Leroy Hood: the Network of “Our Genome Excellence Comes Is Not Our to a Close Destiny” PAGE 8 PAGE 7

Home , Avram Hershko, Emmanuelle Charpentier, Fiona Watt, Leroy Hood, PITRM1

SPRING 2016

ISSUE 32

EMBO-India Partnership EMBO expands its global reach PAGES 2 – 3

Interview EpiGeneSys Leroy Hood: The network of “Our genome excellence comes is not our to a close destiny” PAGE 8 PAGE 7

Overview Biotechnology activities by Women in Science Cell biologist Feature From Parkinson’s Disease the EMBO Science Policy Programme Fiona Watt wins the 2016 FEBS | to ubiquitin – new findings by and report from the 2015 EMBO | EMBL EMBO Women in Science Award EMBO Young Investigators Helen Science and Society Conference Walden and David Komander

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www.embo.org NEWS

EMBO expands its global reach EMBC, EMBO and Government of India’s Department of Biotechnology sign cooperation agreement

nder the new agreement, India, as an are available,” commented Maria Leptin, Director associate member state, financially of EMBO. “We have been promoting Ucontributes to EMBC. In return, research- An official launch ceremony took place in Delhi international interactions beyond ers working in India will be eligible for the full on 4 February 2016, and the Nobel Laureates and range of EMBO’s programmes supporting talented EMBO Members Christiane Nüsslein-Volhard and Europe, and India is one of our researchers and stimulating scientific exchange. Ada E. Yonath joined a high-profile panel discus- prime partners. I am extremely The eligibility of these researchers will be evalu- sion. An EMBO-led delegation of ten research- ated against the same criteria as those from other ers is visiting various institutes across the pleased that India now is an states, allowing international exchange. country and meeting with Indian scientists and Associate Member and I look government representatives. The visit started in forward to India being able to Mumbai on 1 February and finished in Mohali “India can only succeed if we on 8 February. access EMBO activities.” partner with the best everywhere Maria Leptin, EMBO Director to bring the best here.” VijayRaghavan, Life sciences in India are developing fast, State Secretary, Government of India supported by governmental and academic initiatives to attract bright young people to science from inside and outside India. VijayRaghavan, EMBO has been steadily increasing interac- Secretary of the Department of Biotechnology tions outside of Europe during the past two for the Government of India, who signed the decades. This cooperation is the latest accom- agreement, said at the launch ceremony: “India plishment of EMBO’s Global Activities strat- is rapidly growing into a position where we are egy, which works to foster collaboration with making extraordinary demands on ourselves. scientists in non-European countries that show India can only succeed if we partner with the best strength in life science research. everywhere to bring the best here.” “We have been promoting international inter- The newly forged cooperation will build actions beyond Europe, and India is one of our upon already existing links between Indian and prime partners. I am extremely pleased that India European scientists. In 2015, ten Indian postdoc- now is an Associate Member and I look forward toral researchers received an EMBO Long-Term to India being able to access EMBO activities. Fellowship to work in Europe, and eight India- Many European researchers already have estab- Maria Leptin and VijayRaghavan based scientists received the EMBO Short-Term lished scientific connections in India. No doubt exchanging the signed Fellowship. A satellite symposium focusing on agreement at the launching these will be strengthened further once more research in India has been a part of the annual ceremony in New Delhi tools and formal opportunities for interactions conference, The EMBO Meeting.

Scientific lecture at the Global Biotechnology Summit following the launching event

EMBO delegation arriving at the National Institute of Immunology in New Delhi ©all pictures: Prasenjeet Yadav

Panel discussion with Matthew Freeman, Christiane Nüsslein-Volhard, Satyajit Mayor, Ada Yonath, VijayRaghavan and Maria Leptin

Though the EMBC was founded by its member scientists from Singapore have already joined Further reading: states as an intergovernmental organization to the Young Investigator Programme. “In addition, Official India-EMBO Partnership Symposium provide for cooperation among European States EMBO has cooperation agreements with South webpage: india.embo.org Website of the Department of Biotechnology / for life science research, EMBO as EMBC’s execu- Africa and with the Taiwanese Ministry of Science Government of India (including recordings of the tion body may expand its engagement with and Technology. Discussions are underway with scientific presentations and talks): further states outside Europe. After Singapore, other potential partner countries, particularly indiabioscience.org which signed a similar agreement in July 2015, elsewhere in Asia and in South America,” said Personal impressions and thoughts from EMBO India is the second country to acquire the status Anne-Marie Glynn, Manager in charge of EMBO’s Member James Briscoe: [thenode.biologists.com/ of EMBC Associate Member State. Four young Global Activities. far-india-europe/discussion/]

“Frontiers in cytoskeleton research: coordina- saw there,” recalls Janke. On this occasion, he tion, adaptation, fine-tuning” was the title of visited various research institutes in Bangalore, the three-day seminar. The meeting brought Pune and Mumbai and established contacts Indo-French together leading experts with different perspec- to local researchers. Together they decided to tives on cytoskeletal functions – in vitro as well set up a platform of exchange between French connections as in cells. The workshop turned out to be a and Indian group leaders and students. One high-level platform for intense and focused year later, Roop Mallik of the Tata Institute of EMBO Member Carsten Janke discussions, which “will certainly result in Fundamental Research in Mumbai and Aurnab active research collaborations and joint grant Ghose of the IISER Pune teamed up with Janke initiates a cytoskeleton seminar proposals in the future,” Janke is convinced. to submit a workshop proposal to the French- in Pune The 20 participating group leaders talked Indian exchange program CEFIPRA, which about novel frontiers to be addressed in future promptly selected it for funding. and how these challenges can be mastered “France has never been closer to India,” by combining complementary expertise and tweeted EMBO Young Investigator and speak- MBO engagement in India has gone a knowledge in interdisciplinary research. er Manuel Thèry on the second day of the long way and builds upon many already cytoskeleton seminar. There are already plans Eexisting links between Indian and The idea for the workshop was born in for a follow-up conference – this time on European researchers. One example is a confer- 2013, during an EMBO-India Bioscience meet- French territory. ence on cytoskeleton research that took place ing that was held in Bangalore and organized in Pune last October co-organized by EMBO by the EMBO Young Investigators Programme. www.iiserpune.ac.in/events/Indo-French+ Member Carsten Janke of the Institut Curie in “It was my first visit to India. I was thrilled by Conference+on+Cytoskeleton+Research France. the great institutes and the high-level science I

©2016 EMBO EMBOencounters | Spring 2016 | [email protected] 3 gene therapies. Gene-transfer efficacy and safe- th EMBO | EMBL ty have long been the major problems for gene Science and Society therapy, but Naldini’s team has developed new techniques that seem to have overcome these conference problems and recently produced results in two clinical trials for the treatment of rare diseases in children, raising hopes and expectations of cures for devastating genetic diseases. In this area there is often a tension between patients, their families, scientists and doctors, who are eager to test research advances in the clinic as soon as possi- and ble to treat some otherwise lethal diseases, and regulators, who, in order to protect patients, take a cautious approach and often impose controls he conference Emerging Biotechnologies: concerns both inside and outside the scientific that are thought to delay progress. Hype, Hope and Hard Reality focussed on community. These concerns relate in particular In the session about biotechnologies and the Tthe social impact of innovative biotechnol- to its potential use in editing the human germ- environment, Anne Osbourn, project leader at ogies, particularly in the fields of human health line, resulting in changes being passed on to the John Innes Centre in the UK, talked about and the environment. An interdisciplinary and future generations. More research is needed to the fantastic contribution of plants to impor- international group of 17 speakers and about 200 prove that the technology is safe and that genome tant pharmaceutical and industrial products. participants from Europe and beyond gathered edits occur in the desired position. Moreover, the Biotechnology has opened many alternative for two days in the auditorium of the Advanced possible application of CRISPR-Cas9 to germ-line routes in the production of plant products. A Training Centre in Heidelberg last November. The editing has revived international ethical and poli- well-known example is artemisinin, an anti- discussion topics included the roles and respon- cy discussions about whether research involving malarial drug that is naturally produced by sweet sibilities of stakeholders in realising the potential the human germ-line should be allowed at all, wormwood. Using synthetic biology techniques, economic and societal benefits of these technolo- and about the roles and responsibilities not only scientists have succeeded in producing synthetic gies; issues such as governance, ownership, and of scientists, but of many other social groups, in artemisinin from yeast in much higher quantities innovation were also discussed. taking decisions on the use of this technology. and at lower prices than that derived from tradi- Modern medical biotechnology is the most Luigi Naldini, Director of the San Raffaele tional cultivation. widely applied area of biotechnology and a Telethon Institute for Gene Therapy in Milan, number of talks were dedicated to it. The speak- presented his work which uses a novel combina- The talks and slides from the conference are ers on this topic illustrated the potential benefits tion of old technologies, stem cell therapy and available at: http://events.embo.org/science- of these applications for patients as compared gene therapy: the development and application society-conference/online-talks.html to existing therapies, and highlighted their limi- of HIV-based vectors to deliver blood stem cell tations and the challenges of bringing them to the market. The range of applications presented was very broad, ranging from CRISPR-Cas9 (Dirk Heckl), to stem cell and gene therapy (Luigi Naldini), tissue engineering (Paolo de Coppi), Biotechnology work by the EMBO and genetic modification of mosquitoes to fight dengue fever (Simon Warner). Another session, dedicated to biotechnolo- Science Policy Programme gies and the environment, included talks on synthetic biology (Sven Panke), bioremediation here are many concerns that arise from scientific and governance gaps in the use of (Victor de Lorenzo), the production of plant biotechnology applications. Some of human genome data intentionally made iden- natural products and new-to-nature chemicals Tthem are old, like the ethical issues tifiable for research purposes. Main questions (Anne Osbourn), and the use of genetic markers related to modifying the human germ-line or were: 1) How much phenotypic and medical to monitor and possibly restore animal species the potential environmental impacts of intro- information do researchers need in order to (Carsten Nowak). ducing new plant varieties. But the continu- extract useful data from genomes? 2) What ous advances in scientific knowledge and does the consent process look like for making Some highlights from the conference the ever more refined technologies available genome sequence publicly available? 3) How The recently developed CRISPR-Cas9 technology have opened new possibilities for a growing much interpretation of data do researchers for gene editing was a focus of the conference. number of scientists to develop new products owe to research participants? 4) How would Dirk Heckl from the Hannover Medical School with more ease. EMBO, among other organiza- “misuse” of genetic information be identified in Germany presented and discussed the many tions, is monitoring these developments, and and punished? potential applications of what has been defined aims at ensuring that science is carried out for The report is available at: as the game changer in genome editing. Due to its the benefit of society. www.embo.org/science-policy/ simplicity, efficiency and low cost, the CRISPR- As an example of EMBO’s interest in biotechnology-and-genomic-technologies Cas9 system can be used in all fields of biomedi- developments in biotechnology, the Science cine, from basic research to clinical applications. Policy programme organized in December Recent activities: Moreover, in agriculture, CRISPR-Cas9 can be 2014 an exploratory workshop, supported ➔➔ Brocher Foundation-supported workshop used to modify crops without combining DNA by the European Science Foundation, on on The genomics of human cognition and from different species, potentially putting an end The use of non-anonymized human genome psychiatric disease, 7 – 10 December 2015 to public concerns that mixing DNA of different sequence in research: Science and policy. ➔➔ ESF-supported Workshop on the Use of species will have undesirable consequences. The interdisciplinary group of participants non-anonymized human genome sequence in Along with the enthusiasm about its poten- evaluated current knowledge and revealed research, 10 – 11 December 2014. tial, CRISPR-Cas9 genome editing has also raised

stem cells. She was one of the first to discover that processes such as inflammation, physical forces and epigenetics influence skin stem cell behaviour. The award winner was also recognized for her commitment to gender issues, her leadership qualities and her active mentorship of junior scientists. In a series of interviews she held with 24 female scientists she exposed the barriers and challenges that women who pursue a career in science face. The interviews were published in the Journal of Cell Science, for which she served as Editor-in-Chief for almost a decade, until 2011. The stem cells expert also played a key role in promoting the British government’s investment in stem cell research. “Her research continues to be at the cutting edge,” said Brigid Hogan of the Duke University Medical Center in Durham, United States. “She has boundless energy and enthusiasm, and in ©Centre Medicine London for Stem Cells and Regenerative her leadership positions she has worked tirelessly to build interactive and collaborative research ver since she was a child she knew that Much of Fiona Watt’s work has focused on the communities.” she wanted to be a scientist: dressed in stem cells of mammalian skin and the molecu- The 2016 FEBS | EMBO Women in Science Ea child’s lab coat she used to play with a lar and genetic pathways that work together to Award of 10,000 Euros will be presented to Fiona chemistry set and keep pet newts. “Like many control epidermal stem cell proliferation and Watt on 6 September at the FEBS Congress in scientists I could not conceive of being anything differentiation. She has made numerous funda- Ephesos/Kusadasi, Turkey, where she will give a else,” she says. Today, Fiona Watt is Director mental discoveries, most recently about how special lecture. of the Centre for Stem Cells and Regenerative the epidermis interacts with different classes of Medicine at King’s College London and looks dermal fibroblasts, and how these normal signal- To find out more about the award and Fiona back at a successful career that spans more than ling mechanisms go awry in cancer and skin Watt’s career steps see press release at: http:// 35 years. In February, she was announced winner disease. embo.org/news/press-releases/press-releases- of the 2016 FEBS | EMBO Women in Science Over the past few years, the British biologist 2016/2016-febs-embo-women-in-science-award Award for her achievements in epidermal cell has focused on using new technologies to under- biology and epidermal stem cells. stand what controls the fate of human epidermal

Unravelling synthetic biology

ynthetic Biology Course”, managed by iBiol- “ ogy in collaboration with EMBO, is a series Sof online talks launched last January (see also EMBOencounters Summer 2015). It covers Victor de Lorenzo general principles, technical challenges, current speaking about research and ethical issues in synthetic biology synthetic biology research. The series was linked to the EMBO on iBiology.org Practical Course “Synthetic Biology in Action” ©EMBO/iBiology that took place in Heidelberg last June. The very first lecture was given by Victor have been recorded with more than 5,000 down- To watch all lectures go to: www.ibiology.org/ de Lorenzo of the Spanish National Centre for loads. De Lorenzo’s talk – next to Timothy Lu ibioeducation/taking-courses/synthetic-biology- Biotechnology. He answered basic questions and Jan van der Meer – are the most popular course.html about what is synthetic biology and how it relates ones. The lectures were recorded at EMBL in to other areas of biology. So far, eighteen lectures Heidelberg.

applications developed at Stanford. In addition Life Science Alliance between to a strong expertise in basic science, Stanford is a leader in clinical applications and engineer- EMBL and Stanford ing technologies. These could be brought to the EMBL system and disseminated through the core Inspired by his dual affiliation, EMBO MemberLARS STEINMETZ initiates facilities to the European audience via EMBL’s a new transcontinental collaboration kicked off at the Personalised Health infrastructure. The Personalised Health Conference will be Conference at EMBL. repeated in Stanford in two years. In parallel, there will be conferences in structural biology ou can’t list your iPhone as your primary- and biological imaging. “ care physician,” reads the caption to a “We hope we can impact healthcare in the next Yrecent New Yorker cartoon. Yet this is not 10 – 15 years,” said Lloyd Minor. He has made such a distant vision as we might think. Today precision health a focus of the Stanford School a smartphone can measure sleep patterns. Many of Medicine. “What we hope to do in precision people carry external sensors to measure pulse health is to create a delivery system and path- and physical activity. “In the future we will prob- ways of care that are predictive and preventive.” ably have thousands of biosensors on our body The transition will not happen over night though. that register information about various molecular There have been changes with more precise treat- parameters to deliver better, more personalised ment, in cancer for example, but those are still care,” predicts Lars Steinmetz. the exception rather than the rule. Steinmetz is Professor of Genetics at Stanford Yet the field has already come a long way. University School of Medicine, Co-Director of Today even governments have ushered in a the Stanford Genome Technology Centre and change: in the United Kingdom, Genomics Associate Head of the Genome Biology Unit at England launched the 100,000 genomes project EMBL. He was the initiator of the firstEMBL | last year. In the United States, President Obama Stanford Joint Conference that took place at EMBL and the White House have announced a preci- in November 2015 and focused on personalised sion medicine initiative, which involves a cohort health. The meeting brought together scien- of one million individuals. Keynote lecturer tists, clinicians, patient advocates, funders and Lee Hood of the US-based Institute for Systems ethicists discussing the progress and promise of Biology explained the concept of Transforming personalised health. Healthcare through Wellness in his talk (see also “We had a meeting on -omics and precision interview next page). Major governments are health three years ago. The field has moved a coming on board. Even funding agencies are long way since then. Personalised health has changing their approach: The National Institutes become more of a reality today,” says Steinmetz. of Health in the United States have made preci-

He defines personalised or precision health as a ©EMBL Photolab - Marietta Schupp sion medicine a major priority. systematic, proactive approach to medicine that The use of mobile devices is just one tiny part Conference co-organizer Lars Steinmetz: emphasises maintaining wellness as well as treat- in the mosaic of new methods needed to drive “Personalised health has become more of a ing disease. Through comprehensive data analy- the change. As Minor remarked in his talk, by reality today”. sis, personalised health will enable more targeted 2020 eighty per cent of the adult population will treatments and the prevention of disease before own a smartphone. The devices might be used to it arises. monitor people’s blood pressure, glucose levels Gathering genome sequence information double affiliation to other people,” says Steinmetz and heart rhythm and to alert the doctors when for a growing number of individuals is only who coordinates this transcontinental Alliance. risk factors start to show for a particular person. the beginning. Today there are several hundred He and his colleagues envision a partnership that “If today we can monitor billions of credit card actionable variants that can be obtained from enables high-risk, high-gain projects, strengthens transactions in real-time, surely we can monitor genome sequencing – depending on how action- links between Europe and the US and leverages physiological parameters too,” said Minor. “We able is defined. Even more important will be complementary strengths. “This alliance is a win- have not gotten there yet but it is coming.” So personal molecular profiling to analyse disease win situation for both partners,” he is convinced. even if the smartphone in your pocket will never and manage health – the collection of additional It will also open up new funding opportunities, entirely replace a doctor, it might in future do a information including epigenome, transcriptome, as funding bodies and private donors might be lot more than just connect to the internet – it may proteome, metabolome and microbiome data. interested in supporting research efforts that span one day provide a window into your health. The integration of these interdisciplinary datasets the Atlantic. is necessary to tackle the challenges in precision “This is a wonderful collaboration that has www.embl.de/training/events/2015/PEH15-01/ health. arisen from the faculty, from the scientists enjoy- http://med.stanford.edu/ A collaboration between Stanford University ing the synergies. I am eager to see it going to www.genomicsengland.co.uk/ School of Medicine and EMBL was launched at the next levels,” said Lloyd Minor, the Carl and the-100000-genomes-project/ the conference and is poised to help realize these Elizabeth Naumann Dean of Stanford University efforts. The Life Science Alliance will foster inter- School of Medicine, in his talk at the official kick- action between both institutions across several off ceremony on day four of the conference. domains enabling scientific cooperation, staff and Particularly in the area of genome biology, postdoc exchange, joint symposia and workshops, Stanford and EMBL complement each other mutual access to leading facilities and training. very well as Steinmetz explains. EMBL is a “I have had a laboratory between EMBL and leader in the integration of laboratory expertise Stanford for twelve years now and I want to bring with computational know-how. Its strength in the benefits that I experienced from having this basic sciences meshes very well with clinical

Only about 30 per cent of these homozygous individuals go on to get the actual disease. Two observations suggested this individual had active hemochromatosis. First, blood tests revealed that his iron levels were very high. Second, arthritis can be one early finding of this disease. Moreover, hemochromatosis can progress to a serious chronic disease as it can attack the pancreas (diabetes), the liver (fibrosis) and the heart (decompensation). Thus, his health coach advised him to go to a doctor. Hemachromatosis is actionable and can be managed by bringing down the blood iron levels by removing a unit of blood every month until normal iron levels are achieved. After these treatments, his arthritis disappeared and his hemochromatosis was under control. He is one of a number of examples we achieved in reversing disease transitions. ©Institute Seattle Biology, for Systems

What was the participants’ feedback? Most individuals felt that this was a really trans- Our genome is not our destiny forming experience because they understood that their genome is not their destiny. Indeed, many EMBO Associate Member LEROY HOOD is president of the Institute for learned that changes in lifestyle could control Systems Biology (ISB) in Seattle, United States, and senior editor of the consequences of many genetic defects. They realize with enough information that they could EMBO's open access journal Molecular Systems Biology. At the first joint take control of their own health. I feel that this EMBL | Stanford Personalised Health Conference he presented his vision is an important step in bringing down the costs for P4 Medicine – predictive, preventive, personalized, and participatory. In of healthcare. They also began to realize that the journey of scientific wellness is probably going to a keynote speech, he described the 100K Wellness Project he launched last be life-long journey and not just for a month or year as president of the Institute for Systems Biology. The study aims to a year. Indeed, as more and more data are accu- track the biometrics of 100,000 participants over 20 years. The pilot study mulated, new kinds of actionable possibilities are being uncovered, opening up new opportunities involving 108 participants was concluded in 2014. In an interview with for each individual to further optimize their own Thomas Lemberger, chief editor of Molecular Systems Biology, Hood talks wellness. Most people were so enthusiastic that about how he defines wellness and his objective to provide actionable the vast majority of them have gone on to the next stage of this programme. information to the participants of the study. The next stage is the creation of a consumer- facing scientific wellness company that utilizes the scientific wellness strategy described above. Why do you focus on wellness? aim of the study was to identify actionable possi- We easily raised about 40 million US dollars to In classic healthcare, physicians wait until the bilities that could improve their wellness or assist fund this company. In just six months we have patient exhibits visible symptoms of a disease. them avoiding disease. The study collected data recruited more 1000 people and now we have This however generally happens only long after at daily and three-month intervals. Each partici- a long waiting list. It is very likely that within the initial transition from a healthy state to disease. pant had their whole genome sequenced at the 18 months we will have 10,000 individuals with And after this long period following the intitial beginning and every three months provided dense and dynamic personalized data clouds – transition the disease often becomes irreversibly samples of blood, saliva, urine, and stool for clin- meaning that we will have more than hundred altered. I think that wellness is the fundamental ical parameters analyses, metabolite, proteomics times as much data as we have today available key to health in the future. The reason for this measurements and microbiome profiling. We for analysis. is really twofold. Firstly, one needs to optimize also used wearable devices to gather quantitative the wellness of the individual to maximize their longitudinal data on physical activity, pulse and Are there clear boundaries between wellness human potential – feeling well both mentally and quality of sleep. and disease? physically. Secondly, we need to be able to follow No, the boundaries are not clear. If you look at the wellness to disease progression to identify What did this pilot study reveal? definitions of wellness they are all psychiatric or the very earliest point of change. Analyzing this It turned out that every single one of the 108 psychologically-oriented definitions. What we critical earliest disease phase will allow one to individuals had multiple actionable possibilities found is that by identifying actionable possibili- develop diagnostic and therapeutic approaches during the course of the study. For example, we ties from each individual’s dense and dynamic that can revert back to wellness immediately. In a found that 53 of them were pre-diabetic and five data cloud, you can deal with wellness in a more sense, this is “preventive” medicine: We want to per cent of them actually had chronic diseases objective manner – specific for each individual. take all the common diseases, figure out what the without being aware of it. Moreover, in analysing individuals that transition earliest transitions are and develop approaches to One participant was a poster-child example of from wellness to greater wellness, we can begin revert them back to wellness immediately. having an unknown chronic disease. He displayed to identify blood biomarkers for wellness that a gradually increasing degree of arthritis that will provide a quantitative assessment of well- What is the Hundred Person Wellness Project? prevented him from hiking with his wife. His ness – eventually both physical and mental. Two years ago we invited 108 volunteers to be genome sequence revealed that he was homozy- intensely monitored for a ten-month-study. The gous for the genetic defect of hemochromatosis. Interview continues on the next page →

How did the participants’ physicians react to What will it take to bring the scientific wellness Facial features represent complex phenotypes the study? approach to clinics? and potentially are a rich source of systems-inte- A third of the physicians were absolutely enthu- We need to convince the payers (insurance grated information. What computer facial recog- siastic and wanted to learn all about it. A third companies) that the scientific wellness approach nition software can achieve these days is incred- were indifferent – they were too busy to think is really going to save healthcare dollars. I am ible. Leveraging this technology to explore how about it. And a third of them had concerns about confident that if we can develop ten thousand dynamical facial measurements relate to disease the project. I think for the latter group it was dense and dynamic data clouds we will have transition is going to be fascinating. mostly a defensive reaction to something they enough examples to begin to set up compelling We are also working on a protein chip to did not understand. A key task we have ahead of economic and social arguments for this approach. get 2500 organ-specific proteins: fifty proteins us is to educate physicians as to the benefits of In fact, we are beginning to approach health- from each of 50 different organs. From a drop of scientific wellness. care systems to convince them to become payers blood once a month these assays will allow you directly in order to benefit from savings that to follow wellness to disease transitions for all How does your approach fit with the role of the come from scientific wellness. of your major organ systems. Once you set such FDA? assay systems up they are infinitely stable. The FDA has a responsibility to prevent direct- Which technological developments are you There are two areas we consider really impor- to-consumer companies, such as Arivale, from particularly interested in for longitudinal tant in the future. One is the immune response, practicing medicine. Hence Arivale has been very personal phenotyping? which is involved in every disease and many careful to avoid any hint of practicing medicine. In wellness, one of the things you want to do is aspects of wellness. The other thing I want to do We have MD’s analyse the individual data and to measure complex traits that integrate many deep phenotyping on is the brain. I would like talk with the coaches about what are appropri- different types of physiological information. A to be able to map specific changes in different ate actionable possibilities. We obviously learn great example is heart rate variability: it beauti- regions of brain. Those are the areas of oppor- a great deal about individuals that we cannot fully integrates parasympaphetic and sympathetic tunity that I really see coming: Obtaining and communicate to them because this would be nervous system activity. A restricted heart rate measuring more complex phenotypes and going view as practicing medicine (e.g. pharmacog- variability is unhealthy and often reflects some deeply into systems that are really critical for enomics variants that provide insights about how type of disease. humans. The immune system is one of them and individuals react to common drugs). the brain another one.

it has given me access to the best scien- Nine tists in Europe, all of whom have been contemporary very supportive and receptive to idea artists exchange. Secondly, the programme has contributed to the exhibition specifically encouraged collaborations # Hashtag, between systems biology and basic Visions of biology groups, which has dramatically Epigenetics. enriched my research.” Here: X & O EpiGeneSys also includes an exten- by Paul L. sive training scheme: 850 young scien- Harrison and tists attended seven courses, ten work- Lia Giraud’s Education à la shops and two summer schools, as well danse (right) as four open calls for small research projects, all dedicated to building a bridge between epigenetics and systems biology. Additionally, the lab exchange programme has supported approx. 600 lysse Fiévé ia Giraud (PSL/EnsadLab/La Paillasse) ia Giraud

©U ©L days of training for junior researchers. A Science in Society programme sought to leave the confines of the ivory tower: The EpiGeneSys final meeting in Paris research of the network inspired nine contemporary artists, who contributed last May to the exhi- fter five-and-a-half years, the FP7 Network questions of epigenetics. The network’s interdis- bition #Hashtag, Visions of Epigenetics, which of Excellence EpiGeneSys (Moving ciplinary approach has demonstrated how syner- attracted several hundred people on the opening AEpigenetics Towards Systems Biology) gies between disciplines help to provide compre- night alone. will reach the end of its lifetime as an EC-funded hensive answers to current scientific challenges. It is clear that the network has to continue initiative at the end of March 2016. Led by EMBO So far, almost 360 papers have been published in one way or another. Coordinator Geneviève Council member Geneviève Almouzni, director of stemming from EpiGeneSys research. Almouzni sees the final meeting that took place the Research Centre at Institute Curie and coor- The network put a special focus on career from 11 – 13 February in Paris, as a new beginning dinated by the Centre National de la Recherche development with a programme for junior group for promoting scientific exchange, mentoring and Scientifique (CNRS), the network has outgrown leaders. The 20 young PIs selected through open training opportunities. The main objective is to its beginnings of 22 teams and now unites more calls have put their stamp on the activities of the take scientific interaction to an international level than 170 laboratories all across Europe from the network, and in turn benefitted from the oppor- beyond Europe. areas of epigenetics and systems biology. tunities offered. Suzana Hadjur, group leader at The focus of the EpiGeneSys research University College London, describes her experi- www.epigenesys.eu programme lies on using computational meth- ence: “The RISE1* programme has been instru- * RISE1: Research Integrating Epigenetics and Systems Biology ods and mathematical modelling to address key mental in the success of my young group. First,

residues. With this information at hand, both From Parkinson’s Disease Komander and Walden, together with collaborators and alongside the group of Kalle Gehring at to ubiquitin Montreal’s McGill University, could now struc- turally and biochemically define how binding Mechanistic studies on a few curious proteins associated with familial of phosphorylated ubiquitin released the Ubl Parkinson’s disease have led researchers in the EMBO community on a domain from Parkin’s ubiquitin ligase module, and how subsequent phosphorylation of the Ubl journey to cast surprising new light on the universal cellular ubiquitin domain further facilitated Parkin release from modification system. auto-inhibition.3,4,5,6 Says Walden, now at the MRC Protein Phosphorylation and Ubiquitylation eurodegenerative disorders, includ- suggesting for the first time how they affect Unit in Dundee, “It was immensely gratifying to ing Alzheimer’s (AD) and Parkinson’s Parkin function in cells.1 finally see all Parkin domains at atomic resolu- Ndisease (PD), have become a major Further understanding of Parkin function tion, providing a molecular explanation of our burden especially in Western societies. They and the effect of PD mutations required insights puzzling initial observations and interpretations.” usually unfold gradually due to sporadic muta- on Parkin’s molecular structure, but despite his While there is still a long way to go towards tions as people age, and consequently the molec- curiosity, structural biologist David Komander at fully understanding the molecular pathology of ular causes of these pathologies have been diffi- the MRC Laboratory of Molecular Biology (LMB) Parkinson’s Disease, the exciting new findings cult to understand and reconcile into unifying in Cambridge initially shied away from such a about Parkin auto-regulation may in time enable schemes. However, less frequent familial forms, project. “Since I knew that several groups had the design of therapeutic compounds that trigger Parkin activation despite PINK1 or Parkin mutation, and hence rescue disease phenotypes. However, they have also revealed intriguing insights into the universal cellular regulatory mechanism of ubiquitin conjugation, whose seminal discovery had been honored with the 2004 Nobel Prize in Chemistry to EMBO Members Avram Hershko and Aaron Ciechanover. Ubiquitin consists of only

©CRUK Institute London Research ©MRC Laboratory of Molecular Biology 76 amino acids and was generally considered an Helen Walden David Komander with his student Tobias Wauer (on the left) inert post-translational modifier, but as the Komander lab could show often developing already early in life, have been been trying to achieve this for a while, I told my in additional work, its own post-translational causally linked to inherited mutations in specif- student to rather focus on related proteins”, says modification by PINK1 phosphorylation not only ic genes, whose study may therefore shed light Komander, also an EMBO Young Investigator at affects enzymatic conjugation and deconjugation onto underlying disease mechanisms. This is why the time and now EMBO Member. However, his of ubiquitin, but can also alter its three-dimen- EMBO Young Investigator Helen Walden, when student Tobias Wauer was undeterred and while sional conformation.7 “That the well-known and starting her own lab at CRUK’s London Research proceeding with his main project, continued intensely studied ubiquitin molecule undergoes Institute, focused on a protein called Parkin. with attempts to crystallize Parkin constructs such conformational change is mind-boggling, Mutations in the parkin gene are among the most on the side. “Only when he had his first promis- and suggests there may be yet-unidentified bind- frequent causes of hereditary early-onset PD, but ing results did he admit this to me”, Komander ing partners for the new conformation”, says it was not clear how all of these mutations affect recounts, “and after that everything went very Komander. So the journey from disease pathology the Parkin protein, a ubiquitin ligase capable of fast. Because of rumors about competing studies, to basic cell biology and back is sure to continue, linking chains of ubiquitin to itself and to other we submitted a manuscript to The EMBO Journal, with more exciting findings to come. substrate proteins. With an interest in ubiqui- where we knew that we had ‘scooping protection’ tination mechanisms originating from her post- while under consideration.” Their crystal struc- REFERENCES doctoral research, Helen decided to characterize ture showed Parkin’s ubiquitin ligase domain in 1. Chaugule et al. (2011) The EMBO Journal 30(14): wild-type and mutated Parkin proteins in vitro. the auto-inhibited state, and together with three 2853 – 2867 Looking at full-length Parkin, a multi-domain related structural studies appearing at the same 2. Wauer & Komander (2013) EMBO J 32(15): 2099 – 2112 3. Wauer et al. (2015) Nature 524(7565): 370 – 374 protein, she surprisingly discovered that it is not time, helped to understand several more disease 4. Kumar et al. (2015) The EMBO Journal 34(20): 2506 – 2521 2 constitutively active as commonly assumed, but mutations in the protein. 5. Sauvé et al. (2015) The EMBO Journal 34(20): 2492 – 2505 auto-inhibited by one of its accessory domains. But how was Parkin activated? Helpful clues 6. Kazlauskaite et al. (2015) EMBO reports 16(8): 939 – 954 Several disease mutations cluster in this ubiqui- came from the study of another protein, PINK1, 7. Wauer et al. (2015) The EMBO Journal 34(3): 307 – 325 tin-like (Ubl) domain, so-called for its sequence whose gene is also the target of hereditary PD resemblance to ubiquitin itself. Strikingly, when mutations. PINK1 is a protein kinase involved By Hartmut Vodermaier introduced into the recombinant protein, these in Parkin activation, and strikingly, it turned out Senior Editor, The EMBO Journal mutations disrupted the intramolecular inter- to directly phosphorylate both ubiquitin and the actions and resulted in loss of auto-regulation, Parkin ubiquitin-like domain on corresponding

EMBO INSTALLATION GRANTEE 2015 scientists with excellent international backgrounds joined my team right from the start, which made the hard and stressful work of establishing the Sebastian lab a great team-building experience. Changing directions Originally, I am a trained cell biologist who turned Glatt into a structural biologist and protein biochemist during my time at EMBL 2015 EMBO Installation Grantee in Heidelberg. I am fascinated by the atomic details that x-ray crystallogra- Malopolska Centre of phy and electron microscopy provide these days, but for me the translation Biotechnology (MCB), of structural information into functional knowledge is still the most exciting Jagiellonian University, Krakow, moment in science. I would like to specifically acknowledge my former boss, Poland Christoph W. Mueller, who has strongly supported and mentored me over the last few years. ©Katarzyna Tarnawska, University of Krakow ©Katarzyna University Tarnawska,

What are you working on at the moment? My group is interested in the What made you go to Poland? My position as a Max Planck Research Group detailed structural and functional characterization of tRNA modification Leader outside of Germany is quite unique and offers lots of opportunities enzymes and other macromolecular complexes involved in the control of and responsibilities for a junior group leader. I was very interested in the protein synthesis using x-ray crystallography, electron microscopy, biochem- opportunity to act as a link between a new research institute in Poland and istry and cell biology. The resulting tRNA modifications act as gatekeep- an established research institution abroad. And Krakow is a truly beautiful ers for cellular proteomes. Alterations of these modification pathways in city and in many aspects reminds me of Vienna, my hometown. humans are associated with the onset of neurodegenerative diseases, specific cancer types, and also affect intellectual capabilities. What were your first five months like at the MCB? The team around Kazimierz Strzałka (MCB Director) was very helpful during the installation phase and after merely a few weeks we were able to conduct the first experiments. In addition, the EMBO Installation Grant allows me to carry out additional research ideas. I have also been very lucky that several young

EMBO ADVANCED FELLOW 2014 Furthermore, the funding gave me freedom to write a successful grant application and to start preliminary experiments for the next stage of research. In my opinion, it is impossible to achieve all this with only two years of David postdoctoral funding.

Schwefel In May, you will establish your own laboratory at the Charité. How excited 2014 EMBO Advanced Fellow are you about moving to Berlin? I am very excited to move on to my new The Francis Crick Institute, DFG-funded position in Berlin, and about the chance to pursue my own line London, United Kingdom of research. It will be hard work, but now we also have more hands to do it. I am very grateful for this opportunity.

What does it mean to you to be part of the EMBO network? The EMBO ©private network is the cornerstone of my scientific career. The Long Term Fellowship provided me with the means to gain international research expe- What fascinates you about structural biology? As a structural biologist, I rience, which I value very much, and the Advanced Fellowship allowed me am fascinated by the possibility of obtaining direct insights into the inner to continue and extend the work. Moreover, The EMBO Meetings are always workings of cells, and the possibility of generating testable models of cellu- a good opportunity to learn something new and to meet old and new friends. lar processes. Specifically, I am interested in how viruses hijack the cellular Especially, I would like to recommend the EMBO Laboratory Management protein degradation machinery to get rid of antiviral host factors. Here, you Courses, which introduce new lines of thinking into the daily lab and office can learn a lot about viral replication itself, and what mechanisms the host routine. uses to fight virus infection. In future, I would also like to extend these studies to learn how specificity is generally achieved in protein degradation and What is your vision for your research & career? I would like to continue to how the degradation machinery could be modified. pursue solid and innovative basic research in order to add to the understanding of my specific area of work and life sciences in general. How did the EMBO Advanced Fellowship help your career? The EMBO Advanced Fellowship was very important to bridge the gap between the end of my first two postdoc years and the present time. We already had important results, but the additional funding allowed us to complete our work.

EMBO YOUNG INVESTIGATOR 2015 lab by collaborating with students and postdocs who needed help solving crystal structures of CRISPR-associated proteins. Thanks to this, I gradually Martin became more interested in the CRISPR systems and was looking to work on my own standalone project. I ended up picking Cas9 and the rest, as one Jinek might say, is history. 2015 EMBO Young Investigator Is the hype around CRISPR helpful for your own research agenda? The University of Zurich, Switzerland CRISPR revolution has certainly helped to get exposure for my new lab in Zurich and attract funding for my research. Very early on, we managed to determine crystal structures of the Cas9 genome editor and its complexes, which helped to prove my scientific independence. CRISPR-Cas genome editing has attracted a lot of attention from the media. While all this public- ©Jos of Zurich Schmid/University ity has generally been very good for us, it also meant that I have to dedicate part of my time to working with journalists and to public outreach, which What do you like about being a scientist? What I like most is having the takes time away from research. freedom to pursue my natural curiosity and study the molecular basis of life. Doing an experiment that gives an interesting result and realizing that What is your current research focus? My lab is focused on two general you might be the first person in the world to discover something new is a themes: RNA biology and genome editing. We continue studying the molec- great feeling. Having had my own research group for three years now, I also ular mechanisms of CRISPR-Cas systems, both to shed light on the basic discovered that I really like working with people. I still think that running biology of these systems and to contribute towards further development of an academic research lab the best job in the world. It can be stressful some- genome editing technologies. We actively collaborate with labs that develop times, but it’s a lot of fun too. applications or apply genome editing to study interesting biological problems. My other projects focus on protein-RNA interactions and complexes What is it that you do not like? I do not like it when science gets political involved in eukaryotic RNA metabolism. In our work, we combine struc- and when personal clashes get in the way of doing good science. tural biology with biochemical approaches to obtain insights at the atomic level. What was your career like before and after CRISPR? I am a chemist by training and I did my PhD in structural biology, specifically X-ray crystal- Which part of the Young Investigator package is particularly interesting to lography. Due to my interest in RNA biology, I chose to go to Berkeley you? The annual PhD student course is a great benefit and will help with to Jennifer Doudna’s lab to study RNA-mediated gene regulation for my training my students in scientific writing and presentation skills. I also like postdoc. There, I initially worked on projects (some successful and some the idea of the sectoral special topic meetings and I am looking forward to not) focusing on macromolecular complexes that mediate microRNA-guided participating in them. RNA silencing. I got involved in the CRISPR-focused effort in the Doudna

EMBO ADVANCED FELLOW 2014 New position The Institute of Molecular Biology (IMB) at Academia Sinica is a leading research institute in Taiwan. I am very excited to work as a Suewei Lin research fellow here and looking forward to making some interesting discoveries. I also enjoy working in my home country, close to my family. 2014 EMBO Advanced Fellow Institute of Molecular Biology, What does it mean to you to be part of the EMBO network? It means I am Academia Sinica, Taiwan connected to many brilliant scientists around the world! Through the EMBO network I also receive updates on lots of great meetings and courses, which is very useful for a young scientist like me.

What is your research area? I study the molecular and neural mechanisms that underlie thirst-driven water seeking behavior in the fruit fly Drosophila. ©Academia Sinica Thirst is a physiological state that influences how a fly values water vapor and learned olfactory cues previously associated with water. When exploit- Selection as EMBO Advanced Fellow Last year I was fortunate to be award- ing the neural circuit of thirst in Drosophila, powerful genetic techniques ed an EMBO Advanced Fellowship. It gave me an edge in the job market and and the relative simplicity of the brain allow us to manipulate neural circuits helped me land my current position at the Institute of Molecular Biology at with fine temporal precision at single-cell resolution. By doing this I hope Academia Sinica, Taiwan. My initial EMBO long-term fellowship, received to gain a better understanding of how the brain integrates multiple pieces of in 2013, allowed me to continue my postdoctoral work in the fantastic lab information such as sensory cues, internal states and memory, to select an of Scott Waddell at the Centre for Neural Circuits and Behaviour at the appropriate course of action. University of Oxford, where I laid the foundation for my current research.

n a paper published in September 2015, path to reach a therapeutic solution. Domingos is Domingos and her lab showed that sympa- working out the fundamental biology underlying New hopes Ithetic neurons directly innervate adipocytes. a new generation of anti-obesity compounds that These sympathetic neurons are the peripheral she coined as targeted sympathomimetic drugs for treating effectors of leptin action in the brain, to mediate (TSDs). fat break-down. The newly discovered neurons Obesity is a worldwide epidemic with unmet in fat close the neuroendocrine loop of leptin medical need. Most anti-obesity therapies that obesity action in the brain, to promote lipolysis, and have been approved by the regulatory agencies keep fat mass in a very narrow window of vari- were later withdrawn from the market due to Recent results from the young ation. Domingos’ team tested the function of the severe side effects. For instance, reverse agonists laboratory of ANA DOMINGOS, sympathetic neurons using optogenetics. They of the cannabinoid receptor-1 (CB1) are potent an EMBO Installation Grantee found out that local activation of the sympathetic appetite suppressants. However, in 2007 and neuron-adipose junction is sufficient to promote shortly after market introduction, several reports at the Gulbenkian Institute lipolysis and fat mass reduction. According to the of deep depression and suicidal thoughts made of Science, Portugal, put lead author of the study: “This result provides the US Food and Drug Administration (FDA) vote forward the idea that a new hopes for treating central leptin resistance, a against its approval as an anti-obesity therapy. condition in which the brains of obese people are The side effects stem from unspecific action in sympathomimetic action insensitive to leptin.” the brain, which seems to be a recurring concern away from the brain could be The possibility of achieving fat mass reduc- in anti-obesity medication. Not surprisingly, some the way to treat obesity. Her tion by targeting these peripheral neurons, with- of the most efficient anti-obesity compounds sit out interfering with the brain, is now subject of in the broad class of sympathomimetic drugs, research results triggered a many debates. Specifically, why target the central such as amphetamines that suppress food intake. debate among neuroscientists nervous system if the track record of brain target- However, the sympathomimetic nature of this worldwide on how to address ing anti-obesity compounds has been deceptive? class of drugs has mostly been regarded as a Moreover, considering the difficulties of getting side effect, and not at the core of the anti-obesity obesity therapeutically. drugs across the blood-brain barrier, targeting the mechanism. brain may be neither the shortest, nor the safest

500 scientists and more than 1,300 students. The institute works closely with local government to shape the regional innovation strategy. As the first scientific centre in the Czech Republic, it integrates Research & Development in the fields of life sciences, advanced materials and technologies. After an initial exodus of their young scientists, the Czech Republic – among other Eastern European countries – is seeing a return of its talents back home. Four life scientists have received an EMBO Installation Grant to set up their laboratories at CEITEC: Lukáš Trantírek, Peter Lukavský, Pavel Plevka and Karel R˘íha. CEITEC also hosts international conferences ©CEITEC and workshops including EMBO funded events such as the Practical Course Analysis of small Succeeding non-coding RNAs: per aspera ad astra held in July 2015, and the EMBO Conference Signalling in Plant Development held last September. in science in „Our most important task is to focus on the The Central European Institute of Technology quality of science and to support the best scien- Central Europe (CEITEC) in Brno, Czech Republic, is addressing tists to achieve success. As a unique institute in these challenges by bringing in best practices that Central Europe, CEITEC has a lot to offer. We are The Central European Institute exist in other parts of the world. The institute was looking for ways to engage more with interested of Technology is setting an established by Masaryk University and approved partners, which can help CEITEC become an inte- example for the entire region. by the European Commission in 2011. The under- gral part of the international scientific commu- lying premise for the formation of CEITEC was to nity, “ states CEITEC Executive Director Markus improve the research potential of the organiza- Dettenhofer. entral and Eastern Europe still face many tion and the region in general, but also to spark challenges in the way science is being transformation in the way research is done in the www.ceitec.eu Cperformed – although more than a quar- Czech Republic, to support entrepreneurship and ter of a century have passed since the fall of the innovative business models. iron curtain. Changes in the form of bureaucracy, Five years on, CEITEC has gained an immense infrastructure and general practices have not influence in the entire region. The new labora- been as rapid as within the private sector. tories, completed in 2015, offer jobs for nearly

A new programme “International Research Boost for basic and applied science Agendas” supports the creation of specialised scientific units in Poland applying global best in Poland practice with regard to research programmes and topics, Human Resources policy, management of The Foundation for Polish Science (FNP), headed by EMBO Member Research & Development and commercialisation MACIEJ Z˙YLICZ, is launching a new programme for financing innovative of its results. The funding amounting to the total of 615 research in Poland. Funding will be available for experienced researchers million PLN until 2023 (roughly 154 million as well as young postdoctoral students seeking support for establishing Euros) will cover more than 350 grants and their first research group. A special fund is reserved for people with support more than 2,100 researchers. Recruitment rounds will take place twice a year until 2019. experience in implementing research results for the development of

technologies, processes or innovative projects in cooperation with www.fnp.org.pl commercial partners. www.fnp.org.pl/en/oferta/ international-research-agendas-ira/

he Foundation will also make it easier for postdoctoral researchers to return to Tscience after parental leave or after working in a non-scientific area. Postdoctoral fellowships will be offered to researchers wishing to return to Poland or to come to Poland from abroad. “The funding programmes are pursuing two goals,” said Maciej Z˙ylicz. “First, to invest in people. We want the well-equipped laboratories that have been built in recent years in Poland to be The Foundation filled with outstanding researchers from Poland for Polish Science, and abroad, pursuing research to meet contempo- founded in 1991, rary challenges. Second, to bring science and the is the largest source economy closer together. We want members of of science funding the scientific and business communities to enter in Poland outside into an effective dialogue so that research results the state budget

are not filed away, but implemented and used by ©Foundation Science for Polish entrepreneurs.”

hrough the centre, King’s College London aims to drive collaboration between scien- Ttists and clinicians to translate the potential of stem cells into clinical reality for patients. The goal of the centre is to understand how stem cells interact with their local environment. Its 54 (and counting) investigators work on different types of stem cells but have a common interest in how interactions with the environment affect cell behaviour. “By bringing different types of expertise to bear in a collaborative environment I think we can do some exciting work. We are very well placed being in one great teaching hospital and affili- ated to other hospitals. We can reach out to the Fiona Watt with guests at clinicians, offer collaborative resources and learn the launching ceremony from them,” said centre director Fiona Watt, who ©Centre Medicine London for Stem Cells and Regenerative has been announced as this year’s FEBS | EMBO Women in Science Awardee (see also article on New hub for stem cell research page 5). The institute is supported by major funders of EMBO Member Fiona Watt is heading the new Centre for Stem Cells UK biomedical research including the Wellcome and Regenerative Medicine, which was launched at Guy’s Hospital Trust and the Medical Research Council. It has recently been refurbished at a cost of more than in December 2015. The centre brings together stem cell research eight million British Pounds. The 150 guests who currently taking place across King’s College London and its partner gathered to celebrate its launch last December enjoyed splendid views from the centre, which is the NHS Trust. situated on the 28th floor of Guy’s Hospital Tower Wing in central London.

members of the institute and their groups partici-

©IFOM pate in the programme. Students also attend a science communica- Science: tion course to learn how to communicate science topics to different audiences. They elaborate an experience scientific posters and write popular science arti- cles to describe to a lay public their results and to share their experience in science. Science communication products are disseminated during a final Who says students prefer to celebrative event, the Poster Day, where students spend their holidays at the discuss their results in front of scientists, but also other students, families and teachers. seaside, relaxing and enjoying Over the last few years, approximately 200 the sun? For some of them students attended IFOM summer school: 62% of working for two intense weeks them enrolled in bio-medical Universities, while 28% of them enrolled in other scientific faculties. in an international basic When asked whether their experience in IFOM research laboratory in close was useful in helping to choose the course of contact with scientists and study, 91% answered positively. Indeed, before attending the summer school most of them current technologies is a great declared an interest in science, but were still way to spend summer. undecided about their future. Initiatives such as the IFOM summer school are an effective way to inspire young generations of scientists-to-be. They also increase the his is the opportunity that YouScientist, awareness among scientists of the importance of the science and society program of the outreach activities and of sharing their passion TFIRC Institute of Molecular Oncology for research. (IFOM) based in Milan, Italy, offers every year to ten talented Italian high schools students Assunta Croce through its summer school “Lo studente ricerca- Head of the YouScientist program tore”. Every year, hundreds of students in their ([email protected]) 4th grade are selected based on an online test to www.ifom.eu/en/science-society Student with assess their scientific literacy and their academic a scientist at a performance. The best ten candidates, with the summer school direct supervision of a tutor, begin a full immer- at IFOM sion experience into the scientific life of the institute: they perform experiments at the bench, but also participate in lab meetings and lectures, discussing science with scientists. All the EMBO

BOOK REVIEW A science thriller fter working for 25 years as an active who served as editor in chief of The EMBO Ascientist, EMBO Member Pernille Rørth Journal for five years. “I wanted to tell a story has written a novel about life in science – a that would make the world of lab science come fascinating portrait about the world of top-level alive for non-scientists, while keeping it real for science. The book entitled Raw Data is focused scientists. Scientific misconduct is placed at the on two young scientists at a critical stage of dramatic centre. It has enormous consequences, their careers. Chloe and Karen work in a top- yet is often somehow banal. It also cuts to the tier research institute in the United States and heart of what science is.” are both about to set up their own independent laboratories. This stressful time is a fertile Raw Data: A Novel on Life in Science ground for frustration, jealousy and fear of Pernille Rørth being scooped, but also for exciting discoveries Springer and personal recognition. An investigation of February 2016 potential misconduct is part of the plot. ISBN-10: 3319239724 “The story is pure fiction and not a fiction- alized version or a real case,” assures Rørth,

THE EMBO EMBO JOURNAL Molecular Medicine

Pluripotent MetaTAD with coherent Accumulation stem cells expression change Young of A in the β 6 extracellular 3 Stress or SASP replication matrix 2 Senescent 5 4 Differentiation mTOR ROS + + 1 5 PGC-1β 3 2 RESEARCH ARTICLE + + + + 4 6 Mitochondria drive senescence 1 + + + + Post-mitotic Cell senescence is an important RESEARCH ARTICLE neurons MetaTAD re- arrangement tumor suppressor mechanism and RESEARCH ARTICLE driver of ageing. Both functions Role of PITRM1 in RESEARCH ARTICLE are dependent on the development neurodegeneration Dominant-negative toxins to of senescent-associated changes combat Staphylococcus aureus Dynamic changes in chromatin Two siblings of a consanguineous in gene expression and protein pathogenesis contact hierarchies family with a peculiar and slowly secretion. However, the exact progressive neurodegenerative Mammalian chromosomes fold mechanisms regulating these S. aureus is a human pathogen disorder of unknown origin were into arrays of megabase-sized phenotypes remain poorly that relies on the subversion of investigated to establish the cause. topologically associating domains understood. Here, we show the host phagocytes to support its We found a homozygous, disease- (TADs), which are arranged into critical role of mitochondria in pathogenic lifestyle. S. aureus segregating missense mutation compartments spanning multiple cellular senescence. In multiple strains can produce up to five beta- in the PITRM1 gene in both megabases of genomic DNA. TADs models of senescence, absence barrel, bi-component, pore-forming siblings. The pathogenic role of the have internal substructures that are of mitochondria reduced a leukocidins that target and kill mutation, which causes PITRM1 often cell type specific, but their spectrum of senescence effectors host phagocytes. Thus, preventing instability, was validated by in higher-order organization remains and phenotypes while preserving immune cell killing by these toxins vitro assays, characterisation of elusive. Here, we investigate TAD ATP production via enhanced is likely to boost host immunity. mutant fibroblasts from patients, higher-order interactions with Hi-C glycolysis. Transcriptome analysis Here, we describe the identification in PITRM1 knocked-down human through neuronal differentiation revealed that a vast number of of glycine-rich motifs within fibroblasts and in a mutant yeast and show that they form a senescent-associated changes the membrane penetrating stem model. A hemizygous PITRM1 hierarchy of domains-within- are dependent on mitochondria, domains of the leukocidin subunits knockout mouse displayed reduced domains (metaTADs) extending particularly the pro-inflammatory that are critical for killing primary amounts of PITRM1 and slowly across genomic scales up to the phenotype. The ATM, Akt and human neutrophils. Remarkably, progressive neurodegeneration, range of entire chromosomes. mTORC1 phosphorylation cascade leukocidins lacking these glycine- characterised by accumulation of TAD interactions are well integrates signals from the rich motifs exhibit dominant- amyloid beta (Aβ) in the brain. captured by tree-like, hierarchical DNA damage response towards negative inhibitory effects toward In conclusion, we have identified structures irrespective of cell PGC-1β-dependent mitochondrial their wild-type toxin counterparts a clinically peculiar human type. metaTAD tree structures biogenesis, contributing to a as well as other leukocidins. neurodegenerative disorder caused correlate with genetic, epigenomic ROS-mediated activation of the Biochemical and cellular assays by a pathogenic, homozygous and expression features, and DDR and cell-cycle arrest. Finally, revealed that these dominant- mutation in PITRM1, a gene structural tree rearrangements we demonstrate that reduction negative toxins work by forming encoding an oligopeptidase of the during differentiation are linked of mitochondrial content in vivo mixed complexes that are impaired mitochondrial inner compartment. to transcriptional state changes. prevents senescence in the ageing in pore formation. The dominant- The neuropathology of a Pitrm1 Using polymer modelling, we mouse liver. Our results suggest negative leukocidins inhibited S. /+ mouse provides genetic demonstrate that hierarchical that mitochondria are a candidate aureus cytotoxicity towards primary evidence that Aβ is present within folding promotes efficient target to reduce the deleterious human neutrophils, protected mitochondria, and demonstrates chromatin packaging without impact of senescence in ageing mice from lethal challenge by a link between impaired PITRM1 the loss of contact specificity, tissues. wild-type leukocidin, and reduced activity and Aβ amyloidotic bacterial burden in a murine model highlighting a role far beyond the Mitochondria are required for pro-ageing neurodegeneration in mammals. simple need for packing efficiency. features of the senescent phenotype of bloodstream infection. Thus, Clara Correia-Melo, Francisco DM Defective PITRM1 mitochondrial we describe the first example Hierarchical folding and reorganization Marques, Rhys Anderson, Graeme Hewitt, peptidase is associated with Aβ of staphylococcal bi-component of chromosomes are linked to Rachael Hewitt, John Cole, Bernadette amyloidotic neurodegeneration transcriptional changes in cellular M Carroll, Satomi Miwa, Jodie Birch, Dario Brunetti, Janniche Torsvik, Cristina dominant-negative toxins and their differentiation Alina Merz, Michael D Rushton, Michelle Dallabona, Pedro Teixeira, Pawel potential as novel therapeutics to James Fraser, Carmelo Ferrai, Andrea M Charles, Diana Jurk, Stephen WG Tait, Sztromwasser, Erika Fernandez-Vizarra, combat S. aureus infection. Chiariello, Markus Schueler, Tiago Rito, Rafal Czapiewski, Laura Greaves, Glyn Raffaele Cerutti, Aurelio Reyes, Carmela Giovanni Laudanno, Mariano Barbieri, Nelson, Mohammad Bohlooly-Y, Sergio Preziuso, Giulia D'Amati, Enrico Baruffini, Exploiting dominant-negative toxins Benjamin L Moore, Dorothee CA Kraemer, Rodriguez-Cuenca, Antonio Vidal-Puig, Paola Goffrini, Carlo Viscomi, Ileana to combat Staphylococcus aureus Stuart Aitken, Sheila Q Xie, Kelly J Morris, Derek Mann, Gabriele Saretzki, Giovanni Ferrero, Helge Boman, Wenche Telstad, pathogenesis Masayoshi Itoh, Hideya Kawaji, Ines Jaeger, Quarato, Douglas R Green, Peter D Adams, Stefan Johansson, Elzbieta Glaser, Per M Tamara Reyes-Robles, Ashira Lubkin, Yoshihide Hayashizaki, Piero Carninci, Thomas von Zglinicki, Viktor I Korolchuk, Knappskog, Massimo Zeviani, Laurence A Francis Alonzo III, D. Borden Lacy, and Alistair RR Forrest, , Colin A Semple, Josée João F Passos Bindoff Victor J. Torres Dostie, Ana Pombo, Mario Nicodemi Read the paper: Read the paper: Read the paper: Read the paper: http://emboj.embopress.org/search/10.1525 http://embomolmed.embopress.org/content/ http://embor.embopress.org/content/ http://msb.embopress.org/ 2%252Fembj.201592862 early/2015/12/23/emmm.201505894 early/2016/02/08/embr.201540994 content/11/12/852

Practical Courses High throughput microscopy for Conferences Translational research in cancer cell systems biology metabolism Advanced optical microscopy DE-Heidelberg, 17 – 23 October 2016 Visualizing biological data (VIZBI ES-Bilbao, 4 – 6 October 2016 UK-Plymouth, 6 – 16 April 2016 2016) Solution scattering from biological DE-Heidelberg, 9 – 11 March 2016 Cilia 2016 Characterization of post- macromolecules NL-Amsterdam, 4 – 7 October 2016 translational modifications DE-Hamburg, 17 – 24 October 2016 Telomeres, telomerase and disease DK-Odense, 7 – 13 April 2016 BE-Liege, 26 April – 1 May 2016 Experimental approaches to Biomolecular interaction analysis evolution and ecology using yeast Single cell gene expression analysis 2016: From molecules to cells Imaging the brain and other model systems DE-Heidelberg, 11 – 16 April 2016 PT-Porto, 7 – 11 November 2016 PL-Warsaw, 18 – 21 May 2016 DE-Heidelberg, 19 – 22 October 2016

In vivo plant imaging Cellular signalling and cancer therapy Structure and function of the DE-Heidelberg, 24 April – 1 May 2016 HR-Cavtat, 27 – 31 May 2016 endoplasmic reticulum Workshops ES-Girona, 23 – 27 October 2016 Bioinformatics and genome analyses Gene transcription in yeast: From TR-Izmir, 2 – 14 May 2016 Multiple functions of piRNAs and chromatin to RNA and back From functional genomics to systems PIWI proteins ES-Sant Feliu de Guixols, 11 – 16 June biology Computational molecular evolution FR-Montpellier, 6 – 9 April 2016 2016 DE-Heidelberg, 12 – 15 November 2016 GR-Heraklion, 8 – 19 May 2016 Neural control of metabolism and The biochemistry and chemistry of Structural characterization of eating behaviour biocatalysis: From understanding to macromolecular complexes PT-Cascais, 5 – 7 May 2016 design EMBO | FEBS Lecture FR-Grenoble, 21 – 27 May 2016 Courses Molecular biology of mitochondrial FI-Oulu, 12 – 15 June 2016 Non-neuronal optogenetics: From gene expression Problems of listeriosis (ISOPOL XIX) Chromatin and the environment design to application in cell signalling SE-Bro, 23 – 26 May 2016 FR-Paris, 14 – 17 June 2016 GR-Spetses, 8 – 14 August 2016 and tissue morphogenesis DE-Heidelberg, 29 May – 4 June 2016 Mechanisms of neuronal remodelling Molecular and developmental biology The new microbiology DE-Seeon, 5 – 9 June 2016 of Drosophila GR-Spetses, 24 August – 1 September 2016 Computational analysis of protein – GR-Kolymbari, 19 – 25 June 2016 protein interactions: Sequences, RNA structure meets function SE-Stockholm, 12 – 15 June 2016 networks and diseases Ribosome structure and function EMBO | EMBL Symposia HU-Budapest, 30 May – 4 June 2016 Dendritic anatomy, molecules and 2016 FR-Strasbourg, 6 – 10 July 2016 Tumour microenvironment and Fluorescence microscopy methods to function GR-Heraklion, 18 – 21 June 2016 signalling study protein – protein interactions in Viruses of microbes 2016 DE-Heidelberg, 3 – 6 April 2016 living cells Membrane fusion in health and UK-Liverpool, 18 – 22 July 2016 FR-Rennes, 6 – 11 June 2016 New model systems for linking disease The nitrogen nutrition of plants: FR-Paris, 20 – 24 June 2016 evolution and ecology Regulatory small and long ncRNAs: Nitrogen 2016 DE-Heidelberg, 8 – 11 May 2016 Durat et lucet New model systems for early land FR-Montpellier, 22 – 26 August 2016 IT-Trento, 11 – 17 June 2016 Microtubules: From atoms to plant evolution Chemical biology 2016 AT-Vienna, 22 – 24 June 2016 complex systems Advanced methods of electron DE-Heidelberg, 31 August – 3 September DE-Heidelberg, 29 May – 1 June 2016 microscopy in cell biology Chromosome segregation and 2016 CZ-České Budějovice, 14 – 24 June 2016 Innate immunity in host – pathogen aneuploidy Lymphocyte antigen receptor IE-Galway, 25 – 29 June 2016 interactions Computational biology: Genomes to signalling DE-Heidelberg, 26 – 29 June 2016 systems AIDS-related mycoses IT-Pontignano, 3 – 7 September 2016 DE-Heidelberg, 19 – 23 June 2016 ZA-Cape Town, 13 – 15 July 2016 Actin in action: From molecules to Wnt meeting 2016 cellular functions 3D developmental imaging Advanced proteomics CZ-Brno, 14 – 17 September 2016 DE-Heidelberg, 7 – 10 September 2016 PT-Oeiras, 1 – 9 July 2016 IT-Varna, 31 July – 6 August 2016 The molecular and cellular basis of The complex life of mRNA Integrative modelling of biomolecular Molecular mechanisms of ageing and regeneration and tissue repair DE-Heidelberg, 5 – 8 October 2016 interactions regeneration: From pluripotency to IT-Laura, 17 – 21 September 2016 ES-Barcelona, 4 – 9 July 2016 Organoids: Modelling organ senescence Tuberculosis 2016: Interdisciplinary GR-Spetses, 16 – 24 August 2016 development and disease in 3D Correlative light electron microscopy research on tuberculosis and culture UK-Bristol, 10 – 15 July 2016 Integrating genomics and biophysics pathogenic mycobacteria DE-Heidelberg, 12 – 15 October 2016 FR-Paris, 19 – 23 September 2016 Multidimensional NMR in structural to comprehend functional genetic biology variation Retinal proteins DE-Joachimsthal, 10 – 15 July 2016 TR-Istanbul, 26 – 28 August 2016 DE-Potsdam, 2 – 7 October 2016 Global Exchange Lecture Courses Light sheet microscopy Actualizations in membrane trafficking in health and disease DE-Dresden, 15 – 26 August 2016 Structural and biophysical methods CL-La Serena, 4 – 9 September 2016 for biological macromolecules in Cryo-electron microscopy and 3D solution image processing Bacterial cell division: Orchestrating ORGANIZERS: KR-Suwon, 19 – 26 June 2016 DE-Heidelberg, 28 August – 5 September the ring cycle CZ-Prague, 14 – 17 September 2016 APPLY NOW FOR: 2016 Small brains, big ideas CL-Las Cruces, 10 – 19 November 2016 Analysis of high-throughput Cell size regulation 2017 funding for courses, work- sequencing data DE-Joachimsthal, 14 – 18 September shops and conferences by 2016 UK-Cambridge, 5 – 10 September 2016 1 March and 1 August 2016 Other EMBO events Protein expression, purification, and Organelle contact sites: Intracellular characterization (PEPC10) communication and role in disease Keynote lectures given by EMBO EMBO Laboratory Management DE-Hamburg, 12 – 20 September 2016 IT-Domus de Maria, 15 – 18 September members at major international Courses 2016 scientific meetings in 2017 by DE-Leimen, Various dates New approaches to study ubiquitin and ubiquitin-like modifications Nuclear function and cell fate choice 1 June and 1 October 2016 The EMBO Meeting IT-Alghero, 17 – 24 September 2016 GR-Kyllini, 18 – 22 September 2016 DE-Mannheim, 10 – 13 September 2016 For further information see: The modularity of signalling proteins Non-coding RNA in infection www.embo.org/funding-awards/ DE-Würzburg, 18 – 24 September 2016 and networks AT-Seefeld in Tirol, 20 – 25 September courses-workshops For a complete and Targeted NGS in patients with cancer, 2016 mendelian or complex diseases up-to-date list PL-Krakow, 19 – 23 September 2016 Glycosylation in the Golgi complex IT-Vico Equense, 24–28 October 2016 of EMBO events Modelling cellular processes in space and time please go to FR-Hyères, 15 – 22 October 2016 events.embo.org

16 EMBOencounters | Spring 2016 | [email protected] ©2016 EMBO RESEARCH HIGHLIGHTS – AWARDS Awards of Excellence A Good Read – Publications from the EMBO MEMBERS EMBO Community Louis-Jeantet Prize for Cloëtta Foundation based in Academy of Medical Sciences The sexual identity of adult Isoform diversity in the Arp2/3 Medicine Zurich since 1974. Ewan Birney, Sarah Bray, intestinal stem cells controls complex determines actin Andrea Ballabio and John Elaine Dzierzak, Matthew organ size and plasticity filament dynamics Gregori Aminoff Prize Diffley have been announced Freeman, Kairbaan Hodivala- Irene Miguel-Aliaga (EMBO Young Michael Way (EMBO Member), winners of the 2016 Louis- The Royal Swedish Academy Dilke, Laurence Hurst, Sarah Investigator), Bruno Hudry (EMBO Jasmine V. G. Abella (EMBO Fellow) Jeantet Prize for Medicine. of Sciences has awarded Teichmann and Michael Advanced Fellow) and colleagues and colleagues They will both receive 700,000 the Gregori Aminoff Prize in Way have been elected to the Nature | 18 February 2016 Nature Cell Biology | 14 December 2015 Swiss Francs (approx. 670,000 crystallography 2016 to Poul Fellowship of the Academy of doi:10.1038/nature16953 doi:10.1038/ncb3286 Medical Sciences in recogni- Euros) for their “fundamental Nissen, Aarhus University. Poul Divergent evolution of vitamin B9 Ankyrin-mediated self-protection tion of their excellence in biological research that is Nissen is the first Dane to binding underlies Juno-mediated during cell invasion by the research and innovative appli- expected to be of considerable receive the Aminoff Prize. This adhesion of mammalian gametes bacterial predator Bdellovibrio significance for medicine”. prize is intended to reward an cation of scientific knowledge. Luca Jovine (EMBO Young bacteriovorus individual contribution in the German Cancer Prize Investigator) and colleagues Andrew L. Lovering (EMBO Young Gottfried Wilhelm Leibniz field of crystallography. Prize Johannes Zuber has received Current Biology | 8 February 2016 Investigator) and colleagues doi:10.1016/j.cub.2015.12.034 Eraldo Antoni Award for the German Cancer Prize Nature Communications | 2 December 2015 Frank Bradke, Emmanuelle doi:10.1038/ncomms9884 Charpentier and Marina Porphyrin Chemistry 2016 in experimental cancer A 3� UTR-Derived Small RNA research. The prize worth Rodnina are among the ten Maurizio Brunori has been Provides the Regulatory Synthetic lethal targeting of 22,500 Euros is awarded Noncoding Arm of the Inner oncogenic transcription factors researchers who received the selected as the winner of the annually by the German Membrane Stress Response in acute leukemia by PARP 2016 Leibniz Prize. Each of the 2016 Eraldo Antoni Award ten winners will receive 2.5 Cancer Society and the inhibitors for Porphyrin Chemistry. The Jörg Vogel (EMBO Member) and million Euros to support their German Cancer Foundation award will be presented to colleagues Eric So (EMBO Young Investigator) future research. The Leibniz for groundbreaking work in him during the International Molecular Cell | 4 February 2016 and colleagues Prize is Germany’s most presti- experimental research, trans- doi: http://dx.doi.org/10.1016/j. Congress on Porphyrins and Nature Medicine | December 2015 gious research prize. lational research and clinical molcel.2015.12.023 doi:10.1038/nm.3993 Phthalocyanines to be held in research in oncology. Liliane Bettencourt Prize for Nanchino, China on July 3 – 8, Dual RNA-seq unveils noncoding A gut-vascular barrier controls Life Sciences 2016. EMBO YOUNG RNA functions in host–pathogen the systemic dissemination of INVESTIGATORS interactions bacteria Thomas Lecuit is the 2015 The Marcel Benoist Prize Jörg Vogel (EMBO Member) and laureate of the Liliane Friedrich Miescher Award Elisabetta Dejana, Maria Rescigno colleagues Bettencourt Prize for Life Laurent Keller is the winner (EMBO Members) and colleagues Petr Broz has been awarded Nature | 28 January 2016 Sciences. The prize (300.000 of the Marcel Benoist Prize Science | 13 November 2015 the 2016 Friedrich Miescher doi:10.1038/nature16547 doi: 10.1126/science.aad0135 Euros) has been awarded 2015. This prize has been awarded every year since Award by the Swiss Society annually since 1997 to for Molecular and Cellular A structured interdomain linker Histone H1 couples initiation 1920 to scientists working in a European researcher Biosciences (SSCMB). The directs self-polymerization of and amplification of ubiquitin Switzerland who have made recognized by the scientific 38-year-old infection biologist human uromodulin signalling after DNA damage community for the quality of “the most useful scientific receives this award for his Luca Jovine (EMBO Young Niels Mailand (EMBO Young discovery or study, in particular international publications, the work on the inflammasome, Investigator) and colleagues Investigator) and colleagues leadership in his or her field, a in disciplines which are of a cytosolic signaling complex Proceedings of the National Academy of Nature | 21 October 2015 promising project and mentor- significance for human life.” in the body's cells, which is Sciences | 25 January 2016 doi:10.1038/nature15401 ing qualities. important for the detection doi:10.1073/pnas.1519803113 Knight in the Legion of Immunosurveillance of the Liver and restriction of bacterial Ernst Jung-Prize Honour Touch, act and go: landing and by Intravascular Effector CD8+ pathogens. operating on nucleosomes Hans-Georg Rammensee Isabelle Mansuy was elected T Cells Titia K Sixma (EMBO Member), was awarded the 2016 Ernst Knight in the Legion of Honour Irene Joliot-Curie Young Matteo Iannacone (EMBO Young Andrea Mattevi (EMBO Young Jung-Prize for his ground- by the French Minister of Female Scientist Prize Investigator) and colleagues Investigator) and colleagues breaking work on the molecu- Research and Education. The Cell | 23 April 2015 Rut Carballido-Lopez won The EMBO Journal | 19 January 2016 lar structure of cell surface order Legion of Honor was doi: http://dx.doi.org/10.1016/j. the Irene Joliot-Curie Young doi:10.15252/embj.201593377 cell.2015.03.005 peptides. The Ernst Jung Prize established by Napoleon Female Scientist Prize for Medicine, worth 300,000 Bonaparte in 1802 and is the for 2015 from the French Transcriptome-wide PredictSNP: Robust and Euros, is one of Europe’s high- highest decoration in France. Academy of Sciences and the distribution and function of RNA Accurate Consensus Classifier for est research prizes. French Ministry of Education hydroxymethylcytosine Prediction of Disease-Related Gagna A. & Ch. Van Heck Prize and Research. François Fuks (EMBO Member) and Mutations Genetics Society of America 2015 colleagues Jiri Damborsky (EMBO/HHMI Medal Max Delbrück Prize of the Steve Jackson was awarded Science | 15 January 2016 Scientist) and colleagues University of Cologne doi:10.1126/science.aac5253 Detlef Weigel has been the Gagna A. & Ch. Van Heck PLOS Computational Biology | 2014 awarded the Genetics Society Thorsten Hoppe received the doi: 10: e1003440 Prize 2015, "for his cardinal Targeting aberrant epigenetic of America Medal for his 2016 Max Delbrueck Award for contributions related to networks mediated by PRMT1 outstanding contributions to outstanding achievements in BOOKS cellular events that detect, and KDM4C in acute myeloid the field of genetics in the last aging research. The University signal the presence of and leukemia Microbial Biochemistry (fourth 15 years. of Cologne annually grants this repair DNA damages". The edition) prize to senior researchers for Eric So (EMBO Young Investigator) triennial prize of 75,000 Euros Georges Cohen (EMBO Member) Alice and C.C. Wang Award in outstanding research within and colleagues is funded by the Fonds de la Springer | 2016 Molecular Parasitology the last five years. Cancer Cell | 11 January 2016 Recherche Scientifique-FNRS, doi: 10.1016/j.ccell.2015.12.007 ISBN 978-94-017-7579-3 Mike Ferguson has been based in Brussels, Belgium. named as the recipient of Young Investigator Award The transcriptional coregulator Molecular Biology of Assemblies and Machines the 2016 Alice and C.C. European Academy of Matteo Iannacone has PGC-1β controls mitochondrial Wang Award in Molecular Microbiology been awarded the Young function and anti-oxidant Wolfgang Baumeister (EMBO Parasitology. The prize, Investigator Award by the defence in skeletal muscles Member) et al. Judith Armitage, Cecilia awarded by the American European Association for the Daniel Metzger (EMBO Member) Garland Science | 15 March 2016 Arraiano, Antje Boetius, Society for Biochemistry and Study of the Liver (EASL). and colleagues ISBN 9780815341666 Molecular Biology (ASBMB), Carmen Buchrieser, Nature Communications | 17 December 2015 The Society of Genes recognizes scientists who are Emmanuelle Charpentier, National Latsis Prize doi:10.1038/ncomms10210 making seminal contributions Guy Cornelis, Antoine The National Latsis Prize 2015 Itai Yanai (EMBO Member) et al. to the field. Danchin, Dusko Ehrlich, Jeff has been awarded to Richard A transcription-independent Harvard University Press | January 2016 Errington, Urs Jenal, Regine Benton for his work on the epigenetic mechanism is ISBN 9780674425026 Cloëtta Prize Kahmann, Bruno Lemaitre, fruit fly's sense of smell. Worth associated with antigenic Dominique Soldati-Favre Colin Murrell, Peter Sebo, 100,000 Swiss Francs, the switching in Trypanosoma brucei has been awarded the 2015 Jörg Vogel and Arturo prize is awarded for excep- Luisa Miranda Figueiredo Cloëtta Prize. Worth 50,000 Zychlinsky have been elected tional scientific achievements (EMBO Installation Grantee) and Swiss Francs, the prize is to the European Academy of by a researcher under the age colleagues awarded annually by the Max Microbiology. of 40 working in Switzerland. Nucleic Acids Research | 15 December 2015 doi: 10.1093/nar/gkv1459

YOUNG INVESTIGATORS 2015 INSTALLATION GRANTEES 2015 Andrea Alimonti Nolwenn Jouvenet Çağlar Çekiç Yongsoo Park Molecular Medicine Microbiology, Virology & Pathogens Immune cell regulation Neurotransmitter release in psychiatric CH Oncology Institute of Southern FR Institut Pasteur, Paris US La Jolla Institute for Allergy and disorders Switzerland (IOSI), Bellinzona Immunology DE MPI for Biophysical Chemistry, Chiea Chuen Khor TR Bilkent University, Ankara Göttingen Marek Basler Genomic & Computational Biology TR Dokuz Eylul University, Izmir Microbiology, Virology & Pathogens SG Genome Institute, Singapore Sebastian Glatt CH Biozentrum, University of Basel Translational control in neurodegen- Umut Şahin Romain Koszul erative diseases PML nuclear bodies Isabel Bäurle Genome Stability & Dynamics DE EMBL, Heidelberg, Germany FR Université Diderot (Paris 7), Paris Plant Biology FR Institut Pasteur, Paris PL Jagiellonian University, Krakow TR Boğaziçi University, Istanbul DE Universität, Potsdam Yogesh Kulathu Maria Górna Ondřej Štěpánek Priscille Brodin Signal Transduction Structural studies of RNA-binding Antigenic signalling and fate decisions Microbiology, Virology & Pathogens UK University, Dundee proteins in T cells FR Institut Pasteur, Lille Gaelle Legube AT CeMM, Vienna CH University Hospital Basel, CH Clemens Cabernard Genome Stability & Dynamics PL University of Warsaw CZ Institute of Molecular Genetics, Prague Cell Cycle FR Laboratoire de biologie cellulaire et Aşkın Kocabaş CH Biozentrum, University of Basel moléculaire du contrôle de la Information processing in the nervous prolifération (LBCMCP), Toulouse Karin De Visser system Immunology Naoko Mizuno US Harvard University, Cambrıdge NL Netherlands Cancer Institute, Structural Biology & Biophysics TR Koç University, Istanbul Amsterdam DE MPI für Biochemie, Martinsried EMBO ADVANCED FELLOWS 2015 Thijs Ettema Paola Picotti Evolution & Ecology Systems Biology Bharat, Tanmay Kato, Saul SE Uppsala University CH ETH Zurich High-resolution in situ imaging of Decision making by nonlinear brain plasmid segregation by the ParMRC dynamics in C. elegans Ana Eulalio Nicolas Plachta system AT Research Institute of Molecular RNA Development UK Medical Research Council Laboratory Pathology, Vienna DE University, Würzburg SG Institute of Molecular and Cell Biology of Molecular Biology, Cambridge A*STAR, Singapore Martincorena, Inigo Pablo Huertas Hudry, Bruno Unravelling the extent of somatic Genome Stability & Dynamics Jochen Rink Cellular context of sex chromosome mutation in normal tissues and its role ES CABIMER, Sevilla Development regulation in the progression to cancer DE MPI für Physik komplexer Systeme, Matteo Iannacone UK Medical Research Council Clinical UK Wellcome Trust Sanger Institute, Dresden Immunology Sciences Centre, Imperial College Hinxton IT San Raffaele Institute / DIBIT, Milano Robert Ryan London, London Microbiology, Virology & Pathogens Shalev Itzkovitz Ichim, Gabriel UK University, Dundee Cell & Tissue Architecture Revisiting old paradigms: Mitochondria IL Weizmann Institute of Science, Alessandro Vannini and caspase activation as oncogenic Rehovot Structural Biology & Biophysics drivers UK Institute of Cancer Research, London UK Cancer Research UK Beatson Institute, Martin Jinek University of Glasgow, Glasgow RNA CH University of Zurich

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