The European Molecular Biology Laboratory Magazine Issue 91 Summer 2018

Origins

Synapse Nibbling on brain cells Nucleus Ocean origins Cultures Seven new scientists Contents Synapse News stories

5 Belgian PhD student decodes DNA and wins a bitcoin

6 Commonly used drugs affect our 9 Wet-lab e-learning courses go live gut bacteria 9 Slovakia becomes EMBL member 6 New target could stop spread of state drug resistance 10 News in brief 7 How antibiotic resistance spreads 15 Captured: microglia nibbling on 8 Molecular cuisine for gut bacteria brain synapses

8 Synchronised waves control 16 Cambridge selected for Health Data Nucleus embryonic patterning Research UK site Feature stories

18 Ocean origins Cultures EMBL community stories EMBL alumna Èlia Benito-Gutiérrez on how her research and career evolved after searching the seas 32 Welcome to EMBL 36 The scientific origins of Edith Heard 22 38 Exploring genetic variation On the orchids of Darwin 39 PhD goals: why not start a company? 40 Humans of EMBL: Past lives How Darwin’s work revealed the intimate 44 Awards & honours relationship between orchids and insects Alumni 45 The EMBL launch pad

24 28 45 Harnessing alumni expertise The rise of GPU Mapping molecules computing in science on people, fields and 46 Powering up ATMs 48 Alumni award winners Discover how EMBL scientists are using A free, standardised 50 Twenty years of building teams GPU computing to push method is raising interest and sites biology forward in forensics, agriculture and microbiome studies 51 Guess who!

2 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 3 Contents Synapse News stories

5 Belgian PhD student decodes DNA and wins a bitcoin

8 Synchronised waves control 16 Cambridge selected for Health Data Nucleus embryonic patterning Research UK site Feature stories

2 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 3 MARIETTA SCHUPP/EMBL

Word to remember Belgian PhD student Microglia decodes DNA and wins Noun, pronunciation: /ˌm a ɪ k r əˈɡl ɪə / a bitcoin Microglia are immune system cells that keep the brain and PhD student Sander Wuyts won the DNA Storage Bitcoin spinal cord healthy by ‘eating Editorial up’ pathogens, dead and dying Challenge issued by EMBL-EBI’s Nick Goldman in 2015 neurons, and other cellular debris. Microglia also nibble Some of the most fascinating questions in science are about on synapses to strengthen origins. For biologists, perhaps the biggest question is: how did connections between neurons BY MARY TODD BERGMAN distributed DNA samples in test following a recipe. After one failed (p. 15). tubes. The first person to decode the attempt and an essential pause over life begin? But the history of life is also full of smaller origin The challenge DNA and find the ‘private key’ would Christmas, he worked tirelessly to stories – moments of biological innovation that each contribute On 21 January 2015 at the World win the bitcoin. put the data from sequencing into Economic Forum’s annual meeting the right order and decode the files. to the complexity of the living world. Publisher in Davos, Switzerland, Nick European Molecular Biology Laboratory Good timing In this issue, we follow an EMBL alumna’s rediscovery of an Goldman from EMBL-EBI described One week before the deadline, “I was extremely surprised and a new method for storing digital Sander Wuyts, a PhD student at the excited when the decoded files Managing editors elusive species in the Indian Ocean, which is providing key information in DNA. At the end of University of Antwerp and Vrije appeared, perfectly readable. There Edward Dadswell his talk, he issued a challenge. Universiteit Brussel, in Belgium, were the instructions on how to insights into the origin of animals with backbones (p. 18), and we Sonia Furtado Neves explore how the study of co-evolution had its origins in Darwin’s was the first to master the method claim the bitcoin, a drawing of James “Bitcoin is a form of money that and decode the private key, taking Joyce and some other things.” Editors observations of orchids and insects (p. 22). now only exists on computers, and possession of the bitcoin. Berta Carreño with cryptography, that’s something He revealed his uncertainty about Mehrnoosh Rayner EMBL is a place where many ideas and technologies have their we can easily store in DNA,” Its value on 19 January 2018: around whether his efforts would actually Emma Steer explained Goldman. “We’ve bought €9500. pay off: “Before participating in this origin or are further developed. We talk to our scientists about Oana Stroe a bitcoin for €200 and encoded its challenge, I had my doubts about the how GPU computing is revolutionising their research (p. 24), and information into DNA.” Goldman feasibility of such a DNA technology Design The contender report on a method for mapping molecules on surfaces (p. 28). Now completing his PhD in – but now I don’t.” Designyard microbiology – exploring the We delve into the scientific origins and current research of universe of bacteria through DNA Wuyts intends to sell his bitcoin and Printed by – Wuyts has the right balance of use the proceeds to invest in science EMBL’s next Director General, Edith Heard (p. 36), and EMBL ColorDruck Solutions passion, coding skills and great projects, thank the people who group leader Jan Korbel (p. 38). colleagues to tackle complex puzzles helped him, and celebrate earning Contact like Goldman’s DNA Storage Bitcoin his PhD in style. [email protected] Finally, we celebrate new beginnings: whether it’s Slovakia Challenge. joining us as a member state (p. 9), the company co-founded by Goldman, N et al. Nature, 23 January Cover illustration Wuyts saw Goldman issue the 2013. DOI: 10.1038/nature11875 EMBL-EBI PhD student Daniel Elías Martín Herranz (p. 39), Aad Goudappel challenge on YouTube back in 2015, or the seven new scientists who will head groups or facilities at SANDER WUYTS but it was a tweet about the deadline FULL VERSION ONLINE: EMBL (p. 32). We look forward to the new ideas and innovations NEWS.EMBL.DE in December 2017 – plus the skills he BIT.LY/embl-91-01 had acquired in the meantime – that that will follow. made him swing into action. READ SANDER'S BLOG POST ABOUT HOW HE DID IT: Edward Dadswell Sample of DNA in which one bitcoin Once he started, Wuyts became BIT.LY/embl-91-01b (and some other files) were encoded, Editor aware that decoding the bitcoin as posted to Sander Wuyts. wouldn’t be quite as simple as

4 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 5 MARIETTA SCHUPP/EMBL

4 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 5 Synapse How antibiotic resistance spreads

Commonly Resistant bacterium Non-resistant bacterium Transposon - Small piece of DNA that can change its position within a Plasmid - Loop of DNA Virus genome, or move from one DNA molecule used drugs to another

affect our IULIA CARTASIOVA/EMBL Antibiotics Non-antibiotic drugs Antibiotics kill non-resistant Non-antibiotic drugs sometimes gut bacteria bacteria have antibiotic effects

One in four drugs with human example by causing gastrointestinal growth of at least one species in targets inhibit the growth of side effects. the microbiome. These drugs cause Conjugation Transformation bacteria in the human gut antibiotic-like side effects and may A few commonly used non-antibiotic promote antibiotic resistance. Since drugs have recently been shown to many drug-microbe interactions are Transposons can come from the Bacterial cell dies and BY IRIS KRUIJEN cause changes in the composition likely to be specific to each person, bacterial DNA or from a plasmid breaks down, releasing its of the gut microbiome, but the these findings also open paths to contents The human gut contains a large full extent of this phenomenon personalised drug therapies aimed at number of bacterial species, was unknown until now. EMBL the individual gut microbiome. collectively referred to as the gut researchers led by Peer Bork, Kiran microbiome. In the past decade, Patil, Nassos Typas and Georg Maier, L, Pruteanu, M, Kuhn, M et al. it has become clear that the Zeller screened over 1000 marketed Nature, 19 March 2018. DOI: 10.1038/ composition of the gut microbiome drugs against 40 representative nature25979 affects human health. It is also well bacteria from the human gut, and known that antibiotics have a large found that more than a quarter of FULL VERSION ONLINE: impact on this microbiome, for the non-antibiotics affected the BIT.LY/embl-91-03 Bacteria connect temporarily. DNA from transposons or plasmids can be Transduction Another bacterial cell takes passed from one bacterium to another up plasmid or transposon DNA can sometimes be bacteria is transposons, or jumping KROLIK/EMBL ALEKSANDRA transferred from one New target could DNA: genetic elements that can bacterium to another switch locations in the genome by viruses stop spread of drug autonomously. When transferred resistance between bacteria, transposons can carry antibiotic resistance genes EMBL scientists unravel the within them. molecular basis of a major enables it to restructure the DNA, In a study published in Cell, Orsolya allowing it to insert its cargo – such mechanism of antibiotic Barabas and her group provided as antibiotic resistance genes – Transposons are incorporated into the Transposon is incorporated resistance transfer the first crystal structure of a into an extremely diverse range of bacterial DNA or into a plasmid (transposons into the bacterial DNA or protein-DNA machine that inserts bacteria. usually don’t exist independently) into a plasmid BY IRIS KRUIJEN transposons into recipient bacteria. Rubio-Cosials, A et al. Cell, 15 March

Bacteria have developed resistance The research team discovered that 2018. DOI: 10.1016/j.cell.2018.02.032 KROLIK/EMBL ALEKSANDRA to most of the drug compounds we the workhorse of the transposon use today. One of the major drivers insertion machine, the transposase FULL VERSION ONLINE: of resistance spreading between protein, has an unusual shape. This BIT.LY/embl-91-04

6 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE Synapse How antibiotic resistance spreads

affect our IULIA CARTASIOVA/EMBL Antibiotics Non-antibiotic drugs Antibiotics kill non-resistant Non-antibiotic drugs sometimes gut bacteria bacteria have antibiotic effects

6 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 9 Synapse embl-91-08 READ ONLINE: BIT.LY/ BY BERTA CARREÑO BERTA BY EMBL welcomed the Slovak Republic as its latest member state 29 January on 2018. The accession Slovakia of to EMBL membership emphasises the organisation’s commitment to promoting European science and collaboration among researchers. As a member state, Slovakia gains access to all EMBL’s of services and facilities. Its new status also allows Slovakia to Council,vote in EMBL’s the governing body that makes important decisions about the organisation. to Up two Slovakian delegates will join the Council, helping to shape futureEMBL’s programmes. Since Slovakia became an EMBL prospect member state in 2014, the ties between the two parties have become stronger: EMBL and Slovakia have applied for joint grants and contributed to joint publications. stimulate To collaboration with the Slovak research community, EMBL held a workshop at Comenius University’s Science Park in Slovakia,Bratislava, 2017. in Slovakia EMBL becomes member state THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE LABORATORY BIOLOGY MOLECULAR EUROPEAN THE embl-91-07 FULL VERSION ONLINE: BIT.LY/ [email protected]. EMBL’s free onlineEMBL’s courses are aimed at a range audiences, of from molecular biologists wanting to learn a particular technique to non-scientists interested in the latest discoveries and advances. They feature some of the cutting-edge research and new technologies used at the different EMBL sites, and build EMBL-EBI’s of success the on training online bioinformatics platform. like toIf a topic you’d see there’s covered in a new e-learning course, have you or expertise to contribute, get in touch with the e-learning team at: Optogenetics, which has been successfullyused in a diverse range of organisms, is introduced in one of the new e-learning courses. EMBL launches its its launches EMBL e-learning wet-lab first to introductions courses: and CLEM optogenetics CARREÑO BERTA BY EMBL has launched its firstonline courses focusingresearch on from laboratories at EMBL Heidelberg: An Introduction to Optogenetics and An Introduction to On-section CLEM (Correlative Light and Electron Microscopy). The courses combine different e-learning materials, ranging from how-to videos to interactive elements and exercises. courses More will become available in the coming months, covering other areas of EMBL expertise. Wet-lab e-learning live go courses

DANIEL KRÜGER/EMBL

ALEKSANDRA KROLIK/EMBL

, 22 February , 19 March, 19 2018. embl-91-05 embl-91-06 et al. Cell FULL VERSION ONLINE: BIT.LY/ FULL VERSION ONLINE: BIT.LY/ DOI: 10.1038/s41564-018-0123-9 DOI: developed a system that enabled toher synchronise the waves to an external rhythm. Strikingly, a new segment was made only when the andWnt Notch waves synchronised. Changing their relative timing prevented segment formation. K Sonnen, 2018. DOI: 10.1016/j.cell.2018.01.026 A recent Nature Microbiology article reports the on growth characteristics the of main human gut bacteria in 19 different growth media, with well-defined recipes. Peer Bork, Kiran Patil and Nassos Typas, all group leaders at EMBL Heidelberg, led the work. This resource provides scientists with tools to experimentally investigate gut microbiome ecology, helping them beyond go correlations to identify causes and effects. Tramontano, M, Andrejev, S et al. Nature Microbiology

formation new of segments are called and Wnt Notch. Both show periodic pulses activity, of which occur at the same pace as the formation the of segments. Scientists from the Aulehla and Merten groups at EMBL have shown that the timing between the two pathways’ waves is responsible for segmentation. At a specific time point, the and Wnt Notch waves synchronise and overlap, coinciding with the formation a new of segment. testTo what happened when the two waves were in not sync, the research team developed a new experimental strategy to control the rhythm and Wnt of Notch pulses. Katharina Sonnen, an EMBL postdoctoral researcher working in both the Aulehla and Merten labs, The bacteria living in the gut have a big impact our on health. But researchers still know don’t what kind food of most our of gut bacteria like to live on, precisely or how they metabolise nutrients.

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etc. In mouse embryos, two signalling pathways that are key to the During an journey embryo’s from a single cell to a complex organism, patterningcountless processes make sure that the right cells develop in exactly the right location and at the right time. Cells activate specificgenes rhythmicin a manner during this early development, resulting in waves activation of sweeping through the embryo. BY IRISBY KRUIJEN EMBL scientists importance the show in timing precise of embryosdeveloping EMBL BY IRISBY KRUIJEN EMBL scientists show how how show scientists EMBL a wide gut range of grow to lab in the bacteria Molecular cuisine for gut bacteria for cuisine Molecular

embryonic patterning embryonic Synchronised wavescontrol ALEKSANDRA KROLIK/EMBL 8 9 Synapse embl-91-08 READ ONLINE: BIT.LY/ BY BERTA CARREÑO BERTA BY EMBL welcomed the Slovak Republic as its latest member state 29 January on 2018. The accession Slovakia of to EMBL membership emphasises the organisation’s commitment to promoting European science and collaboration among researchers. As a member state, Slovakia gains access to all EMBL’s of services and facilities. Its new status also allows Slovakia to Council,vote in EMBL’s the governing body that makes important decisions about the organisation. to Up two Slovakian delegates will join the Council, helping to shape futureEMBL’s programmes. Since Slovakia became an EMBL prospect member state in 2014, the ties between the two parties have become stronger: EMBL and Slovakia have applied for joint grants and contributed to joint publications. stimulate To collaboration with the Slovak research community, EMBL held a workshop at Comenius University’s Science Park in Slovakia,Bratislava, 2017. in Slovakia EMBL becomes member state THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE LABORATORY BIOLOGY MOLECULAR EUROPEAN THE embl-91-07 FULL VERSION ONLINE: BIT.LY/ [email protected]. EMBL’s free onlineEMBL’s courses are aimed at a range audiences, of from molecular biologists wanting to learn a particular technique to non-scientists interested in the latest discoveries and advances. They feature some of the cutting-edge research and new technologies used at the different EMBL sites, and build EMBL-EBI’s of success the on training online bioinformatics platform. like toIf a topic you’d see there’s covered in a new e-learning course, have you or expertise to contribute, get in touch with the e-learning team at: Optogenetics, which has been successfullyused in a diverse range of organisms, is introduced in one of the new e-learning courses. EMBL launches its its launches EMBL e-learning wet-lab first to introductions courses: and CLEM optogenetics CARREÑO BERTA BY EMBL has launched its firstonline courses focusingresearch on from laboratories at EMBL Heidelberg: An Introduction to Optogenetics and An Introduction to On-section CLEM (Correlative Light and Electron Microscopy). The courses combine different e-learning materials, ranging from how-to videos to interactive elements and exercises. courses More will become available in the coming months, covering other areas of EMBL expertise. Wet-lab e-learning live go courses

DANIEL KRÜGER/EMBL

ALEKSANDRA KROLIK/EMBL

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embryonic patterning embryonic Synchronised wavescontrol ALEKSANDRA KROLIK/EMBL 8 CAMPBELL MEDICAL ILLUSTRATION

News in brief Synapse

Axon guidance From blood and bundling vessels to blood How stem cells are linked drugs Cells develop from stem cells. However, blood stem Rob Meijers’ group at EMBL Hamburg has found cells develop from vascular cells, which line the that axon guidance is more complicated than walls of our blood vessels. Christophe Lancrin’s affect was previously thought. During spinal cord group at EMBL Rome studies the transcriptional development, neurons have to project axons across regulation involved in this critical biological the midline to coordinate movements between process during embryonic development. Using the life the left and right sides of the body. Meijers’ group advanced bioinformatics analysis, Lancrin and discovered how a molecule that guides axons collaborators recently predicted that some of towards the midline (Netrin-1) works together with the transcription factors involved had opposing another molecule that drives axons to gather into activities. Essentially, two cell fates are competing and bundles (Draxin). with each other in one cell.

Liu, Y et al. Neuron, 1 March 2018. DOI: 10.1016/j. Bergiers, I et al. eLife, 20 March 2018. DOI: 10.7554/ death of neuron.2018.02.010 eLife.29312

FULL VERSION ONLINE: FULL VERSION ONLINE: proteins BIT.LY/embl-91-09 BIT.LY/embl-91-10 Proteins are responsible for countless activities in the cell. When reacting to external stimuli, stress or drug treatment, cells adjust Women in their protein levels. Scientists at EMBL and Cellzome have Science Day: developed a new technology, Information (arrows) emanating from chromatin to give rise to different cell types. called multiplexed proteome school event dynamics profiling (mPDP), to monitor the effects of Neus Martinez and Xavi Diego, drug treatments on protein members of the Sharpe group Chromatin usage reveals degradation and synthesis. at EMBL Barcelona, visited The tool allows scientists the Eulàlia Bota Primary to investigate protein School in the city to talk about developmental trajectories degradation mechanisms, women, science and curiosity Both cell type and developmental allows researchers to analyse all the their role in disease, and with 6-year-old children. The stage can be deduced from different cell types in an embryo at their modulation by drug objective of the event was to measurements of chromatin the same time and, importantly, at treatment. awaken future Albert Einsteins accessibility in thousands of single single-cell resolution. and Marie Curies in the audience cells. Researchers at EMBL and the Savitski, MM, Zinn, N, Faelth- CARLA MANZANAS/EMBL and to share the idea that anyone University of Washington, USA, Cusanovich, DA, Reddington, JP, Savitski, M et al. Cell, 15 can be a scientist as long as they used this approach to uncover how Garfield, DA et al. Nature, 14 March March 2018. DOI: 10.1016/j. are curious! cells in developing embryos regulate 2018. DOI: 10.1038/nature25981 cell.2018.02.030 their identity as they decide what FULL VERSION ONLINE: FULL VERSION ONLINE: FULL VERSION ONLINE: School visit to mark the 2018 International Day of Women and Girls in Science. kind of cell to become. This new BIT.LY/embl-91-11 and more systematic approach BIT.LY/embl-91-12 BIT.LY/embl-91-13

10 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 11 CAMPBELL MEDICAL ILLUSTRATION

News in brief Synapse

Liu, Y et al. Neuron, 1 March 2018. DOI: 10.1016/j. Bergiers, I et al. eLife, 20 March 2018. DOI: 10.7554/ death of neuron.2018.02.010 eLife.29312

10 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 11 News in brief Synapse

Jacques ERC Scientific Council New corporate Dubochet meets in Heidelberg partner for EMBL From 28 February to 2 March, EMBL and EMBO California-based company 10x Genomics, Inc., whose hosted the European Research Council (ERC) innovative Chromium™ System was listed as one donates Nobel Scientific Council in Heidelberg. More than 20 ERC of the top 10 innovations of 2017 by The Scientist, Council members joined ERC President Jean- has joined the EMBL Advanced Training Centre medal to EMBL Pierre Bourguignon to discuss topics of strategic Corporate Partnership Programme. Under the importance for the funding body. An open workshop programme’s auspices, 10x Genomics and EMBL will Jacques Dubochet, who was awarded stimulated exchange between ERC representatives serve a global community of investigators, providing the 2017 Nobel Prize in Chemistry, and the local life-science community on the advanced training in single-cell genomics and donated an official replica of his opportunities and challenges of applying for and transcriptomics at the Advanced Training Centre in Nobel medal to EMBL. The replica obtaining an ERC grant in the life sciences. Heidelberg. will be displayed when the EMBL Archive is inaugurated this summer. FULL VERSION ONLINE: FULL VERSION ONLINE: In the accompanying note, Dubochet BIT.LY/embl-91-17 BIT.LY/embl-91-18 states: “I am pleased to offer this ALEXANDER MAHMOUD ©NOBEL MEDIA AB 2017 AB MEDIA ©NOBEL MAHMOUD ALEXANDER copy of my Nobel medal to EMBL in testimony of my great thankfulness to an institution that, in my view, would deserve to be the laureate of the Prize.”

FULL VERSION ONLINE: BIT.LY/embl-91-14 Jacques Dubochet holding his Nobel medal during Nobel week.

The genetic risk New cryo-EM factors for depression service at EMBL EMBL-EBI Training JEFF DOWLING/EMBL Researchers at EMBL-EBI and collaborators have Heidelberg used robot avatars found that the genetic contribution to depression to help two new may differ between people who have experienced Scientists who want to obtain detailed structures mothers learn serious adversities in life and those who haven’t. of biological molecules now have a new facility about genomics. Results from this genome-wide association study to turn to: the cryo-electron microscopy (cryo- show that by removing people who have experienced EM) service platform at EMBL Heidelberg. major adversities from a cohort, researchers can get a The platform enables scientists from other For the first time, EMBL-EBI The technology, initially developed clearer view of the molecular mechanisms associated institutions to access state-of-the-art Using robot Training has enabled two students to help children with long-term with depression. microscopes for high-resolution data collection. to complete a course in genomics illness attend school, allowed the new Experts Wim Hagen and Felix Weis are on hand avatars in using robot avatars. The students are mothers to actively take part in wet Peterson, RE, Cai, N et al. American Journal of to support researchers with everything from healthcare professionals who have lab and bioinformatics modules just Psychiatry, 2 March 2018. DOI: 10.1176/appi. handling the microscopes to acquiring data at the recently had babies. From the comfort two weeks after giving birth. ajp.2017.17060621 highest possible resolution. bioinformatics of their home, each student controlled a 40 cm tall robot avatar located in FULL VERSION ONLINE: FULL VERSION ONLINE: FULL VERSION ONLINE: training class, which can transmit video, BIT.LY/embl-91-19 BIT.LY/embl-91-15 BIT.LY/embl-91-16 speak and even whisper to colleagues.

