The EMBO Meeting 2013 Epigenetics in Asia Science Meets Policy In

AUTUMN 2013

ISSUE 25 encounters

page 3 Science meets policy in Amsterdam

pages 3 | 10 | 11 The EMBO Meeting 2013 e 21 pag The unseen world

page 6 Epigenetics in Asia ©M. Oeggerli

Editorial EMBO announces the launch of Interview EMBO Member Olivier Voinnet Feature A research team in Switzerland led EMBO Press, a new editorially independent discusses RNA silencing and a new antiviral by EMBO Member Paulo Dotto is looking publishing platform for the development response discovered in mammals. at the origins and genetics of skin cancer. of EMBO scientific publications. PAGE 2 PAGE 4 PAGE 7

www.embo.org COMMENTARY

Inside scientific publishing Announcing EMBO Press Previous articles in EMBOencounters explored important topics in scientific publishing related to peer review, editorial processes and the merits of journal impact factors in assessing research. This month we are excited to announce the launch of EMBO Press, a new editorially independent publishing platform that will allow us to develop further EMBO scientific publications and build on the established strong reputation of our journals.

nline journals are no longer constrained New partnership Further details about EMBO Press are available to static PDFs and web presentation that After ten fruitful years with Nature Publishing at http://www.embo.org/embo-press and we Omimic the appearance of printed arti- Group, we have decided to collaborate with Wiley encourage you to visit the new journal websites cles. As a publisher of scientific research, EMBO and HighWire Press to support the EMBO Press that will be available from December. strives to be at the forefront of new technologies platform. EMBO Molecular Medicine has been We are continually looking for ways to add that will allow research data to be discovered published in cooperation with Wiley since 2009. maximum value to scientific research, and are more easily through new search mechanisms, Wiley, one of the leading international publishers always eager to hear feedback from you. and to be published in a way that will allow of academic content, will now support editorial their broader use – an essential consideration for production and international marketing of the Maria Leptin all scientists, given the rapid expansion of the four EMBO scientific journals. HighWire Press Director EMBO research literature. We will launch EMBO Press will provide an innovative online platform for in December to further these goals. the journals. Access to the Drupal open source Bernd Pulverer EMBO Press is a new publishing platform content management system of HighWire Press EMBO Head of Scientific Publications for The EMBO Journal, EMBO reports, Molecular opens up new possibilities for innovation in areas Thomas Lemberger Systems Biology and EMBO Molecular Medicine. like data presentation, semantic interlinking, EMBO Press will embody our editorial independ- article level metrics and mobile web interfaces. EMBO Deputy Head of Scientific Publications ence and is founded on the principle that scien- Many leading journals in the life sciences rely on tific publishing should be more transparent, fair, HighWire Press and we look forward to cooperat- and ethical; it must support a reliable, reproduc- ing with these journals on technology and policy ible literature. developments. EMBO Press is part of the transformation of Following the launch of EMBO Press, our four research articles into enriched and accessible journals will continue to serve their individual records of research data that will help scientists communities, selecting and presenting some make new discoveries. Our four journals will of the very best research for publication from benefit from a fresh and dynamic design that authors all over the world. Authors and readers will maximize online functionality and access. will benefit from the shared policies, technol- The enhancements will include publication and ogy, and further innovations that EMBO Press persistent storage of source data as well as the provides, including our Transparent Process, curation of published figures with the addition of which has enhanced the reliability and account- computer-readable metadata. EMBO Press will ability of the editorial process. All the finan- also include resources such as visually enhanced cial benefits from our publishing activities will guidelines to help write a successful paper and continue to support the activities of EMBO and for image and data processing. the scientific community.

Highlights from the EMBO Meeting 2013 From lipid rafts to the role of science in policy making

The EMBO Meeting 2013 took place the moons of Saturn that appears to have liquid health by influencing changes in the composition water under its surface. of the microbiome of an individual. Clear differ- at the Amsterdam RAI Exhibition The EMBO Meeting included 20 concur- ences in the makeup of the gut microbiome exist and Convention Centre in The rent sessions that spanned topics such as cell for individuals from different countries. In some Netherlands on 21– 24 September membranes, stem cells, cancer genomics and studies, these differences have been shown to optogenetics. Three plenary sessions included reflect different usage patterns for antibiotics in 2013. The meeting brought together talks about the organization of the cytoplasm and each country. more than 1000 scientists from the roles of health and disease of ubiquitin signal- On the second day of the meeting, Vishva across the world to talk about the ing and infectious proteins. Dixit from Genentech gave a plenary lecture. Dr. In a plenary session, David Eisenberg from Dixit helped to define many of the key molecu- life sciences. the Institute for Genomics and Proteomics at The lar events that take place during programmed University of California Los Angeles Department cell death. His current research interests include ai Simons, Research Group Leader and of Energy presented two different ways of think- how inflammation can contribute to cancer and Director Emeritus of the Max Planck ing about the structures of amyloid fibres. Some other diseases. In his talk, he described the role KInstitute of Molecular Cell Biology and diseases are clearly related to the presence of of the protein deubiquitinase BAP-1 as a tumour Genetics in Dresden, Germany, gave the opening these fibres. The work of his team helps to define suppressor and summarized some of the essential lecture. In the introduction to his talk, he empha- relationships between structure and activity and genes regulated by this protein that may contrib- sized the excitement of doing science as well as is also useful in designing new drugs. Eisenberg ute to disease. The loss of function of BAP-1 has some of the challenges. Simons helped establish described a structure-based procedure for design similar consequences in mice and humans and is The EMBO Meeting as part of the regular calendar of non-natural peptides that inhibit fibre growth linked to the development of hereditary cancer of events for scientists. In his lecture, he talked as well as a combined structure and computa- syndrome. about lipid rafts and the way that changes in tional procedure for the identification of small In the Science Policy session, Anne Glover, membrane structure can influence cell function. molecules that inhibit amyloid toxicity. Chief Scientific Adviser to the European Chris McKay, a research scientist at NASA In a session on new methods in genomics, Commission president Manuel Barroso, discussed Ames Research Center in the United States, Peer Bork from EMBL described a systemic anal- the role of science in policy making. Scientists gave the special lecture on the second day of ysis of the human gut microbiome. He summa- have an “absolute obligation” to translate their the meeting. McKay provided an update on the rized work that has identified three types of research to the public, said Glover speaking at Mars Curiosity Rover mission and also gave his microbial communities that exist in the gut of the meeting. The session was organized by the thoughts on other planets that might be able humans and provided an update on some of the EMBO Science Policy Programme, and moderated to support life. “The Viking mission inspired latest results arising from large-scale studies that by Michele Garfinkel, manager of the Programme. me to get involved in looking for life on other are being conducted in several countries across For further highlights of The EMBO Meeting 2013 planets,” said McKay. “Beyond Mars, one of my different continents. Microbial markers offer see pages 10 and 11. favourite candidates in the search for life in our considerable potential as diagnostic tools. In Solar System is Enceladus.” Enceladus is one of the future, it might also be possible to improve

Poster session at The EMBO Meeting 2013 ©The Maarten Schuth EMBO Meeting | Photo by

flies and even, possibly, mammals. Amplification of RNA silencing was also discovered and char- Constructive interference acterized in plants. Many people do not realize that Dicer was first identified in a plant genetic Olivier Voinnet is Professor and Chair of RNA Biology at the Swiss screen. Even the name ‘ARGONAUTE’, which Federal Institute of Technology Zürich as well as Directeur de recherche defines a universal class of RNA silencing effec- détaché du Centre National de la Recherche Scientifique (CNRS), tor proteins, stems from the squid-like phenotype of an Arabidopsis mutant. France. In 2009, he was awarded the EMBO Gold Medal for his work on RNA silencing in plants. In EMBOencounters, he talks to Barry Whyte In 2002, you set up your first laboratory in Strasbourg, France. What was the biggest about his career and recent papers in Nature Genetics and Science. challenge in building up your research group? I do not recall many big challenges but you tend to forget the difficulties when you are hungry to test your hypotheses and explore new How did you first get involved in gene genes and regulate cellular gene expression. They ideas. I chose the Institut de Biologie Moléculaire silencing research? were found in many organisms, including plants, des Plantes in Strasbourg because I knew the Before my position at the CNRS in 2002, I although for some reason the plant community infrastructure was there to conduct the type of worked with David Baulcombe, who is now was a bit slow to hop onto the “microRNA train.” research I had in mind. I also benefited from a Professor of Botany at the Department of Plant Small RNAs were breakthrough of the year in CNRS incentive, called ATIP, which provides some Sciences at the University of Cambridge. When I Science in 2002, but, from my perspective, the financial support to young principal investigators. joined David’s lab in 1996, very little was known siRNA and miRNA breakthroughs had already I was very lucky to attract talented postdoctoral about gene silencing; some people even thought it been made many years before: there is a big researchers and students so that the laboratory was an artefact of transgenesis. But we managed difference between making the key discovery and did very well from an early stage. We received to develop a model system that helped work out generalizing a discovery. There are some interest- many awards and scientific prizes and this some mechanisms and uncover a universal role ing historical perspectives to be made about this created a foundation for further discoveries. The for RNA silencing in antiviral defence. Our recent field in this respect. Agence National de la Recherche (ANR) was also findings in mammals make me more inclined to created at the time, and for many French scien- believe that defence against viruses and transpo- How important has work in plants been to tists this was a god-send: for the first time, French sons constitutes the primordial function of RNA the understanding of how RNA interference research was provided with a credible, competi- silencing across all kingdoms of life. works in mammals? tive funding scheme. Particularly important were The discovery of siRNAs in David’s lab is the open-calls, the “ANR Blanc,” which allowed This was before we knew the identity of certainly, in my mind, the most important contri- funding of basic science. The ERC system was small interfering RNAs or microRNAs? bution of the plant work to the whole field. For also created at this time and our team benefited Yes. Small interfering RNAs or siRNAs were the first time, readily detectable molecules, the from the first competitive grants awarded in 2008. discovered in David’s group at the Sainsbury siRNAs, could be used to ascertain, initially at This was an incredibly productive time where we Laboratory in Norwich, England, in 1998, right in least qualitatively, that RNA silencing was at grew to a team of more than 25 researchers and the middle of my Ph.D. These are the infamous work in a tissue or under specific conditions. expanded our research into mammalian systems. small double-stranded RNA molecules, typically Before siRNAs were discovered, all we could 20-25 base pairs in length, that provide sequence do was measure the loss of mRNAs, which is And then you moved to Switzerland? specificity to the whole mechanism of RNA inter- not very useful to characterize a process. Using Yes. I had exhausted all credible and legal possi- ference. We rapidly realized that virus-derived siRNAs as molecular markers expedited the eluci- bilities to maintain a group of this size in France siRNAs accumulate in virus-infected plants and dation of the basic mechanism of RNA silencing. when a clear opportunity presented itself at the that these molecules underlie the specificity of This was convincingly done in animal model Eidgenössische Technische Hochschule Zürich the antiviral immune system we had just discov- systems, mainly Drosophila. The same basic (ETH Zurich). I asked the CNRS for a “détache- ered. I have fond memories of this time and mechanism was found to function in mammalian ment” using a unique prerogative of permanently particularly remember the perseverance of Dr. cells where it was and continues to be studied employed French researchers. My move coincid- Andrew Hamilton, the postdoctoral researcher in from a gene regulatory standpoint in the frame- ed with the decline of the ANR, where bureau- charge of the siRNA project. He was absolutely work of miRNA-mediated regulation. cracy, lobbying and an increasing emphasis on convinced that antisense molecules had to be Other key concepts that emerged from our applied science had progressively supplanted the involved in the process and he considered all plant work included the notion that many plant original, highly praised ambitions of this agency. possibilities to eventually find them, even though viruses encode suppressors of RNA silencing, as I suppose the financial crisis that hit France and they were such tiny molecules. This tenacious is most likely the case for most invertebrate virus- so many countries did not help, but there are and uncompromising attitude remains one of es. These viral suppressors form a large array of still inexplicable decisions that were taken about my greatest inspirations in science, alongside the proteins that have proved to be very useful tools the function and scope of funding for the ANR. incredible support and freedom I received from to dissect the silencing mechanism itself. We and Given the more recent constraints imposed on David to conduct my research at an early stage. others also found, very early on, that RNA silenc- the employment of research staff in state-funded I was very fortunate to be there at the right time ing moves between cells and over long distances institutions, I think the current conditions deter with the right tools. in plants and we showed how this process forms even the most motivated of French researchers, It was really in the early 2000s that microRNAs the systemic arm of antiviral silencing, emphasiz- something I witness directly in our struggle to were recognized as a distinct and large class of ing further its analogy to an immune system. But maintain a laboratory in Strasbourg. But there is biological regulators, even though the first micro- the plant contribution to the RNA silencing field still hope: France hosts some of the brightest and RNA and its target had been reported many years went well beyond antiviral defence. In particu- innovative minds and I never cease to be amazed before in Caenorhabditis elegans, thanks to the lar, the phenomenon of small RNA-directed of how much is achieved with so little. seminal work of Victor Ambros and, later, Gary DNA methylation and chromatin modification The level of support and trust given by Ruvkun. microRNAs are similar in size to small was discovered and extensively characterized in Switzerland to its researchers is staggering and interfering RNAs and processed by the same plants, and this created a whole field of investiga- notable at all stages of a scientific career. The enzyme, Dicer. They are encoded by endogenous tion with important ramifications in fission yeast, system is highly competitive and entirely based

4 EMBOencounters | Autumn 2013 | [email protected] ©2013 EMBO INTERVIEW on merit, something I also see produced by viruses, the mole- within the ETH Zurich itself. cule that initiates antiviral RNA The strong support from Swiss silencing in plants and inverte- funding institutions is also inter- brates, activates innate immune twined with a clear vision that pathways unique to vertebrates. exploratory and applied scienc- These pathways promote the es do reinforce one another, and non-specific antiviral interferon that there is space for both. response, which most people consider so potent that it prob- What has your recent work ably rendered RNA silencing focused on? superfluous in mammals. This We have many interesting argument was fuelled by the projects brewing in the lab, negative results of several labs which reflect the diversity of exploring the accumulation of talented people who contribute virus-derived siRNAs in virus- to my laboratory. Surprisingly, infected mammalian cells. We defensive roles for RNA silenc- provide in the Science paper ing have been somewhat over- several key reasons why antivi- looked in mammals over the Olivier Voinnet ral RNAi has remained elusive years. I say surprisingly because ©Alejandra Manjarrez so far in mammalian cells. One our initial findings on plant antiviral silencing from a single-copy transposon. We could also reason pertains to the differentiated versus multi- were later corroborated almost identically in evaluate the significant contribution of the mobi- potent state of cells. Multipotency seems to corre- invertebrates, including insects, and, more recent- lization of this transposon to the genetic diversifi- late with poor interferon signalling and a toler- ly, in C.elegans; whether, likewise, defensive RNA cation of its host before the transposable element ance to long double-stranded RNA accumulation. silencing persisted in mammals is a legitimate became silenced permanently. This is a heavy- The second reason pertains to the use of highly question to ask. We have approached this ques- duty piece of work, full of genetic tricks and elab- virulent viruses, which, as shown previously by tion from two major angles that we had already orate molecular biology experiments. We took the others and our group effectively suppress RNA taken in plants: antiviral defence and mainte- time to design our experiments very meticulously silencing in plants and invertebrates. It seems nance of genome integrity through transposon and we set the bar very high to decipher the obvious that you cannot use a tool to probe a taming. Unlike most other researchers working whole thing from A to Z. I know our community phenomenon that is coincidently suppressed by on differentiated cells, I became convinced that appreciates this paper and I am proud of what the very same tool. We were not deterred by the multipotent or progenitor cells, which have now was achieved here, sometimes against all the negative results of others and persevered with been characterized in many tissues of developing odds. I keep telling people in the laboratory that our original idea, applying the knowledge we and adult mammals, would be primary sites of perseverance is the essence of innovative science. gained from our studies of plant model systems. defensive RNAi. We now have papers in Science1 An obvious corollary is that exploratory science We have published in Science at the same and PLoS Genetics (2) that strongly support this needs time and unconditional support, which time as a group led by my colleague and friend idea for defence against viruses and transposons. brings us back to funding. Shou-Wei Ding who has shown similar find- When I moved to Zürich we had just demon- ings using different approaches. A staggering strated that thousands of cellular small RNAs And the Science paper describes work in aspect of their work is to show that virus-derived are transported from cell to cell and over long mammals? siRNAs that immunize mice in vivo are identical distances in healthy plants. We proposed at the Yes and it is yet another example of persever- in their distribution, biochemical properties and time that this mobile component to endogenous ance. I initiated this project many years ago, at a relative proportions to the siRNAs we detect in RNA silencing could help plants to adapt their time when some colleagues were puzzled about ES cells. This implies the existence of a previ- new growth and perhaps their progenies to envi- my new interest in mouse embryonic stem cells ously unknown siRNA-based immune system in ronmental cues or stresses perceived very locally (ES cells). Thanks to a very fruitful collaboration mammals. These are real breakthrough findings, in single leaves or roots; we now have experimen- with Edith Heard at the Institut Curie in Paris, and I cannot wait to get the results of ongoing tal evidence to support this view and have also we set up the ES cell system in our laboratory, experiments conducted in my and Shou Wei’s isolated what I believe are the first components and together made some interesting observa- laboratories to uncover how, when and where of the mechanism that physically transports small tions potentially linking X chromosome inactiva- this immune system operates in mice. I think it RNAs between plant cells. Intriguing observa- tion and transposable elements. These findings is really an exciting time to be working in this tions suggest that non-cell autonomous silencing are at the origin of our current interest in how research area and we have still only scratched might also operate in mammals, a question my RNA silencing contributes to silence transpo- the surface in terms of biology and, perhaps, group is now pursuing as part of a major research sons in ES, and, more widely, in multipotent applications. project on extracellular RNAs that has just been cells. But Edith knew from the beginning that funded by the National Institutes of Health in the my real motivation to work with ES cells was References United States.(3) to implement an experimental virus infection 1. Science 2013; 342(6155):235 – 238 system because I was convinced that ES cells www.sciencemag.org/content/342/6155/235.full 2. PLoS Genetics In press. And now you have papers in Nature Genetics would be the right material to demonstrate anti- 3. Science 2013; 341(6149):947 and Science? viral RNAi in mammals. Mouse ES cells are also www.sciencemag.org/content/341/6149/947.full 4 The paper in Nature Genetics, which was unique because, unlike differentiated cells, they 4. Nature Genetics 2013; 45(9): 1029 –1039. published a month ago, describes how we were can withstand the complete removal of the RNA able to reactivate and follow, for the first time, silencing machinery, which was for me essential the whole mechanism by which Arabidopsis to conduct clear-cut genetic experiments as we eventually silences an invasive retro-element had done previously in plants to decipher the with the potential to amplify itself many times molecular underpinnings of antiviral silencing. in a genome. Essentially, we have deciphered the The role for RNA silencing in mammalian series of molecular events that lead to the silenc- defence against viruses has been hotly contest- ing of the many copies that originated initially ed mostly because long double-stranded RNA

©2013 EMBO EMBOencounters | Autumn 2013 | [email protected] 5 interview Epigenetic effects on coconut seeds Marjori Matzke, an expert in epigenetic gene silencing and former EMBO Council Member, left her institute in Austria last year to set up a new laboratory in Asia together with her husband and fellow researcher Antonius Matzke. In EMBOencounters, she talks about their new research efforts and about how her

life changed after moving across continents. © Academia Sinica

Dr. Matzke, you left the Gregor Mendel Institute for a conference I fell in love with this place. My How big is your lab? in Vienna exactly a year ago to join the Institute husband Antonius also liked it so we are very I run the lab with my husband Antonius and we of Plant and Microbial Biology at the Academia happy to have this opportunity to work and live work with six other people. Two of our postdoc- Sinica in Taipei. Did the focus of your research in Taiwan. toral researchers came with us from Vienna. The also change? Taiwanese co-workers have been a big help with It did not change too much. In Austria we Last year EMBO signed a cooperation agreement dealing with the language barrier. Now it is pretty worked on epigenetic gene silencing in plants with the National Science Council of Taiwan. smooth sailing. and specifically RNA-directed DNA methylation What role does EMBO play in Taiwanese science in Arabidopsis thaliana. This is the major small today? What do you think is the strength of your lab? RNA-mediated epigenetic pathway in plants. Here, EMBO has definitely made itself visible with In the last ten years, we have been pretty strong we have additionally started to look for variations several well-received visits. I know young scien- in carrying out genetic screening in Arabidopsis of this pathway in coconut, which is very under- tists who are interested in working in Europe and to identify the epigenetic factors involved in studied. Coconuts grow in southern Taiwan and applying for funding opportunities like the post- RNA-directed DNA methylation. Many of these we can get them at all stages of development. So doctoral fellowships made available by EMBO. factors were functionally uncharacterised before. we are dedicating more time to this “non-model” The opportunities offered by the organization are We identified functions in this pathway for a plant while still staying with the basic problem slipping into the consciousness of local scientists number of previously unknown proteins and of the epigenetic gene silencing in plants and and I am certainly doing my part to make people we found ways to set up transgenic systems that continuing our work on RNA-directed DNA meth- aware of them. allowed us to get hold of these factors. ylation in Arabidopsis. How important is the growing global In hindsight, what were the major advantages Why is coconut interesting for researchers? orientation of EMBO in your view? of changing location? It is an economically important plant, particularly Science is a global activity and I like the fact that It is stimulating to start working with coconut, a in tropical regions. And there appears to be a lot what you do is relevant beyond your small world. plant that is not typically used as a model system of action in the RNA-directed DNA methylation So I think it is important for EMBO to expand for research. We feel rejuvenated. Our labora- pathway during plant reproduction and seed beyond the European borders, to attract young tory is new, we have received the latest scien- development. Coconut has some of the largest scientists for training in Europe, and to help rein- tific equipment, and we are enjoying a different seeds in the plant kingdom so getting enough force the international rhythm of science. culture. experimental material is not a problem. At this point, very little is known about the genetics and How international is the scientific landscape in genomics of coconut. This research area is not Taipei. Is it changing? very highly populated and it is fun to work with. Slowly. In our institute there are 29 principal investigators and six of them are non-Taiwanese. What are the possible applications arising from Academia Sinica has a quota for international your research? workers. They frequently talk about international- It is possible that the factors we find in this epige- ising it more and some people definitely endorse netic silencing pathway can ultimately be modu- that idea but there are also others who would lated to change characteristics of the plant or its like to keep it more oriented towards Taiwanese seeds or make them resistant to certain stress. scientists. Taiwan is not as international as for This is of course a long-term goal for the future. example Singapore but it is more international than some other Asian countries. Why did you move to Asia? We had worked in Austria for more than 30 years Have you maintained strong links with Austrian and we were ready for something new. Asia has scientists? plenty of good places to do research. We knew We closed our laboratory in Austria, but we are that Academia Sinica is a top research institution still finishing projects with former co-workers. in Taiwan and that IPMB has a strong focus on Through websites and personal contacts I try to basic plant science. There are not so many insti- follow the events there and I am also keeping up Coconut farm in Pingtung County, Southern tutes around the world that are focused on basic with EMBO affairs. We visit regularly so we do Taiwan. The droppings from the ducks are plant science without expectations for applied not feel cut off by any means. used as fertilizer for the trees. work. When I visited Taiwan about six years ago

Dissimilarities in the susceptibility of individuals of different races to cancer are still not fully understood. Now a research team in Switzerland, with the support of the European Research Council, wants to probe deeper into the origins of squamous cell carcinoma, the second most prevalent form of malignant solid tumours in humans.

eople of different racial origin have differ- of Biochemistry at the University of Lausanne, epithelial compartment of the skin. In addition ent predispositions to cancer of the skin. Switzerland, remarked. “Many single nucleotide to pioneering work in this research area, Dotto PThe incidence of all three types of skin and copy number differences have been associat- and colleagues have now started to investigate cancer – deadly melanoma, basal cell carcinoma ed with predisposition to specific types of cancer the role of this pathway in the underlying mesen- and squamous cell carcinoma – is substantially but in most cases they result in only smaller chyme, the loose connective tissue of mesodermal higher in Caucasians compared to East Asian and increased risks of developing cancer.” origin that provides a supporting scaffold to over- Black African people. While pigmentation can The inability to account at the molecular level lying epithelial cells. “In recent work in a mouse account for the different incidence, it does not for genetic predisposition to cancer has led to genetic model and clinically derived skin samples, explain the more aggressive behaviour of squa- the rise of the phrase “genetic dark matter,” a we have shown that Notch signalling plays a role mous cell carcinoma in Asian or Black African symptom of the uncertainty and intractability of in the control of field cancerization,” remarked populations. Black Africans are also more suscep- making sense of complex cancers at the level of Dotto. Epithelial tumours are usually thought to tible to aggressive cancer of internal organs, for genes alone. Dotto and colleagues want to use an result from genetic changes in a discrete group of example the breast or prostate. The reasons for approach that combines genomic and epigenetic cells that originate from a single initial progenitor these differences in susceptibility are unclear. analyses of cancer predisposition and apply this or mother cell. These changes take place imme- Dissimilarities in cancer predisposition have to the study of skin as an experimental and clini- diately in the surroundings of normal cells. Field been attributed to environmental factors, for cal system. cancerization refers to cancer-promoting changes example lifestyle, diet, or exposure to chemi- “Our first objective is to test if the hypothesis that take place in epithelial cells and surrounding cals, but the genetic basis for such differences in that different genetic and epigenetic factors are stromal cells that occur in larger areas or fields. humans is much less understood. Now a group of linked to different expression of genes and key These larger target areas can be in the skin, oral researchers led by Paolo Dotto at the University of regulatory factors in keratinocytes and dermal cavity, lung, prostate or breast and expand as a Lausanne, Switzerland, want to take a closer look fibroblasts, specialized skin cells where changes consequence of aging. “These widespread chang- not only at genetic differences but also at chang- linked to cancer take place,” said Dotto. “Our es help explain why cancer often occurs at multi- es in gene expression due to factors not imme- second objective is to test if there are differenc- ple sites and in different locations and why after diately defined in an individual’s DNA sequence, es in the tumour-forming capabilities in these removal these tumours often reoccur”. so-called epigenetic processes. skin cells in individuals from different racial Dotto and colleagues will be looking closely In particular, they will look at the suscepti- backgrounds.” at how all these factors, genetic, epigenetic and bility of individuals of different racial origins to location, play a role in squamous cell carcino- squamous cell carcinoma. Squamous cell carci- Molecular signalling and Notch ma. What they learn from skin cancer may also noma, which is sometimes referred to as epider- Molecular signalling pathways play an essential be relevant to cancer in other organs. A new moid carcinoma, is a type of malignant epithelial role in the development of healthy skin. As in Advanced Grant from the European Research cell cancer. It shares cellular and architectural other tissues cancer can arise when these signal- Council will support the work. features of squamous cell differentiation that typi- ling pathways go awry. The Notch signal is vital cally occur in the epidermis. One of the signature for communication in skin cells and serves as a features of these tumours is the incredible diver- switch between the proliferation of epidermal sity of cells that arise from elevated levels of cell cells and differentiation. When this control point differentiation. This may explain the resilience of is compromised it can lead to tumour devel- such tumours to conventional cancer treatments opment. The function of the Notch pathway like chemotherapy and novel targeted therapies depends a lot on where the signalling events including antibody drugs or small molecules that take place. “While the function of several genes inhibit specific kinases. in the signalling network is under intense study, “A high genetic risk for cancer can produce the possible role of genetic or epigenetic modi- devastating consequences but scientific evidence fications of these genes in the predisposition to for the molecular basis underlying the genetic risk cancer is largely unexplored,” Dotto said. factors of complex cancers is in many cases lack- Attention has focused on the role of Notch Paolo Dotto ing,” G. Paolo Dotto, Professor in the Department signalling as a tumour suppressor in the ©University of Lausanne

VIDEO Upcoming deadlines Next issue EMBOencounters EMBO Keynote Lectures 1 December 2013 1 March 2014 The next EMBOencounters issue – EMBO Long-Term Fellowships Winter 2013|2014 – will be dispatched in 14 February 2014 February 2014. EMBO Courses & Workshops Please send your suggestions, contributions 1 March 2014 How to get your paper published and news, to [email protected] EMBO | EMBL Symposia http://youtu.be/XL8JsRgaWis 1 March 2014 by 10 January 2014.

©2013 EMBO EMBOencounters | Autumn 2013 | [email protected] 7 news from the embo community Science live for Russian high-school students A two-week Summer School in the Russian research centre Pushchino proved to be a life-changing event for some of the eighty high-school students in attendance. Fyodor Kondrashov, group leader at the Centre for Genomic Regulation in Barcelona, Spain, initiated the project two years ago to give young people a realistic experience of what it is like to do scientific research.

or EMBO Young Investigator Fyodor Kondrashov the summer of 2013 has been Fvery eventful. Just a few weeks after receiv- ing a starting grant from the European Research Council, he travelled to his home country Russia for a two-week summer school hosting 80 Russian high-schoolers aged 15 –17. He took charge of this project almost single-handedly for the second time – a fulfilment of his life-long dream and an “extremely exhausting task.” The students participating in the “School of Molecular and Theoretical Biology” were accom- panied by almost 60 faculty members. Most of these were graduate and postdoctoral students; a few group leaders also accepted the invita- tion to attend. Having genuine team leaders in the programme was an important part of the concept. “The idea is to make the kids partici- pate in real science rather than just play like they are doing science,” says Kondrashov. EMBO Installation Grantee Marcin Nowotny was on Students collecting samples at the Oka River the faculty board as well as Long-Term Fellow ©Doris Yee Cajetan Neubauer from the California Institute and analyses at the bench – or the computer. others came from rather impoverished families. of Technology in Pasadena, United States. Both Each group consisted of at most ten students and 17-year-old Grigory Khimulya from Sochi said: came to Pushchino thanks to a small grant from was guided by several scientists. Lectures and “The school was of the most important events in the Howard Hughes Medical Institute. courses covered most of the modern life sciences, my life. It is hard to describe how enriching and Russia has a long tradition of extra-curricular from embryology to paleontology and from bioin- exciting it was for me.” activities at schools so it was not unusual that formatics to microbiology. The school was using The school is organized and managed by the Fyodor began teaching junior colleagues while the infrastructure of the research institutes in Dynasty Foundation, the largest private founda- still a graduate student at the University of Pushchino, a science city two hours’ drive south tion in Russia supporting science and science California at San Diego. Public engagement is of Moscow. education. In the future, Fyodor hopes to find a fantastic way for the scientists to gain impor- Cajetan’s group focused on environmental additional sponsors and perhaps even organise tant skills and to make a difference. “By the time microbiology and regularly went on field trips one season of the school in Barcelona where he the two weeks were over, we were completely to collect samples from the nearby river Oka. “I is currently working. exhausted. Yet it was an incredibly rewarding had some highly talented students from a variety For more details please visit: experience,” concludes the evolutionary biologist. of backgrounds,” he says. Some of the attendees dynastybioschooleng.wordpress.com The fourteen days in Pushchino were packed came from large cities such as St. Petersburg and full with science. Every day, the students spent Moscow, others from remote villages in Siberia. Cajetan’s group blog: emicrobio.wordpress.com two hours in theoretical lectures; the remaining Their educational background was just as diverse. five or six hours were reserved for experiments Whereas some had private school experience,

VIDEO

Fyodor Kondrashov Fyodor Kondrashov, EMBO Young Investigator and Group Leader at the Center for Genomic Regulation (CRG), talks about his science, how he benefitted from the programme and the highschool science teaching projects he is involved in. http://youtu.be/oqR6Q15NIZg On the last day of the school the students presented their research results to faculty ©Konstantin Gribov

The Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic was founded as an independent research institute in 1962. As part of the new BIOCEV centre of excellence for biotechnology and biomedicine which is being built near Prague, it is building on its many scientific achievements and looking to start new collaborations.

ike many European countries, recent years The Institute of Biology of the Czechoslovak Czech Republic and Charles University in Prague. have been challenging for the financial Academy of Sciences was established in 1953. It The goal is to establish a new European Centre Lsupport of science in the Czech Republic. In included the Department of Experimental Biology of Excellence in biomedicine and biotechnology spite of the constraints, The Institute of Molecular and Genetics, headed by Milan Hašek, one of the in the village of Vestec which is located about Genetics has continued to build on its many years joint discoverers of immunological tolerance. In 7 km from the present campus of the biomedi- of scientific progress. 1962, the Department became the independent cal institutes of the Academy of Sciences. The More than 350 employees work at the Institute, Institute of Experimental Biology and Genetics of building construction and equipment are being including over 100 scientists, 100 PhD students the Czechoslovak Academy of Science with Milan financed mainly from the European Regional and 30 undergraduates studying for diplomas. Hašek as its Director until 1970. Development Fund, which is providing approxi- Many of the senior scientists also serve as univer- The nineteen sixties were notable for the mately 80 million Euros for the project. The new sity teachers. Twenty three research groups focus institute – the “Czechoslovak immunogenetic center will host almost 600 people, including 200 on molecular and cellular immunology, molecular school” was born, represented besides Hašek by students, in 54 research teams and five research genetics, functional genomics and bioinformatics, such names as Pavol and Juraj Iványi and Jan programmes – functional genomics, cellular biol- oncogenes, molecular biology of development, Klein. An internationally renowned programme ogy and virology, structural biology and protein cell biology of the nucleus and cytoskeleton, for retroviral research was also established under engineering, biomaterials and tissue engineering, structural biology and mechanisms of receptor the leadership of Jan Svoboda. and development of therapeutic and diagnos- signalling. Well-equipped core facilities support In 1977, The Institute of Biology of the tic procedures. The building is scheduled to be all of these activities (see Box 1). Czechoslovak Academy of Sciences was formally completed by March 2015. named the Institute of Molecular Genetics of the The research programmes have already start- Czechoslovak Academy of Sciences (IMG), with ed and the project should be a major boost for Josef Říman as the Director. