGa1qVx5OPUfJzuFBOfaqZPd_tAMDX9PRVr0Y8hjMcnulALV7CTxUD11G7iOpeJK0yp7_mRM5sGuZftzMMtxbXbl9yRpjqEbqbZJhDGBQXpL4iu6hZ0kq_jzQ\")
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\nKovalev, 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
At EMBL, Tosches took up work that Arendt had started as a postdoc when he discovered photoreceptor cells similar to those found in retinas, but in the middle of a Platynereis <\/em>larva\u2019s brain. She wanted to understand why they were there. Through a series of experiments, she discovered these cells are part of a larger group that produces melatonin, a chemical that essentially helps tell a body when it\u2019s time to sleep. In the case of the worm larvae, swimming and dispersing in the sea, the melatonin is used by these photoreceptor cells to sense when it is night or day so the worm larvae\u2019s swimming circuits can slow down during night. <\/p>\n\n\n\n \u201cThis work showed how the same molecule is used in animals that diverged from human\u2019s evolutionary path 600 million years ago, to do something very similar \u2013 controlling circadian rhythms of locomotion,\u201d Tosches explained. \u201cThe light-dependent control of locomotion is something that has existed since the beginning of the evolution of animal nervous systems. Other researchers discovered that even jellyfish sleep, and melatonin modulates or is involved in sleep mechanisms. This link between sleep and melatonin is something very, very ancient in animals.\u201d<\/p>\n\n\n\n In 2014, Tosches joined the group of Gilles Laurent at the Max Planck Institute for Brain Research as a postdoc. There, she used a single-cell approach to study the evolution of cerebral cortices in turtles and lizards, choosing them because they have the simplest cerebral cortex. <\/p>\n\n\n\n \u201cFor many decades, scientists have been comparing the brains of frogs, fish, turtles, and of course, mammals, and describing the neuroanatomy of these brains,\u201d Tosches said. \u201cBut what’s still obscure is how the differences<\/em> between these different vertebrate brains came about.\u201d<\/p>\n\n\n\n Additionally, Tosches has been interested in learning more about the cognitive capacities of vertebrates besides what has been gleaned from mice, primates, and humans. <\/p>\n\n\n\n \u201cAbout 320 million years ago, one vertebrate evolutionary line led to us mammals, and another led to reptiles and birds. And in these passing years, lots of changes happened,\u201d she said. \u201cEventually, mammals and birds acquired very high cognitive abilities independently. Birds are incredibly smart and have been studied more than other vertebrates with simpler cognition, which are not understood at all yet.\u201d<\/p>\n\n\n\n Since 2019, she has led her own research lab at Columbia University. With newts, Tosches uses genetic, genomic, developmental, and neurobiological approaches to investigate the evolution of brain cell types and neural circuits in the vertebrate brain.<\/p>\n\n\n\n \u201cWe are trying to understand whether salamanders can use landmarks to understand their location,\u201d she explained. \u201cA part of the brain involved in navigation, the hippocampus, has an innate ability to know where you are in space. We found that cell types there that help make this happen also exist in other species.\u201d<\/p>\n\n\n\n In early September, her research group and collaborators published a paper in Science<\/em><\/a> exploring the similarities and differences of neuron types in the forebrains of salamanders, turtles, lizards, and mice.<\/p>\n\n\n\n \u201cI am driven by curiosity,\u201d Tosches said, talking about the future of her research. <\/p>\n\n\n\n In five to 10 years, the EMBL alumna hopes to have created a complete, cell-by-cell description of how neural circuits are assembled and organised in a vertebrate brain. It\u2019s a \u2018dream that drives\u2019 her to think about her lesser-known Spanish ribbed newt Pleurodeles waltl <\/em>ultimately <\/em>being recognised as a model organism in much the same way that C. elegans<\/em> is extolled for its role in understanding neural circuitry.<\/p>\n\n\n\n And in the world of fundamental scientific research, that\u2019s a very big deal.<\/p>\n\n\n\n \u201cIf we look back at history, all the major breakthroughs in biology \u2013 and in science in general \u2013 came not because someone anticipated or planned for the societal impact or the impact on human health,\u201d she said. \u201cThat\u2019s the beauty of fundamental research. At the time many of these kinds of discoveries are made, nobody \u2013 not even the person who makes the discovery \u2013 is really aware of the influence they may have in future scientists\u2019 work or how the science can change how we think about and do things.\u201d<\/p>\n\n\n\n Tosches\u2019 determination to reach this goal is quite evident. Her voice only grows stronger as she shares more details from her current work. However, she is quick to add \u2013 more than once \u2013 that this drive not only comes from her parents but a culture of risk taking at EMBL.<\/p>\n\n\n\n \u201cWhat did I learn during my time at EMBL? Not to be afraid of trying new things,\u201d she said. \u201cYou are surrounded by people doing amazing science in so many different fields; it’s not like other institutes. The environment encourages you to talk to others even about things you yourself barely understand\u2026 you learn from each other.\u201d<\/p>\n\n\n\n She speaks of this experience as uniquely motivating, teaching her to \u2018dream big\u2019 and \u2018try new things\u2019. And her example of living this mantra comes in her own postdoc experience following EMBL. Upon learning of new sequencing technology available that could process thousands of cells at a time, she changed research direction, abandoning her original postdoc project to focus on a transcriptomics single-cell approach, finding herself ultimately \u2018more satisfied\u2019 in the new undertaking.<\/p>\n\n\n\n \u201cEMBL is very special, and consequently it has aspects impossible to replicate in a single research lab,\u201d Tosches said. \u201cHowever, what I am passing down to my students and postdocs is the idea of being fearless about the science they’re doing. We try new things every day because we’re working on a new system, a new animal, a new model. It\u2019s important to be positive \u2013 with the attitude of open-minded explorers who seize on new, unplanned opportunities and even find unexpected results.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":" Newts act as model organisms for Maria Tosches, winner of the 2022 John Kendrew Award, to further explore the cellular makeup of vertebrate brains.<\/p>\n","protected":false},"author":100,"featured_media":53974,"parent":0,"menu_order":0,"template":"","tags":[],"class_list":["post-53302","embletc","type-embletc","status-publish","has-post-thumbnail","hentry"],"acf":{"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":" Newts act as model organisms for Maria Tosches, winner of the 2022 John Kendrew Award, to further explore the cellular makeup of vertebrate brains.<\/span><\/p>\n","related_links":[{"link_description":"2022 EMBL Alumni Awards Winners announced\r\n","link_url":"https:\/\/www.embl.org\/news\/alumni\/2022-embl-alumni-award-winners-announced\/"},{"link_description":"EMBL Alumni Relations programme\r\n","link_url":"https:\/\/www.embl.org\/about\/info\/alumni\/"}],"source_article":false,"in_this_article":false,"press_contact":"None","article_translations":false,"languages":"","embletc_issue":[{"ID":53290,"post_author":"124","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"","post_title":"Issue 99","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"issue-99","to_ping":"","pinged":"","post_modified":"2022-11-17 11:34:48","post_modified_gmt":"2022-11-17 10:34:48","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc-issue&p=53290","menu_order":0,"post_type":"embletc-issue","post_mime_type":"","comment_count":"0","filter":"raw"}],"embletc_in_this_issue":[{"ID":53304,"post_author":"16","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"\n By Tom Furnival-Adams<\/em><\/p>\n\n\n\n As she reflects on her long, successful career, it is clear that Sara A. Courtneidge has always been driven, primarily, by an innate compulsion to discover how things work. <\/p>\n\n\n\n Growing up in Sussex, England, she recalls excitedly rushing to the butcher\u2019s shop on her way home one day to obtain a cow eye to dissect, having been shown the ropes by a particularly enthusiastic science teacher. She also remembers taking it upon herself to examine her family\u2019s tap water using a microscope borrowed from one of her brothers\u2019 chemistry kit. <\/p>\n\n\n\n And while these formative experiments ensured her family always boiled their water and thoroughly washed chopping boards, they also indicated early on Courtneidge\u2019s burning curiosity about the natural world that would shape the rest of her life.<\/p>\n\n\n\n It is this extraordinary will to examine and better understand crucial mechanisms of biology that led to her 2022 Lennart Philipson Award<\/a> recognising her major contributions to foundational and translational cancer research.<\/p>\n\n\n\n This could be perceived as her career coming almost full circle: Philipson was the Director General who recruited Courtneidge to EMBL in 1985. \u201cI had some fantastic interactions with Lennart; he was a wonderfully supportive man. I owe a lot to him,\u201d she said.<\/p>\n\n\n\n Courtneidge, who attended one of Britain\u2018s first comprehensive schools, attributes much of her early success to serendipity. She considers it a stroke of luck that she was taught by a PhD-level chemistry teacher, and was one of a handful of students in her year encouraged and supported to attend university. \u201cMy life has just been these series of fortuitous things,\u201d she said.<\/p>\n\n\n\n In 1972, she went to the University of Leeds, having \u201cannounced\u201d that she intended to do so to parents who were both slightly bemused by, and extremely supportive of, their daughter\u2019s boldness. She was only the second member of her family to attend university and believes that her undergraduate degree in biochemistry set her up for the rest of her career. \u201cIt was a really good basis for everything we understand about modern molecular biology now,\u201d she said.<\/p>\n\n\n\n Her PhD took her to the now-defunct National Institute for Medical Research in Mill Hill, London, where she specialised in virology and immunology. There she first encountered the role of T cells in recognising virus infection. <\/p>\n\n\n\n \u201cI was working within two labs, one led by an immunologist, and the other led by a virologist, using influenza virus genetics to study how the T cells interact with viruses. It's been interesting helping my friends and colleagues understand pandemics because we had a lot of conversations in my lab about pandemics and how you track them,\u201d Courtneidge recalled.<\/p>\n\n\n\n Courtneidge would have likely have continued down that path if not for one of her PhD advisors, the virologist Sir John Skehel, intervening. \u201cJohn said, you shouldn't do the same thing for your postdoc that you did for your PhD,\u201d she recounted. \u201cThis is a time to broaden your horizons.\u201d<\/p>\n\n\n\n Courtneidge began spending more time in the library, consciously following new, different trails of curiosity. She and Skehel discussed various scientific ideas at the lab bench all day long. That\u2019s how she settled upon cancer virus research.<\/p>\n\n\n\n With Skehel\u2019s endorsement, Courtneidge became interested in the recently discovered novel retroviruses, and he helped her decide to pursue this in one of the labs on the US West Coast. Having never flown before and having only been abroad once, she found herself on a plane bound for University of California, San Francisco to work with the respected microbiologist J. Michael Bishop.<\/p>\n\n\n\n Bishop was later awarded the 1989 Nobel Prize in Physiology or Medicine with Harold Varmus, with whom he discovered the first human oncogene, c-src<\/em> , which they were using to study cancer. Meanwhile, colleagues in the lab had just determined the protein that this particular oncogene made, c-Src. It had also just been discovered in another lab that the Src protein was a kinase \u2013 an enzyme that adds phosphate groups onto other proteins.<\/p>\n\n\n\n Courtneidge found she was one of the few scientists in the lab familiar with biochemistry and how to handle proteins. \u201cPeople were saying, \u2018Gosh, I wish there was a way we could find out where this protein is in the cell and what it does.\u2019 And I said \u2018this is something I know how to do\u2019,\u201d she said.<\/p>\n\n\n\n \u201cIt was an amazing time to work on oncogenes,\u201d Courtneidge said. \u201cNow we had this single protein that could turn a normal cell into a cancer cell. There was this push to work out how it does that. That\u2019s when I started working on Src in the lab.\u201d<\/p>\n\n\n\n After her PhD, Courtneidge returned to the National Institute for Medical Research. It had recently been discovered by scientists at the Salk Institute that a DNA tumour virus oncogene called middle T had some kinase activity associated with it \u2013 but they couldn't show that it was a kinase itself. Once again, she possessed the skills and knowledge in the right place at the right time: \u201cI had all the tools from working on Src and Alan Smith\u2019s lab at NIMR had all the tools for working on polyomavirus and the middle T oncogene.\u201d<\/p>\n\n\n\n Courtneidge collaborated with Smith and discovered that the Src protein binds to middle T protein produced by DNA tumour viruses when they infect the cell. That switches on Src activity that causes cancer. This major finding united two different research fields and paved the way for further developments.<\/p>\n\n\n\n \u201cGenerally, most DNA viruses just take the brake away [from cell cycle regulation). But the polyomavirus both takes the brakes away and expresses a very potent tumour virus oncogene which activates the accelerator. It was pretty clear at the outset that that was a fundamental reuniting of the tumour virus fields, which were split for a while, and it started a lot of other research,\u201d said Courtneidge.<\/p>\n\n\n\n In 1985, Courtneidge brought this research to EMBL, where she was, for a long period, the only female group leader. She later became EMBL\u2019s first female senior scientist. <\/p>\n\n\n\n \u201cIt's an intolerable burden on women to be the one example of a woman in a room because then, if you give a bad talk, it is generalised into \u2018women give bad talks\u2019,\u201d she said. \u201cIf your paper isn't well received, it\u2019s \u2018women's papers are inferior\u2019.\u201d Courtneidge has been a passionate and active spokesperson for gender equality in science throughout her career, believing better representation is key. <\/p>\n\n\n\n Courtneidge credits EMBL\u2019s multicultural environment for her insights into the many ways to approach research questions. She also recalls a \u201ccollaborative spirit and an open mindedness\u201d that fostered trust between colleagues and prioritised idea sharing above competition.<\/p>\n\n\n\n \u201cI have never had more than 10 people in my lab since EMBL,\u201d she said of the impacts EMBL has had on her approach. \u201cHaving a smaller lab helps collaboration; it's not just about how many papers you produce and doing your own thing.\u201d<\/p>\n\n\n\n After nearly 10 years in Heidelberg, industry called. <\/p>\n\n\n\n \u201cAt EMBL, we were publishing great papers, left, right and centre with wonderful people in my lab,\u201d she said. \u201cBut I reached a point where I asked, \u2018Is there more\u2019?\u201d<\/p>\n\n\n\n An opportunity in San Francisco caught her attention.<\/p>\n\n\n\n \u201cIf you want to develop treatments for people based on all the amazing scientific discoveries that were happening in the oncogene field, you had to apply that in some way. And I just thought: \u2018I need to put my money where my mouth is,\u2019\u201d she said.<\/p>\n\n\n\n Courtneidge joined SUGEN Inc. as Head of Research in 1994, where she guided novel kinase discovery and validation efforts in oncology, and developed the company\u2019s research operations. Her own research had to move to the backburner while she focused on the company\u2019s priorities, but Courtneidge has no regrets. She believes scientists should gain experience in both translational and fundamental research. <\/p>\n\n\n\n \u201cHow are you going to sell your research to a company if you haven\u2019t thought through what they\u2019d be interested in? What are the potential risks? What are the economics?\u201d she said.<\/p>\n\n\n\n Realising the day-to-day demands of business administration were leaving her little time for the scientific research she loved, Courtneidge ultimately returned to academia in 2001 to establish a lab at the Van Andel Research Institute in Grand Rapids, Michigan, focusing on applying fundamental research on how cancer cells move to identifying ways to interfere with metastasis.<\/p>\n\n\n\n She has since served as a professor and Director of the Tumor Microenvironment and Metastasis Program, and Director of Academic Affairs, at the Sanford Burnham Medical Research Institute, before joining Oregon Health and Science University in 2014, where she worked as an Associate Director of Translational Sciences for the Knight Cancer Institute.<\/p>\n\n\n\n Courtneidge\u2019s work over a number of decades has significantly contributed to understanding oncogene transformation, regulation, substrate selection, and function.<\/p>\n\n\n\n But Courtneidge is characteristically humble about her legacy. Instead of awards or accolades, she focuses on discoveries and new knowledge. <\/p>\n\n\n\n \u201cI want to leave a body of work and a toolbox for others to carry it forward,\u201d she reflected. \u201cI stood on the shoulders of giants, and I want everybody to keep climbing upwards towards better understanding\u201d.<\/p>\n","post_title":"From academia to industry and back","post_excerpt":"Sara A. Courtneidge, recipient of the 2022 Lennart Philipson Award, reflects on the fundamental and translational research aspects of her career in cancer research","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"from-academia-to-industry-and-back","to_ping":"","pinged":"","post_modified":"2022-11-16 12:38:21","post_modified_gmt":"2022-11-16 11:38:21","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=53304","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 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 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 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 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 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 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\nWhy evolutionary neuroscience is important<\/strong><\/h2>\n\n\n\n
Being \u2018fearless about your science\u2019<\/strong><\/h2>\n\n\n\n
The chemistry of serendipity<\/strong><\/h2>\n\n\n\n
Becoming EMBL\u2019s first female senior scientist<\/strong><\/h2>\n\n\n\n
Translational research and industry beckon<\/strong><\/h2>\n\n\n\n
The many colours of molecular solar panels<\/strong><\/h2>\n\n\n\n
Credit: Adobe Stock.<\/figcaption><\/figure>\n\n\n\nSwitching cells on and off with light<\/strong><\/h2>\n\n\n\n
Expanding the rhodopsin colour palette<\/strong><\/h2>\n\n\n\n
Rhodopsins in stop-motion<\/strong><\/h2>\n\n\n\n
Using light to hear better<\/strong><\/h2>\n\n\n\n