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FULL VERSION ONLINE: BIT.LY/embl-91-14 Jacques Dubochet holding his Nobel medal during Nobel week.

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Microfluidics technology developed company Velabs Therapeutics to EMBL spinoff at EMBL enables the rapid make a new microfluidics platform screening of antibodies, which can – based on the EMBL technology help in the development of new – available to the global antibody to help antibody therapies. Through its technology research community. transfer arm, EMBLEM, and with discovery the support of private investors, FULL VERSION ONLINE: BIT.LY/embl-91-20 Captured: EMBL has launched spinoff microglia LAETITIA WEINHARD/EMBL LAETITIA nibbling on brain synapses

Massive imaging study finds that Multiple synapse heads send out filopodia (green), which converge on one microglia (red), as seen by microglia strengthen synapses focused ion beam scanning electron microscopy.

VELABS THERAPEUTICS VELABS BY IRIS KRUIJEN

Around one-tenth of the cells in your brain are immune effective connectivity between neurons. As Weinhard EMBL spinoff Velabs Therapeutics system cells called microglia. Researchers have explained: “This shows that microglia are broadly will help antibody discovery. proposed that microglia pluck off and eat synapses involved in structural plasticity and might induce the – connections between brain cells – as an essential rearrangement of synapses, a mechanism underlying step in the pruning of connections during early circuit learning and memory.” refinement. But, until now, no one had seen them do it. Perseverance Loops, loops and loops: Stronger synapses The team recently published the results of this work – One-way crossing That is why Laetitia Weinhard, from the Gross group their first attempt to visualise this process in the brain – how DNA gets organised at EMBL Rome, set out on a massive imaging study which was the culmination of five years of technological to see this process in action in the mouse brain, development. Ultimately, by combining correlative Scientists have puzzled for decades over how across the midline in collaboration with the Schwab team at EMBL light and electron microscopy (CLEM) and light-sheet cells package more than two metres of DNA Heidelberg. “Our findings suggest that microglia are fluorescence microscopy – a technique developed at into tiny chromosomes while preparing for cell Andrew McCarthy’s group at EMBL Grenoble has nibbling synapses as a way to make them stronger, rather EMBL – the researchers were able to make the first division. EMBL researchers and collaborators solved a decades-long debate on a key process in brain than weaker,” says Cornelius Gross, who led the work. movie of microglia eating synapses. have finally managed to isolate and film the and embryo development. Using X-ray crystallography process, and have witnessed – in real time – and electron microscopy, the scientists describe the Warm welcome “This is what neuroscientists fantasised about for years, how a single protein complex called condensin structural changes resulting from the binding of the The team saw that in around half the cases where but nobody had ever seen before,” says Gross. “These reels in DNA to extrude a loop. By extruding neural receptor Robo with the Slit protein in humans. microglia contact a synapse, the synapse head sends findings allow us to propose a mechanism for the role many such loops in long strands of DNA, the Their findings demonstrate that correct guidance of out thin projections, or ‘filopodia’, to greet them. In one of microglia in the remodelling and evolution of brain cell packs its genome so it can be distributed the axons across the midline of the brain is triggered particularly dramatic case, 15 synapse heads extended circuits during development.” evenly between its two daughter cells. by a conformational change of the Robo receptor. filopodia toward a single microglia as it picked on a synapse. Weinhard, L et al. Nature Communications, 26 March 2018. Ganji, M et al. Science, 22 February 2018. DOI: Aleksandrova, N et al. Structure, 4 January 2018. DOI: DOI: 10.1038/s41467-018-03566-5 10.1126/science.aar7831 10.1016/j.str.2017.12.003 It turns out that microglia might underlie the formation of double synapses, where the terminal end of a neuron READ ONLINE: FULL VERSION ONLINE: FULL VERSION ONLINE: releases neurotransmitters onto two neighbouring BIT.LY/embl-91-23 BIT.LY/embl-91-21 BIT.LY/embl-91-22 partners instead of one. This process can support

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VELABS THERAPEUTICS VELABS BY IRIS KRUIJEN

14 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 15 17 Nucleus THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE LABORATORY BIOLOGY MOLECULAR EUROPEAN THE Delve into stories about the the about stories into Delve plants, and animals of evolution technologies and methods Diverse origins

AAD GOUDAPPEL embl-91-24 FULL VERSION ONLINE: VERSION FULL BIT.LY/ Harnessing data science data Harnessing “The volume health of data is already vast, and we have every reason to expect will it continue to grow quickly. must findWe effective, efficient ways to harness this data both for clinical research and practising medicine,” says Helen Parkinson, Head Molecular of Archival Resources at EMBL-EBI and Associate Director the of Cambridge HDR UK site. “We need a very broad range collaborationsof to ensure the data being collected and analysed is robust, precise andtranslatable. With a rich, connected ecosystem healthcare of data, we can support discovery by future generations scientists of and change healthcare the for better.”

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etc. EMBL Building experience on “EMBL-EBI believes data sharing is essential for improving our understanding human of health and disease,” explains Ewan Birney, Director EMBL- of EBI. “Contributing our expertise in data management and big data analysis to HDR UK is just way one we are supporting the biomedical of development informatics institutes across Europe and beyond. This is an exciting opportunity science for and public health, and we are pleased to be a part it. of Our experience with HDR UK will us help build the foundations interactions for with similar partners in other countries.” Health Data Research UK (HDR UK) has awarded £30 million to six sites across the UK to advanced apply data science to challenging issues in healthcare. The Cambridge site HDR of UK will be jointly run by the Sanger Wellcome Institute, the University of Cambridge and EMBL-EBI. The initiative hopes to unleash the potential data for and technologies to drive breakthroughs in medical research. The ultimate goal is to improve how we prevent, detect and diagnose diseases like cancer, heart disease and asthma. Research UK site for Health Data Data Health for Cambridge selected technologies for medicaltechnologies for research OANA BY STROE will unleash the potential of data and and data of potential the unleash will Jointly run by EMBL-EBI, the new site site new the EMBL-EBI, run by Jointly 16 17 Nucleus THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE LABORATORY BIOLOGY MOLECULAR EUROPEAN THE Delve into stories about the the about stories into Delve plants, and animals of evolution technologies and methods Diverse origins

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Ocean SILVIA ROHR

At first glance, they look like a cross between a been used interchangeably with another Benito-Gutiérrez fish and a worm and, in a sense, they are. They name, Asymmetron, making it unclear if the searching for don’t have a backbone, so can’t be classed as literature is always referring to the same cephalochordates. vertebrates, yet their notochord – a structure

ISTOCK animal. “One of our aims, when we first went made of a substance similar to cartilage, to the Maldives, was to find uncharacterised origins which runs the length of their thin bodies – cephalochordates such as Epigonichthys distinctly separates them from invertebrates. and describe their physical characteristics, EMBL alumna Èlia Benito-Gutiérrez on The calm waters of an This notochord can be described as a primitive as well as explore the information that their atoll, surrounded by backbone. In cephalochordates, it acts like genomes were hiding,” says Benito-Gutiérrez. how her research and career evolved after the Indian Ocean. a spine, sending out simple nerve signals With the advancement of different sequencing and supporting the body’s structure. It also techniques, these genomic secrets can finally searching the seas transiently exists in human embryos, acting to come to light. They have the potential to organise and develop our skull, spine and parts unlock some of the mysteries surrounding of the brain, but is broken down shortly before human origins and evolution. BY EMMA STEER birth. Searching the sand or Archimedes, the eureka moment made a major impact on Benito-Gutiérrez’s The notochord provides an important With this in mind, it’s easier to appreciate why came as he took a bath. For EMBL academic career. evolutionary link between cephalochordates Benito-Gutiérrez travelled thousands of miles alumna Èlia Benito-Gutiérrez, the and humans. It represents the transitional and braved searing temperatures to search for bath was a little bigger: she was on a Back in time period in evolutionary biology during which the cephalochordates. “Each day we sailed for Fboat in the Indian Ocean. Under the burning Benito-Gutiérrez’s journey began vertebrates and non-vertebrates split into three hours in a traditional Maldivian boat >> midday sun, Benito-Gutiérrez focused her while working at EMBL Heidelberg as a separate groups. Because cephalochordates portable microscope on the bizarre-looking postdoctoral fellow in the Arendt group. have changed very little in millions of years, creature again. From the asymmetrical During this time, she discovered a manuscript they’re an excellent model system to study – egg pouch, the striped spine-like structure from 1893 that pinpointed the last known not only for this physical characteristic, but running like a stack of coins along its length, location of a species in the Indian Ocean also for their genome. “There were distinct differences and the ever-intriguing mouth tentacles, it called Epigonichthys – an elusive sea creature seemed that she had discovered the mythical with an aptitude for hiding. Although Epigonichthys was discovered that made me realise this Epigonichthys. Lost for more than 100 years, more than 100 years ago, it has never been was something new. It was this elusive animal has still not been formally Epigonichthys belongs to a group of organisms described in detail. To confuse matters described. Yet its rediscovery is proving vital known as cephalochordates – small marine further, the name Epigonichthys has often incredibly exciting” for evolutionary biology research and has animals that burrow in the sand under the sea.

18 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 19 Nucleus

Ocean SILVIA ROHR

18 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 19 Ocean origins Nucleus SILVIA ROHR ÈLIA BENITO-GUTIÉRREZ SILVIA ROHR SILVIA ROHR

Benito-Gutiérrez >> called a ‘dhoni’ to reach the quiet atolls,” and the crew used handheld grabbing tools to Benito-Gutiérrez’s career itself evolved as she genome, we’re only seeing the end product,” Benito-Gutiérrez inspecting sand she explains. These secluded lagoons, enclosed reach into the water and carefully collect sand made the move from postdoctoral fellow to explains Benito-Gutiérrez. “If we understand on the dhoni boat samples from the by coral banks and surrounded by miles of from the sea bed. They then sieved it in search group leader at the University of Cambridge. the origin of our genome, we can better (above left) and in sea bed. choppy ocean, require great skill to navigate. of their live treasure. “In the beginning, we “It’s been an intense time these last couple of understand how our current genome works.” the lab at EMBL The local sailors, however, were happy to couldn’t find anything,” says Benito-Gutiérrez. years! But this exciting research is one of the For example, duplicate versions of our genes (above, top). help. “They’re amazing people,” says Benito- “It was very frustrating.” In fact, they sailed reasons I wanted to set up my own lab.” have arisen during evolution and taken up Cephalochordate Gutiérrez. “They were completely fascinated to 22 different GPS points before discovering different locations within our genome. Similar specimens to hear that they were so close to these living Epigonichthys. “When I first saw it, I thought Now Benito-Gutiérrez’s lab houses a giant duplications and gene rearrangements can (above). fossils. I learned afterwards that they were that, yes, this looks like a cephalochordate,” living ecosystem, which she and a dedicated occur in cancer, indicating that parallel having so much fun searching with us, that she explains, “but there were distinct team care for. “We can study and compare the mechanisms could be at play. they ended up doing a kind of lottery each day differences that made me realise this was genomes of three types of cephalochordates, to decide who would sail us out!” something new. It was incredibly exciting.” Yet which is something not many other groups The current plan for Benito-Gutiérrez is to considering how difficult it was to find these can claim,” she explains. “We’re quite sure continue researching this unusual creature Indeed, Benito-Gutiérrez went out on the boats creatures, their journey back to Heidelberg that they share a close common ancestor. and its hugely informative genome. As well many times, both during the day and at night. was relatively smooth. The Tara Oceans team What we’re currently unsure about is which as discovering more about the origins of the Upon arrival at their chosen locations, she scheduled a stop to collect the samples and cephalochordate is most ‘basal’ – the one that human genome and how it can go wrong, she bring them back to EMBL, alive and well. has remained most similar to the common hopes that confusions about the classification ancestor.” With the research carried out by of cephalochordates, which have arisen over the Tree of life Benito-Gutiérrez and her team, it might be past century, can also be unpicked. “There’s so It wasn’t until Benito-Gutiérrez had the time for a complete reconstruction of the way much still to find out,” says Benito-Gutiérrez. creatures in the lab that she began to realise cephalochordates are classified. “I don’t think the mystery surrounding “If we understand the origin how much potential this project had. “I set up Epigonichthys is solved just yet.” the lab at EMBL and looked after the animals Unravelling the genome of our genome, we can better myself,” she says. “We started sequencing This research might even provide insights READ ONLINE: understand how our current the Epigonichthys genome there, but after a into our own DNA, as it is likely that our BIT.LY/embl-91-25 while the project just became too much for genome has evolved from that of ancestral genome works” one person to manage.” Subsequently, in 2015, cephalochordates. “By sequencing the human

20 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 21 Ocean origins Nucleus SILVIA ROHR ÈLIA BENITO-GUTIÉRREZ SILVIA ROHR SILVIA ROHR

20 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 21 Nucleus On the orchids of Darwin How Darwin’s work revealed the intimate relationship between ISTOCK orchids and insects

BY ANDREA CERASE

Darwin’s any people know about Charles all served the same purpose: to attract insects studies of Darwin’s voyage on the Beagle to achieve this cross-fertilisation. As he ISTOCK orchids firmly and his detailed examination wrote in the closing chapter of Fertilisation established of the finches on the Galapagos of Orchids: “In my examination of Orchids, the idea that MIslands, which gave him crucial insights for hardly any fact has so much struck me as the The bee orchid, Ophrys apifera, has a lower petal many types developing his theory of evolution. It is less endless diversity of structure,—the prodigality that resembles the body of a female bee, and its of flowers are well known that Darwin spent a considerable of resources,—for gaining the very same end, flower produces a scent to match. pollinated by amount of time studying orchids, too. namely, the fertilisation of one flower by the insects. Fertilisation of Orchids was, in fact, the next pollen of another.” book he published after his famous On the Origin of Species. Tools of attraction insects. Some species have a labellum that is a proboscis nearly 30 cm long – something Orchids, unlike most flowers, have modified to such an extent that it looks like the Argyll described as “nothing but the vaguest Darwin’s studies of orchids began in asymmetrical petals. In particular, the back of a female insect, encouraging males to and most unsatisfactory conjecture”. England, not far from his home in Kent. modified lower petal, or labellum – Latin for try to mate with it. He was amazed and fascinated by the huge ‘lip’ – in orchids has evolved in a myriad of Such a moth was eventually found in variety of colours and shapes in this family shapes and colours. Darwin hypothesised that Mysterious moth Madagascar, but unfortunately not until 21 Examination of of plants. From painstaking observations, such variety was needed to attract different When Fertilisation of Orchids was first years after Darwin’s death. While Darwin a Madagascan meticulous dissections of local and exotic kinds of pollinating insects. He also suggested published in 1862, it was relatively well himself did not see this or many of his other orchid persuaded species, and field experiments, Darwin that some orchids have evolved special one- received by botanists and academics, but theories confirmed, his book on orchids Darwin that its concluded that orchids, unlike self-pollinating to-one relationships with their respective strongly criticised by proponents of natural represents an important part of his legacy. nectar must or wind-pollinated plants, relied on insects pollinators, rewarding them with nectar in theology such as George Campbell, Eighth It laid the foundations for another branch of be drunk by for pollination. He suggested that cross- exchange for their help with pollination. Duke of Argyll, who ridiculed Darwin’s evolutionary studies, co-evolution, which a moth with a

fertilisation – in which one plant is fertilised theories in his 1867 book, The Reign of Law. examines the way two or more species can proboscis 30 cm BY-SA 3.0) (CC ESCULAPIO by pollen from another – would increase We now know that only some orchids produce In particular, Argyll severely criticised one of have mutual effects on one another’s evolution. long. Such a a plant’s genetic fitness and provide the nectar, but all of them have found a way to Darwin’s predictions about the existence of an This remains a fascinating area of study for moth, Xanthopan diversity needed for natural selection, leading attract insects to spread their pollen. Some extreme one-to-one orchid-insect partnership. scientists around the world. morganii, was to evolution and the development of new orchid flowers attract insects with special After carefully examining an orchid from found living in species. He hypothesised that the mesmerising colours or patterns, while others use trickery, Madagascar, Darwin had concluded that READ ONLINE: Madagascar in combinations of forms and colours in orchids releasing sexual pheromones to ‘seduce’ it was most likely fertilised by a moth with BIT.LY/embl-91-26 1903.

22 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 23 Nucleus On the orchids of Darwin How Darwin’s work revealed the intimate relationship between ISTOCK orchids and insects

BY ANDREA CERASE

22 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 23 Nucleus The rise of GPU computing in science Discover how EMBL scientists are using GPU computing to push biology forward MIQUEL MARIN-RIERA, ANTONI MATYJASZKIEWICZ, PHILIPP GERMANN AND JAMES SHARPE/CRG AND EMBL AND SHARPE/CRG JAMES AND GERMANN PHILIPP MATYJASZKIEWICZ, ANTONI MARIN-RIERA, MIQUEL and although they’re not as flexible as CPU each GPU can do the calculation for that little The Sharpe cores, they can do one particular thing very, group.” Just as the image on a screen can be group at EMBL very fast: work out what your screen should divided up, so too can the model tissue. “Every Barcelona is display. cell has the same genome and every cell has to using GPUs to make the same calculations, that’s why it fits build agent- In computer games, every little region of so well into GPUs.” based models for the screen is the result of an independent morphogenesis, mathematical calculation that works out GPU software requires programming like this branching BY BERTA CARREÑO AND LAURA HOWES what that little bit of the screen should look languages with extra features that deal with sequence. like. You can do those calculations one by the parallelisation of the problem, such couple of years ago, researchers at run on graphics processing units (GPUs). The one, or you can divide the screen into lots as CUDA, but “programming and writing EMBL Barcelona did something resulting new software can run simulations of little bits, and do all the calculations in simulation software is similarly complicated quite radical. They threw away with hundreds of thousands of cells in a matter parallel. That’s exactly what the GPU is good whether you are running it on CPUs or their carefully crafted software of seconds on a single graphics card. The at: doing lots and lots of identical calculations GPUs,” adds Sharpe. It can be challenging andA started again from scratch. The reason, previous software would take minutes, hours simultaneously, with each one independent to find a programmer who can understand indirectly, was computer gaming. or even days to run. In the words of Sharpe, “It of the others. As computer game graphics the biological questions and then write the ended up fantastically well.” became more complex – from Spacewar to Call code, he notes. Sharpe says that there’s one “I had discussed it with my team on and off of Duty – so did GPUs. The problem of how to major benefit of this shift to GPU computing, over the past five years,” says James Sharpe, Graphical computation render the image from a computer game is split though: cost. A full-size CPU cluster costs a head of EMBL Barcelona. “But there is a lot of Open up any personal computer and you will into hundreds of thousands of little parallel lot of money and resources to run, he explains. effort involved in rewriting or writing a new find it packed with chips and components. calculations all done in a fraction of a second. “We have switched over to being able to simulation from scratch.” They include the central processing unit run everything in our own lab on our own (CPU), which does a lot of the heavy lifting “For us,” explains Sharpe, “it turns out that computers’ graphics cards. We will probably It took the right person to come along before and complicated processing, and the GPU the kind of calculation required for computer start using GPU clusters [racks of dedicated the Sharpe group could take the plunge. which quickly creates the images you see on games is similar to the kind of calculation GPUs] in the future. But, still, it’s saving a huge When Philipp Germann joined the group your screen – such as the ad in your Facebook we want to do. We try to simulate tissues and amount of time and money in this work.” as a postdoc, he played with the existing feed or the computer game you play at the end organs, how they grow, how their development software for a couple of months before of the day to relax. GPUs contain hundreds works. And similarly, if we have a tissue with Clusters of computation deciding to completely rewrite a multicellular or thousands of very specialised processors a hundred thousand cells, we can divide that In EMBL Heidelberg, the server room hums dynamics simulation, this time designed to called cores. These cores are small and simple, cell population into little groups of cells, and and flashes with computing power. Inside, >>

24 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 25 Nucleus The rise of GPU computing in science Discover how EMBL scientists are using GPU computing to push biology forward MIQUEL MARIN-RIERA, ANTONI MATYJASZKIEWICZ, PHILIPP GERMANN AND JAMES SHARPE/CRG AND EMBL AND SHARPE/CRG JAMES AND GERMANN PHILIPP MATYJASZKIEWICZ, ANTONI MARIN-RIERA, MIQUEL and although they’re not as flexible as CPU each GPU can do the calculation for that little The Sharpe cores, they can do one particular thing very, group.” Just as the image on a screen can be group at EMBL very fast: work out what your screen should divided up, so too can the model tissue. “Every Barcelona is display. cell has the same genome and every cell has to using GPUs to make the same calculations, that’s why it fits build agent- In computer games, every little region of so well into GPUs.” based models for the screen is the result of an independent morphogenesis, mathematical calculation that works out GPU software requires programming like this branching BY BERTA CARREÑO AND LAURA HOWES what that little bit of the screen should look languages with extra features that deal with sequence. like. You can do those calculations one by the parallelisation of the problem, such couple of years ago, researchers at run on graphics processing units (GPUs). The one, or you can divide the screen into lots as CUDA, but “programming and writing EMBL Barcelona did something resulting new software can run simulations of little bits, and do all the calculations in simulation software is similarly complicated quite radical. They threw away with hundreds of thousands of cells in a matter parallel. That’s exactly what the GPU is good whether you are running it on CPUs or their carefully crafted software of seconds on a single graphics card. The at: doing lots and lots of identical calculations GPUs,” adds Sharpe. It can be challenging andA started again from scratch. The reason, previous software would take minutes, hours simultaneously, with each one independent to find a programmer who can understand indirectly, was computer gaming. or even days to run. In the words of Sharpe, “It of the others. As computer game graphics the biological questions and then write the ended up fantastically well.” became more complex – from Spacewar to Call code, he notes. Sharpe says that there’s one “I had discussed it with my team on and off of Duty – so did GPUs. The problem of how to major benefit of this shift to GPU computing, over the past five years,” says James Sharpe, Graphical computation render the image from a computer game is split though: cost. A full-size CPU cluster costs a head of EMBL Barcelona. “But there is a lot of Open up any personal computer and you will into hundreds of thousands of little parallel lot of money and resources to run, he explains. effort involved in rewriting or writing a new find it packed with chips and components. calculations all done in a fraction of a second. “We have switched over to being able to simulation from scratch.” They include the central processing unit run everything in our own lab on our own (CPU), which does a lot of the heavy lifting “For us,” explains Sharpe, “it turns out that computers’ graphics cards. We will probably It took the right person to come along before and complicated processing, and the GPU the kind of calculation required for computer start using GPU clusters [racks of dedicated the Sharpe group could take the plunge. which quickly creates the images you see on games is similar to the kind of calculation GPUs] in the future. But, still, it’s saving a huge When Philipp Germann joined the group your screen – such as the ad in your Facebook we want to do. We try to simulate tissues and amount of time and money in this work.” as a postdoc, he played with the existing feed or the computer game you play at the end organs, how they grow, how their development software for a couple of months before of the day to relax. GPUs contain hundreds works. And similarly, if we have a tissue with Clusters of computation deciding to completely rewrite a multicellular or thousands of very specialised processors a hundred thousand cells, we can divide that In EMBL Heidelberg, the server room hums dynamics simulation, this time designed to called cores. These cores are small and simple, cell population into little groups of cells, and and flashes with computing power. Inside, >>

24 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 25 The rise of GPU computing in science Nucleus EMBL Balancing the users Just as microscopy technology has improved, so everything has scaled, requiring more and more computing power. But while it might seem intuitive that processing microscopy images, or modelling cells as if they were areas on a screen, could be suited to GPU computing, ESA PITKÄNEN/EMBL other teams have other uses for the HPC cluster – for example, using deep learning to process huge sets of data from cancer patients.

“Deep learning is a big buzzword and I’m also into it,” explains Esa Pitkänen, a postdoctoral fellow in the Korbel group at EMBL Heidelberg. “Graphics processing runs on linear algebra and while linear algebra is very Animation >> the High Performance Computing (HPC) That is hardly a surprise when you realise straightforward mathematics, you need to do a shows how a cluster serves scientists across EMBL’s sites that the microscopy image analysis that used lot of it. GPUs parallelise this computation on main memory to the GPU memory efficiently. EMBL Heidelberg deep-learning and packages up their different problems to be to take about 30 days to run on 250 CPUs a massive scale, and that happens to be exactly This means that developing the algorithms server room. model learns solved by a mix of CPUs and GPUs. now takes just 30 hours on a single GPU. And the same mathematics that you use to train for the GPU is getting more technical, which to recognise some of the largest users of the GPUs at EMBL deep neural networks. It’s very simple: it’s a in turn is now driving innovation. “I think sequence “When I came here, there were no GPUs Heidelberg are the microscopy facilities. “Only perfect fit.” programming for games is more exciting in patterns that installed,” explains Jurij Pečar, the engineer six years ago, we were still shooting film and the short term,” he admits. “But I’d rather underlie cancer who looks after the HPC cluster. “So I went we had to develop the film in the darkroom Pitkänen’s data is based on several thousand work on something that has at least the hope of mutations. around interviewing scientists to learn what manually,” recalls Wim Hagen of the Electron tumour samples, and the data he has is making the world a better place some time in they’d need. One of the main requests was Microscopy facility. “Develop, fix, wash, dry, multi-layered. “We have sequencing data, the future.” that they had software coming up able to use then scan the negatives and hope you didn’t methylation data, transcriptomics data, GPUs, so we invested in our first machine. As make a mistake. Good people could do three and then auxiliary and clinical data to top it Growing graphically people started using GPUs, they realised how boxes a day. Nowadays, it’s fully automated. We off.” Pitkänen is trying to get his program to Although computer games first drove the it speeds up their work and then, of course, we get 2000 to 3000 images a day and that pushes recognise patterns by letting the software development of GPUs, chip manufacturers had to buy more.” things.” learn how to recreate the data. In a sense, being are now optimising their GPUs for other able to recreate the data from a simple code applications, like Sharpe’s modelling or indicates that the code – a few numbers, for Pitkänen’s deep-learning applications. It example – captures the essential patterns in seems GPU-based computing is growing in the the data. It could be considered a more refined life sciences, and in the EMBL IT department. What is GPU computing? version of the suggested purchases we all get when we go internet shopping: people who have “There are parts of biology that are not so The central processing unit (CPU) The graphics processing unit makes calculations much faster this mutation here, and this attribute here, suited to GPU computing, like some tasks in is the ‘brain’ of a computer. (GPU) is a specialised component to perform and offers cost and also share similar tumour characteristics. To sequence-based informatics where you’re Its function is to carry out that was designed to handle power efficiencies. do that on CPUs, says Pitkänen, would take first uploading a huge dataset, and then slowly calculations that enable the graphics. Whereas CPUs have tens to hundreds of times as long. Instead, chugging your way through it,” concludes computer to run software. The from four to eight cores, GPUs GPU computing was initially he trained his model in two days. “The whole Sharpe. “But I believe in a certain version of CPU is split into processing consist of thousands of small developed for graphics-intensive process of training the deep neural networks systems biology – the approach in which you units, called cores, that receive cores that can handle many computational problems such is inherently massively parallel. And the way build computer simulations of a biological instructions, perform calculations, threads simultaneously. as 3D rendering and gaming, GPUs work is really well suited to train those process as a way of understanding the and take actions on these but is now being applied to a models,” Pitkänen explains. dynamical mechanisms of the system. Using instructions. The key power of the GPU computing is the application variety of domains including computers in this way – simulating dynamics CPU is its flexibility to multitask of GPUs to accelerate the CPU’s complex modelling, simulation Back at the HPC cluster, Pečar’s main [rather than analysing data] – is still quite rare, with many different types of jobs. computing by transferring and cutting-edge research – such challenge, he says, is working with the users but I expect and hope it will grow and become a It can perform tasks quickly but, compute-intensive portions of as the Sharpe group’s computer so that the big jobs from the microscopes can part of all biological projects.” like our conscious brain, can the code to the GPU, where simulations of mammalian limb run at the same time as other programmes focus on only a few ‘threads’ at a many threads can be handled in development. like Pitkänen’s. According to Pečar, GPU users READ ONLINE: time. parallel. For suitable tasks, this need to work out how to move data from the BIT.LY/embl-91-27

26 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 27 The rise of GPU computing in science Nucleus EMBL Balancing the users Just as microscopy technology has improved, so everything has scaled, requiring more and more computing power. But while it might seem intuitive that processing microscopy images, or modelling cells as if they were areas on a screen, could be suited to GPU computing, ESA PITKÄNEN/EMBL other teams have other uses for the HPC cluster – for example, using deep learning to process huge sets of data from cancer patients.

26 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 27 Nucleus Mapping molecules on people, fields and ATMs A free, standardised method is raising interest in forensics, agriculture and microbiome studies

BY IRIS KRUIJEN

hese glowing avatars are maps of made available in Nature Protocols. When the molecules. Every day, every inch of scientists first used this approach to map the skin on your body comes into contact molecules on the skin of two volunteers, they with thousands of molecules – from found traces of sun cream and other hygiene Tskin cream, sweat, and even the microbes that products – three days after they’d last been used. call your skin home. Now, scientists can create interactive 3D maps that show where each Having been approached by colleagues from molecule lingers on our bodies, thanks to a new fields as diverse as forensics, cosmetics, ecology method developed by Theodore Alexandrov’s and agriculture, the team has now converted team at EMBL and collaborators at the the method into a step-by-step technique and University of California, San Diego (UCSD), and intuitive software. THEODORE ALEXANDROV/EMBL ALEXANDROV TEAM/EMBL ALEXANDROV

Can you guess which four digits a volunteer spectrometry, so it’s unlikely someone would typed into this ATM? steal your PIN this way. But it does show nicely that we transfer molecules from our skin to If you guessed 1, 0, 7 and 8, you are right. The the objects we interact with – and that we can colour of the dots represents the amount of measure and map that. This has raised lots of a molecule that was transferred from the interest from forensics experts.” In previous person’s finger to the keypad. “There are much work, for instance, the scientists were able easier ways of stealing someone’s PIN,” says to make predictions about people’s lifestyles Alexandrov. “We first had to clean the ATM based on the molecules found on their mobile with methanol, then swab it and perform mass phones. >>

28 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 29 Nucleus Mapping molecules on people, fields and ATMs A free, standardised method is raising interest in forensics, agriculture and microbiome studies

BY IRIS KRUIJEN

28 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 29 Mapping molecules on people, fields and ATMs Cultures Cultures

32 Welcome to EMBL

36 The scientific origins of Edith Heard 38 Exploring genetic variation 39 PhD goals: why not start a company? 40 Humans of EMBL: Past lives 44 Awards & honours

Alumni 45 The EMBL launch pad ALEXANDROV TEAM/EMBL ANDALEXANDROV DORRENSTEIN TEAM/UCSD 45 Harnessing alumni expertise 46 Powering up 48 Alumni award winners 50 Twenty years of building teams and sites 51 Guess who!

>> The researchers used a sprig of rosemary this, scientists can study how plants transport collected on campus at UCSD to demonstrate molecules from old leaves to young ones, and that the method can be applied to agriculture. how they react to stress. Researchers could use the method to see if pesticides or other products sprayed on Protsyuk, I, Melnik, AV, Nothias, LF et al. Nature a field spread to neighbouring fields, and if Protocols, 21 December 2017. DOI: 10.1038/ they could identify patterns in that spread. In nprot.2017.122 this image, you can see that the old leaves at ADOBE STOCK AND EMBL AND STOCK ADOBE the bottom of the rosemary sprig have much READ ONLINE: higher levels of the flavonoid cirsimaritin than BIT.LY/embl-91-28 the newer leaves at the top. Using maps like

30 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 31 Mapping molecules on people, fields and ATMs Cultures Cultures

32 Welcome to EMBL

36 The scientific origins of Edith Heard 38 Exploring genetic variation 39 PhD goals: why not start a company? 40 Humans of EMBL: Past lives 44 Awards & honours

30 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 31 Cultures

Aissam Ikmi EMBL Heidelberg

We study the starlet sea anemone, Nematostella vectensis, to understand how developing multicellular organisms respond to changes in their environment while simultaneously Welcome executing their genetic program. Growing up in Morocco, I was addicted to science documentaries and fascinated by the way life was visualised at varying scales: from the level of individual cells up to whole organisms. When I went to France to do my undergraduate studies, I knew I loved biology. But it was not until I opened a developmental biology textbook and saw a picture of a normal-looking fly alongside a mutant fly that to EMBL had four wings instead of two that I knew I would become a biologist. I was hooked, Seven scientists start their labs at EMBL eager to understand how animals are built and how genes and other factors control their MARIETTA SCHUPP/EMBL BY BERTA CARREÑO, SARAH B. PUSCHMANN, EMMA STEER AND OANA STROE development and the genetic programs that give rise to the huge range of shapes that we see in nature.

The past few months have seen EMBL welcome seven FULL VERSION ONLINE: new group or facility heads. From sequences to sea BIT.LY/embl-91-30 anemones, their work spans a broad range of topics. We find out what keeps them inspired, motivated and dedicated. Sara Cuylen-Häring Maria Garcia Alai EMBL Heidelberg Sample Preparation and Characterisation Facility, EMBL Hamburg My lab is interested in the biophysical properties of chromosomes and other cellular assemblies that lack My team and I provide high-throughput crystallisation membranes – for example, the nucleolus. experiments to help users determine the biophysical characterisation of proteins. I’ve learnt that I really like I’m looking for people who are excited about the research the interaction with users, helping them design and set we’re doing in my group. Specific technical skills or up experiments. in-depth knowledge of chromosome biology are less important for me – these are attributes that can be Some of the users that come to the facility in Hamburg learned. But you cannot teach traits like passion for

are not structural biologists, so we provide them with JOANNA PIEPRZYK/EMBL research, curiosity or motivation. I like to work with support and supervision. At the end of the day, you feel young scientists who are eager to learn and are not afraid like you have done something useful and have helped of exploring completely novel techniques or research out – that’s something I enjoy. Some scientists prefer to directions. Cutting-edge science is never predictable, MARIETTA SCHUPP/EMBL have a big question and answer that. I like to see what and I like unconventional experiments. My philosophy is the puzzle looks like in the end too, but the truth is, I that any innovative idea is worth a try – even if it seems have so much fun with the methodology and applying crazy or unlikely to work. the technology. When designing these experiments, it’s important to focus on the problem that you want to solve. FULL VERSION ONLINE: FULL VERSION ONLINE: Keep it clear and simple, and it will be beautiful. BIT.LY/embl-91-29 BIT.LY/embl-91-31

32 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 33 Cultures

Aissam Ikmi EMBL Heidelberg

32 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 33 Welcome to EMBL Cultures

Arnaud Krebs Matthieu Boulard EMBL Heidelberg EMBL Rome

My group will be developing new approaches to further My lab focuses on epigenetics and tries to understand why understand transcription factors, which bind to DNA the genetic code can be interpreted differently by different ‘switches’ to regulate which genes get activated or cells or individuals. repressed. I hope to collaborate with other research groups here, I see this transition to group leader as an exciting including labs interested in completely disparate questions. opportunity to explore more scientific ideas and share I try to be creative and encourage imaginative initiatives the thrill of science. It’s going to be very enriching to in my lab. As is the case for musicians and painters, if develop projects with people in my lab: to plant a seed you want to move your field in a new direction, you have and see how it evolves. I think scientific ideas often to propose something new to your peers. Whether or not need to mature in order to reach their full potential, they accept it is a different question! The reality is that it’s and discussing with lab colleagues is, in my opinion, the difficult to achieve something without experiencing failure. fastest way to get there. It’s something that has had a But in the real world, we have to succeed at some point. One very strong impact on my career. I would advise young of the important and difficult challenges I face is to judge MARIETTA SCHUPP/EMBL scientists not to run to the next obvious thing; go for the amount of failure that is acceptable before I switch my PASCALE BEUDIN/EMBL something that really excites you. It’s certainly riskier – focus or change my approach. but totally worth it! FULL VERSION ONLINE: FULL VERSION ONLINE: BIT.LY/embl-91-34 BIT.LY/embl-91-32

Eva Kowalinski Virginie Uhlmann EMBL Grenoble EMBL-EBI

My team researches RNA editing, a processing step My group will help biologists get precise that diversifies RNA sequences by deleting, adding or information from their images by developing modifying parts of the RNA. analysis tools that blend mathematical models and computer vision algorithms. EMBL Grenoble is a lively European science hub. The site’s relatively small size encourages you to get out It’s important to keep sight of the bigger picture. of your bubble, seek collaborations, invite external We’re all working on very specific research speakers and look beyond the horizon. There’s definitely projects but should remember how they fit a special spirit about EMBL. The environment is open into the wider world of science. The way I and collaborative, and everyone gives stimulating input see it, all scientists are working together to to everyone else’s research. I want the people in my lab help understand our world. I’m hoping to find to be passionate about science and to love what they do. enthusiastic PhD students and postdoctoral I learnt from my own experience that there are times fellows that are as excited as I am about when everything goes well and the experiments are working at the intersection of biology, computer successful. But there are also periods when progress science and mathematics. This type of feels slow-moving, and that’s when you need to be interdisciplinary work isn’t an easy career path, MARIETTA SCHUPP/EMBL resilient – it takes willpower and passion. There are ups so ambition and a strong motivation are key!

and downs, so you have to love what you do and really DANIEL SAGE/EPFL want it. FULL VERSION ONLINE: BIT.LY/embl-91-35 FULL VERSION ONLINE: BIT.LY/embl-91-33

34 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 35 Welcome to EMBL Cultures

Arnaud Krebs Matthieu Boulard EMBL Heidelberg EMBL Rome

Eva Kowalinski Virginie Uhlmann EMBL Grenoble EMBL-EBI

and downs, so you have to love what you do and really DANIEL SAGE/EPFL want it. FULL VERSION ONLINE: BIT.LY/embl-91-35 FULL VERSION ONLINE: BIT.LY/embl-91-33

34 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 35 Cultures

The scientific originally intended to pursue a career in physics – she left university with a passion for genetics.

Fathoming silence The key epigenetic mystery that continues

origins of to fascinate Heard is the silencing of a CURIE HEARD/INSTITUT EDITH AND ATTIA MIKAEL chromosome that occurs in most female mammals. Usually, if a fertilised egg inherits an X chromosome from its mother and a Y chromosome from its father, it develops into a Edith Heard male. If it inherits an X chromosome from each parent, it develops into a female. But there’s a catch: having two functioning X chromosomes EMBL’s next Director General reflects on in the same cell can be fatal. Cells in females solve this problem in a the questions that drive her research seemingly simple way: they switch one X chromosome off – a process called X inactivation. But, as Heard has discovered through her investigations, nothing about disease because changing the 3D organisation In this image BY SARAH B. PUSCHMANN the way X inactivation works is simple. of the chromosome can disrupt normal gene of developing AND EDWARD DADSWELL During her postdoctoral work at the Pasteur regulation. cells, fluorescent Institute, Heard helped to narrow down the molecules reveal region of the X chromosome that acts as the Space for curiosity DNA (blue), master control centre for X inactivation. This Currently Director of the Genetics and part of the X hen Edith Heard was a child of X-inactivation centre produces a key player in Developmental Biology Department at the chromosomes about seven or eight, her father the inactivation process: a large RNA molecule Curie Institute in Paris, Heard will take up (red), and the sat her down at the kitchen called Xist (X-inactive specific transcript), the role of EMBL Director General in January Xist RNA (white). table in their London home which can associate with the X chromosome it 2019. She will go on tackling questions The green colour toW teach her some basic arithmetic. It wasn’t is transcribed from, triggering chromosome- about epigenetics and gene regulation, shows a region of long before she began asking questions: why wide silencing. since she plans to continue running her lab the cells’ nuclei do we count? How did the numbers we use get while working as EMBL Director General. called the nuclear chosen? Where did they come from? No one Heard’s work led to the unexpected discovery Looking ahead to that role, she emphasises lamina. around her knew the answers. “My poor father, that production of Xist requires regulatory the importance of supporting both applied just trying to teach me how to add – I think he DNA sequences – sequences that control the research – having clear applications in fields was at his wits’ end,” she says, smiling. She gene’s expression – which must be located such as medicine and industry – and research recalls lying awake at night, questions about at large distances away from it on the X that is more fundamental. “It’s important to the origins of numbers churning in her mind chromosome. Later, the hunt for these missing make space for curiosity-driven research, even long after her parents had gone to sleep. sequences by the Heard Lab, in collaboration when a tangible purpose isn’t immediately COURTESY OF EDITH HEARD with Job Dekker at the University of apparent,” says Heard. “We have learned again The questions that Heard has been unable to Massachusetts, led to the discovery of large, and again that basic research, when nurtured let go of in her adult life concern epigenetics: self-interacting regions of the genome that over time, leads to profound applications.” the study of changes in gene expression that they called topologically associating domains are stable, heritable, and reversible – without (TADs).1 This discovery opened up an exciting 1 Nora, EP et al. Nature, 11 April 2012. DOI: affecting the DNA sequence. A self-declared new area of research, as TADs are regions of 10.1038/nature11049 late convert to biology – Heard had her first DNA that often bring regulatory elements introduction to the field while studying Edith Heard will take up her role as EMBL Director General located on different parts of a chromosome FULL VERSION ONLINE: Natural Sciences at Cambridge, having in January 2019. into close contact. Disrupting TADs can lead to BIT.LY/embl-91-36

36 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 37 Cultures

The scientific originally intended to pursue a career in physics – she left university with a passion for genetics.

Fathoming silence The key epigenetic mystery that continues

36 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 37 Cultures Exploring PhD goals: why not genetic start a company?

Daniel Elías Martín Herranz biological mechanisms behind the epigenetic variation is in the third year of his PhD clock, a predictor of biological ageing. I’ve been exposed to an amazing community of researchers here, both on the computational MARIETTA SCHUPP/EMBL EMBL group leader Jan Korbel in Janet Thornton’s group at side at EMBL-EBI and on the wet lab side at reflects on his scientific origins and EMBL-EBI, but unlike other the Babraham. I’m incredibly thankful to my current research PhD students, he is also supervisor, Janet Thornton, for her support. starting a company Would you recommend this experience to BY EDWARD DADSWELL others? Absolutely! If you have ideas you want to BY OANA STROE explore as an entrepreneur, you should rowing up, the books Jan Korbel right people in my lab,” says Korbel. “It now definitely try it. You can do great science liked to read were standard feels very natural for us to combine the two Tell us about your start-up. and be an entrepreneur at the same time. childhood fodder: astronomy, approaches.” It all started with a conversation I had with Entrepreneurship gives you more freedom in dinosaurs and archaeology caught co-founder Thomas Stubbs, who was doing how you push things forward and teaches you Ghis imagination. It was only in his final years Shattering chromosomes his PhD in Wolf Reik’s group at the Babraham things that are also useful in academia. at school, when he started learning about Korbel’s research focuses on structural Institute. We had been working on the genetics, that an interest in biology really took variation in the human genome: that is, how epigenetics of ageing and wanted to explore FULL VERSION ONLINE: hold. our DNA rearranges – a process that has how we can use epigenetic data to predict BIT.LY/embl-91-38 implications for ageing and diseases including certain things people care about – effects of As an undergraduate, Korbel spent a few cancer. One area of study is a process the Korbel diet, exercise, stress, air pollution and so on. months as an intern at the Roslin Institute in group co-discovered, known as chromothripsis, One day, someone from RebelBio, the world’s Edinburgh, UK, at the same time that Dolly or ‘chromosome shattering’. In this process, first life sciences accelerator, contacted me on the sheep was in residence. “The experimental a chromosome undergoes multiple structural LinkedIn. RebelBio offers seed funding, lab research I pursued there inspired me,” he says. rearrangements in a single catastrophic space, mentorship and other helpful support “Later, this led me to study computational event. Korbel and his lab have been working for starting your own business. We joined As a cell prepares biology with a molecular biology angle. It to uncover the molecular processes by which forces with the other co-founders, fellow to divide, its was a fascinating and helpful time.” Both chromothripsis occurs. scientist Toby Call, and Charles Ball – an chromosomes computational and more traditional lab expert in marketing and sales – and that’s how (shown here in research now happen side by side in Korbel’s Korbel is now one of the leaders of the Pan- our company, Chronomics, was born. pink) condense, lab at EMBL. “I was lucky because I got the Cancer Analysis of Whole Genomes project, becoming more which aims to identify common patterns of What kind of service will you offer? tightly coiled and cancer mutations. At the European Association We want to use epigenetic data to monitor the easier to observe for Cancer Research (EACR) Congress in July, well-being and health of individuals over time under the he will receive the Pezcoller Foundation-EACR and help to improve them. We send people microscope. The Cancer Researcher Award (p. 44). “It’s a huge a saliva collection kit, sequence the sample, faint structure in honour for me, because it recognises the work process the information and give them access the centre is a cell of my group that started here at EMBL,” says to their results through our secure online nucleus in which Korbel. “It’s a very strong motivation for us to platform. the chromosomes continue pursuing this vital area of research.” are in their usual How has your work at EMBL-EBI decondensed FULL VERSION ONLINE: supported you in making this leap? state. BIT.LY/embl-91-37 In my PhD, I am trying to understand the KORBEL GROUP/EMBL EMBL

38 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 39 Cultures Exploring PhD goals: why not genetic start a company?

38 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 39 Cultures MARIETTA SCHUPP/EMBL

Humans of I’ve reinvented myself over the past EMBL: Past lives ten years I tell people I’ve had four or five careers so far! Over the Discover the journeys that brought people to EMBL past ten years, I’ve reinvented myself a number of times. As an employment counsellor, one of the biggest things BY EMMA STEER was helping students to find summer jobs, so helping with CVs, cover letters, application forms, interviews, etc. I think the most rewarding thing about that was FULL VERSION ONLINE: helping students find their first job and knowing that BIT.LY/embl-91-39 you’ve really helped someone with a skill that they’re going to use throughout their life. In fact, about five years ago, someone re-connected with me on Facebook after they got their first job. It was a very gratifying moment to know that you can have that kind of impact Iran in particular CORNELIUS GROSS on someone’s life. I also play the flute Andrew Hercules was a fascinating and bass guitar, but User Experience Designer, EMBL-EBI

country piano was always my RODICA PETRUSEVSCHI/EMBL This was something my parents wanted to do with me as a kid, in the 1970s. The idea was to favourite instrument drive to India, following the Silk Road. That was the tail end of people driving through Iran, I’m a classically trained pianist. I enjoy most Afghanistan and India. Then there was the musical genres, but my favourites are the Iranian Revolution. With American passports, Romantic composers like Liszt, Mendelssohn, we couldn’t go any more. Chopin and Tchaikovsky. I also play the flute and bass guitar, but piano was always my favourite This summer, with my wife and kids, we instrument. I started teaching piano when I took the classic Silk Route and went through was 17, mainly one-on-one, but when I came to eleven countries. The first day we entered Germany I also taught at the music school in a new country, everybody was anxious, but Heidelberg. I’m still in contact with one of my first fundamentally, I wasn’t that afraid. I was students here. She started learning to play piano curious. Iran in particular was a fascinating when she was 55. She taught me that it’s never country. I met an older man in the street too late to start something, and our lessons were there. His eyes were very… in Italian you’d say always full of laughter. Now she has become an ‘sveglio’; he was very awake. He was the only honorary grandma to my two children. She was the person I met who gave me some insights into first person at the hospital when my son was born the inner workings of Iran. He had seen how and she came and visited us all when my daughter things had changed with the current regime. was born too, so she’s really known them from the beginning! Cornelius Gross Deputy Head of Unit and Senior Scientist, Nicki Vegiopoulos EMBL Rome Marketing Manager, EMBL Heidelberg

40 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 41 Cultures MARIETTA SCHUPP/EMBL

40 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 41 Humans of EMBL: Past lives Cultures MARIETTA SCHUPP/EMBL MARIETTA SCHUPP/EMBL

There was an amazing feeling of I’ve always built, solidarity and unity sold and played When I lived in the Netherlands, I loved sports and didgeridoos organising sporting events. Then, when I moved to France, several French friends mentioned the Dutch I played didgeridoo for the first time at a birthday party Foundation Alpe d’HuZes. It’s this incredible event when I was 18, and that very same week I was like, “I that raises money to fight cancer. Each June, up to have to have one!” Since then I’ve always built, sold and 5000 people cycle, run or just walk up the Alpe d’Huez played didgeridoos. in France, up to six times in one day. That explains the name Alpe d’HuZes: ‘zes’ means six in Dutch. The trick is the circular breathing, where you’re pushing air out of your mouth and breathing in at As a volunteer, my main job was to liaise with local the same time so you have a continuous tone. The administrations and translate, but we also had a lot of longest I’ve been able to do it in one go was for an hour help from the local people. All sorts of people go up the and a half. I was playing with a pianist at a party in mountain, including people who have cancer and those South Africa and we were just playing and playing who have lost family or friends to the disease. I thought If you find something and playing. After a certain amount of time, you don’t they were never going to make it, but with the help of know what you’re playing or even if you’re playing. It’s the others, they did. There was an amazing feeling of you’re passionate only when you stop that you realise your lips are full of solidarity and unity. blisters. It was absolutely about, life changes Elise Bralet Justin Graham-Parker fantastic, such a Liaison Officer, EMBL Grenoble completely Kindergarten Assistant, EMBL Heidelberg magical moment I never loved training to be a chef, but I simply BERNARD CLOUET didn’t question it. I didn’t love school, but MARIETTA SCHUPP/EMBL I was the head of a musical theatre academy in South everybody told me you have to go to school, right? Africa for twelve years. We were called Stagedoor It’s not optional. No one ever said you have to be Academy, like the artists’ entrance to the theatre. Our passionate about what you’re doing all day long. students had decided musical theatre was the career Now, I’ve come to enjoy cooking and I still cook they wanted to pursue. a lot, but it’s different if you cook for yourself or for friends, compared to cooking in a restaurant. It was a very vibrant, creative and innovative In a restaurant, you’re just cleaning and peeling environment to work in, full of unexpected moments. potatoes. Then slowly you learn to cook. It’s a bit One colleague of mine, who was the opera singer and of an assembly line where you just pump it out. opera trainer, loved Japan and her experiences there. She was telling us about her trip to Japan when she It would have been the path of least resistance suddenly burst into song, singing this Japanese folk for me to just continue and not be happy. The song which she had learnt there. As it wasn’t an opera job makes you unhappy, but it’s just background song, I got to hear her normal singing voice, the one noise. If you can overcome that and find we seldom hear from opera singers. It was absolutely something you’re passionate about, life changes fantastic, such a magical moment and so different completely. from anything we had heard before. It was beautiful. Jonas Hartmann Roné Pawson PhD Student, EMBL Heidelberg Training and Development Officer, EMBL Heidelberg

THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 43 Humans of EMBL: Past lives Cultures MARIETTA SCHUPP/EMBL MARIETTA SCHUPP/EMBL

THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 43 Cultures PHILIPP ROTHE PHILIPP Alumni

EMBL The EMBL launch pad This edition highlights the paths that our alumni have taken from their EMBL origins. Alumni from the IT team reflect on how their experiences at EMBL have helped them take on leading roles within other multinational organisations (p. 46). We showcase this year’s talented winners of the John Kendrew and Lennart Philipson Awards (p. 48), and report that Nobel Prize winner and EMBL alumnus Jacques Dubochet has donated his Nobel medal to EMBL (p. 12). We also share Awards & honours how an EMBL alumna’s discovery in the Maldives led to her becoming a group leader at the University of Cambridge (p. 18). Finally, as Mark Green begins his retirement, he Theodore Alexandrov EMBL Director General-elect Edith Heard Lars Velten, a postdoctoral researcher in Lars reflects on his 20 years of service, as well as his biggest achievements, as Head of Administration at (centre) receiving was awarded the 2017 Inserm Grand Prix Steinmetz’s group, won the Otto-Schmeil-Preis the Chica und Heinz for her work in epigenetics. The annual prize for young researchers from the Heidelberg EMBL-EBI (p. 50). Schaller Research honours a scientist working in the French Academy of Sciences and Humanities in Award. research community whose work has led to Germany. Velten was awarded the prize To learn more about how EMBL shapes people’s paths, check this issue’s back cover for the next remarkable progress in understanding in the together with Simon Haas, a collaborator at the field of human health. Heard received the German Cancer Research Centre. EMBL alumni event near you. award at a ceremony on 30 November 2017 in Paris, France. EMBL-EBI Director Ewan Birney has been Mehrnoosh Rayner appointed as a new member of the UKRI- Head of Alumni Relations In December 2017, the Australian National BBSRC Council and will take up his University awarded Matthias Hentze appointment in April 2019. The Council is an honorary PhD “for his exceptional responsible for advising and making decisions contributions to science” at a graduation on scientific, research and innovation matters, ceremony in Canberra, Australia. Hentze as delegated to it by the UK Research and Harnessing alumni expertise received the traditional hood and certificate Innovation Board. before entertaining the attendees with a EMBL has always relied on the “Our volunteers are the cornerstone Human Resources and Finance speech on his career to date. In April 2018, EMBL Director General support of volunteers, such as of our strong alumni community. departments. The alumni network Iain Mattaj signed the National Academy of Scientific Advisory Committee They bring ideas and expertise, is helping with recruitment and In February 2018, Theodore Alexandrov Sciences’ registry of membership during the members, council delegates, expand networks and raise collecting best practices for specific was awarded the Chica and Heinz Schaller academy’s annual meeting in Washington, DC, advisors, ambassadors, event awareness around the world, making grant administration projects. Research Award for achievements in the USA. This follows Mattaj’s election as a foreign organisers, speakers, fundraisers our programmes both meaningful biomedical sciences at a ceremony at Heidelberg associate last year. and Alumni Association and relevant,” Papagiannis says. The Alumni Relations team are University for his pioneering work on the board members. To formalise, “When the IT team asked us to help identifying alumni with relevant metabolome (see p. 28 of this issue to read more In June, Jan Korbel will receive the Pezcoller communicate and strategically communicate the opportunities they experience for specific projects and about his work). Alexandrov also received an Foundation-European Association for expand the support that alumni can provide to IT professionals, it campaigns and may be contacting ERC consolidator grant for the METACELL Cancer Research (EACR) Cancer Researcher voluntarily bring to EMBL, the didn’t take long to find the perfect you soon. If you’d like to learn more, project this year, while Julia Mahamid, who Award for excellence and achievements in Alumni Volunteer Programme was ambassadors.” (p. 46) please contact Peter Papagiannis joined the Structural and Computational cancer research at the EACR25 Congress in set up, and Peter Papagiannis joined ([email protected]). Biology Unit in 2017, received an ERC starting Amsterdam, Netherlands. EMBL as Alumni Volunteer Officer The Alumni Volunteer Programme grant that began in 2018. in September 2017. is also working with the

44 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 45 Cultures PHILIPP ROTHE PHILIPP Alumni

44 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 45 Alumni Powering up

Alumni share how joining EMBL’s IT Mervi Lampinen team was a career upgrade Director IT, One IT Country Lead Germany

BY PETER PAPAGIANNIS MSD Sharp & Dohme GmbH

What did you enjoy most about IT platforms. This is a challenge, Francisco Lozano Alemany your role in IT at EMBL? but a great learning opportunity. Head of IT Services IT is an integral part of daily life at Also, the technical environment EMBL. Every newcomer – short- is very varied, which gave me the

International Agency for Research on Cancer, term or long-term – has to visit IT best opportunity to learn the latest LAMPINEN MERVI OF COURTESY World Health Organization for a user account, email address, technologies, before they were even computer and general IT support. commercialised. Developments Meeting this diverse group of surrounding the cloud, big data and people from all over the world – and other tools in this area are always What did you enjoy most about What made working in IT at having to use all my linguistic and first adopted and used at institutes your role in IT at EMBL? EMBL unique? technical skills to provide the best like EMBL. It was great that I could be involved The exposure to cutting-edge IT service we could – made it very in many different projects and technologies: top research relies on interesting. How did working at EMBL help in a broad range of technologies. top IT solutions. EMBL has a very your career path? Mervi Lampinen was at EMBL from 1994 to 1998. Managing the IT for an organisation good IT infrastructure as well as Also, due to the international EMBL offers learning and like EMBL poses huge technical regular training. The international make-up of EMBL, you have the development opportunities that What did you learn at EMBL? challenges, so it required our team environment also offers the chance opportunity to learn a lot from help you work both in industry and One should embrace EMBL’s short- to collaborate efficiently and to for personal growth – that was one of other countries and institutes by in academia. They helped me learn term contracts as an investment strongly support each other, which the first things I missed when I left. interacting with staff – this helps my strengths and my passion for IT in one’s career. It is an opportunity allowed me to learn a lot about you work in any country in the management. They also helped me to help you get to the next stage in topics for which I was not directly How did working at EMBL help world afterwards. I mostly enjoyed understand what kind of business your career. Many thanks, EMBL, responsible. I also enjoyed being your career path? the quick pace, the opportunity transformation is required to go for the wildest time of my life, in in contact with the scientists and EMBL helped me in three different to learn and develop, and the very from offline brick and mortar to both my professional and private asking them about their research, as ways: I learnt how a world-leading informal yet structured way of online. Working in an international life. It was the greatest learning I spent a lot of time in their labs. research centre functions from working. environment like EMBL made me experience ever! KATE LOZANO KATE an IT perspective, I gained an choose large multinational and incredible network of contacts, What made working in IT at international companies after LEARN MORE ABOUT EMBL'S IT Francisco Lozano Alemany was at and I enriched my CV for my next EMBL unique? leaving. SERVICES TEAM: EMBL from 1996 to 2005. career step. EMBL supports many different EMBL.DE/itservices

46 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 47 Alumni Powering up

Alumni share how joining EMBL’s IT Mervi Lampinen team was a career upgrade Director IT, One IT Country Lead Germany

BY PETER PAPAGIANNIS MSD Sharp & Dohme GmbH

46 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 47 Alumni Cultures

“I wanted to find the virus’s Achilles Alumni award winners heel and hit it with EMBL recognises the outstanding work of alumni antiviral agents” with the John Kendrew and Lennart Philipson Awards

BY BERTA CARREÑO A medical revolution Francesco’s work allowed hepatitis C to become the first case in the history of medicine Raffaele De Francesco’s work on the hepatitis in which a chronic viral infection was cured

HARVARD MEDICAL SCHOOL C virus (HCV) has led to a medical revolution. with direct antiviral agents. Previously, certain chronic viral infections clinical data sets with highly innovative were kept under control using drugs, but it Although the genome of HCV had been isolated contributions. “I use computer science to was never possible to cure them completely and sequenced, finding a cure for hepatitis build tools and visual interfaces that enable by removing the virus from the body. De C still presented a challenge. Liver cells are researchers to efficiently interact with difficult to grow in cell culture, and the virus biomedical data,” he explains. didn’t function as well in cultured cells as it does in the human body. It took more than a As a PhD student in the Brazma group at decade to find the right conditions to grow the EMBL-EBI, Gehlenborg worked on making virus in the laboratory. It was then necessary large collections of gene expression data to develop biochemical tools and assays that visually accessible so that biologists could would help researchers find ways of interfering discover patterns more easily. He is now with HCV enzymes – preventing the virus Assistant Professor of Biomedical Informatics from functioning. at Harvard Medical School, where he develops tools to visualise various types of data from In his lab at the Institute for Research in large-scale cancer genomics studies such Molecular Biology (IRBM) in Pomezia, as the Cancer Genome Atlas. Gehlenborg also Italy, De Francesco identified, purified tackles visualisation problems across scales and developed in vitro assays for two key as co-investigator of the 4D Nucleome Data viral proteins, NS3/4A protease and NS5B Coordination and Integration Center, funded polymerase. His discoveries allowed the by the US National Institutes of Health. With scientific community to start screening his team, he has created tools that allow for agents to inhibit the two viral enzymes, scientists to see patterns at the chromosome eventually leading to a cure for hepatitis C. Nils Gehlenborg, Big data to find new level, and then to zoom down to find patterns at who received the questions the level of DNA bases – the individual letters De Francesco explained that the huge John Kendrew of the genetic sequence. medical need pushed him to work with all Award, was a PhD For centuries, data visualisation has helped the molecular biology and biochemistry tools student at EMBL- (ITALY) GENETICS MOLECULAR FOR INSTITUTE NATIONAL EBI from 2006 to humanity identify patterns and gain new Gehlenborg’s lab is also exploring clinical available, to understand what each part of the 2010. insights. When London suffered a cholera applications of data visualisation using HCV genome does. “I wanted to find the virus’s outbreak in 1854, the English physician information from electronic health records. Achilles heel and hit it with antiviral agents.” John Snow used a map to trace the source “My long-term vision is that all the data of the infection to the water pump in Broad generated by clinical analysis, sensors and FULL VERSION ONLINE: Street, Soho. Now – in the era of big data – smartphones will be integrated,” he explains. BIT.LY/embl-91-40 visualisation is more important than ever. “Rightly visualised, this will help doctors diagnose and treat patients and will also help EMBL alumnus Nils Gehlenborg is advancing individuals understand how their health might Raffaele De Francesco, who received the Lennart the visualisation of complex genomic and be influenced by their behaviour.” Philipson Award, was a postdoctoral researcher at EMBL Heidelberg from 1988 to 1990.

48 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 49 Alumni Cultures

48 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 49 Cultures Twenty years of building Guess who! All these babies have grown up to become teams and EMBL group leaders. Test how well you know the EMBL community by guessing who they are!

sites ROBERT SLOWLEY/EMBL Mark Green, EMBL-EBI’s Head 1 2 3 4 of Administration, reflects on his time at the Institute

BY EMMA STEER After beginning his career at EMBL Heidelberg as the Internal Auditor, Mark “I think the biggest Green went on to become the first Head of Administration at EMBL-EBI. As he retires achievement has been to enjoy the next phase of his life, we catch a building teams, not glimpse of the personal highlights that defined Mark’s 20-year journey at EMBL. buildings” 5 6 7 8

How did you first start at EMBL? I started at EMBL Heidelberg as an internal home for bright ideas and the people who can auditor in 1997. It was a time of great turmoil make them happen. Lots of campuses have for me because I had just begun a relationship shiny new buildings, but few have people who with my wife-to-be a few days before being are as driven and collaborative as the ones you offered the job. For almost three years, we had find at EMBL-EBI. a long-distance relationship: she was in the UK, I was in Germany. That kind of thing was What are you going to miss? much more difficult back in the day before free The people and the intellectual energy in this roaming and all this social media malarkey. place. If you look at the arc established by When the opportunity of a shared role between Michael Ashburner and Graham Cameron, Heidelberg and Hinxton came up, I pretty carried on very much by Janet Thornton and

much leapt at it. The travelling between sites followed through by Rolf Apweiler and Ewan 9 10 11

Vladimir Benes Vladimir

continued until about 2003, when I finally Birney, the idea is to create an environment 11.

Wolfgang Huber Wolfgang

became full time at EMBL-EBI. where people work together. EMBL-EBI is a 10.

Evangelia Petsalaki Evangelia

community. It’s full of a cracking intensity of 9.

Iain Mattaj Iain

What have been your greatest interest and curiosity that brings out the best 8.

Alba Diz-Muñoz Alba

achievements? in people. 7.

Marco Marcia Marco

We built the EMBL-EBI East Wing and 6.

Maria Leptin Maria

the South Building, and we completely Based on an interview conducted with Mark 5.

Matthias Hentze Matthias

refurbished the Main Building. We Green by Lindsey Crosswell, Head of External 4.

Nick Goldman Nick

transformed the place and it took huge Relations, EMBL-EBI. 3.

Gerard Kleywegt Gerard

amounts of effort by a large number of people. 2.

Christian Löw Christian But I think the biggest achievement has been FULL VERSION ONLINE: 1. building teams, not buildings. EMBL-EBI is a BIT.LY/embl-91-41

50 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 51 Cultures Twenty years of building Guess who! All these babies have grown up to become teams and EMBL group leaders. Test how well you know the EMBL community by guessing who they are!

sites ROBERT SLOWLEY/EMBL Mark Green, EMBL-EBI’s Head 1 2 3 4 of Administration, reflects on his time at the Institute

much leapt at it. The travelling between sites followed through by Rolf Apweiler and Ewan 9 10 11

Vladimir Benes Vladimir

continued until about 2003, when I finally Birney, the idea is to create an environment 11.

Wolfgang Huber Wolfgang

became full time at EMBL-EBI. where people work together. EMBL-EBI is a 10.

Evangelia Petsalaki Evangelia

community. It’s full of a cracking intensity of 9.

Iain Mattaj Iain

What have been your greatest interest and curiosity that brings out the best 8.

Alba Diz-Muñoz Alba

achievements? in people. 7.

Marco Marcia Marco

We built the EMBL-EBI East Wing and 6.

Maria Leptin Maria

the South Building, and we completely Based on an interview conducted with Mark 5.

Matthias Hentze Matthias

refurbished the Main Building. We Green by Lindsey Crosswell, Head of External 4.

Nick Goldman Nick

transformed the place and it took huge Relations, EMBL-EBI. 3.

Gerard Kleywegt Gerard

amounts of effort by a large number of people. 2.

Christian Löw Christian But I think the biggest achievement has been FULL VERSION ONLINE: 1. building teams, not buildings. EMBL-EBI is a BIT.LY/embl-91-41

50 EMBLetc. SUMMER 2018 THE EUROPEAN MOLECULAR BIOLOGY LABORATORY MAGAZINE 51 September Upcoming meetings Events 3-7 Alumni

EMBL-EBI 1 July EMBL Course: Summer party, EMBL-EBI Structural Bioinformatics DANIEL RIOS/EMBL 19 July Inauguration of the EMBL Archive, EMBL Heidelberg

21 July Summer party,

September MORELLI/EMBL CHIARA AND CASTALDI LAURA BROWN, SAM September EMBL Heidelberg

5 October 10-18 29 EMBL in Finland, Biomedicum, Helsinki

EMBL Hamburg EMBL Heidelberg 8 October EMBO Practical Course: EMBO Workshop: EMBL in Spain, CBMSO, Membrane Protein Chemical Biology 2018 Madrid Expression, Purification and Characterisation

October October 2-5 15

EMBL-EBI EMBL Barcelona EMBL Course: Inauguration Symposium Introduction to Next Generation Sequencing

November November

VIEW THE COMPLETE 15-16 22-24 LIST OF EVENTS ONLINE: EMBL.ORG/EVENTS

EMBL Heidelberg EMBL Heidelberg EMBL Science and 20th EMBL PhD Symposium: Society Conference: Game Changers: Taking Life

Infectious diseases: Past, CORREIA/EMBL SANDRA Sciences to the Next Level Present, and Future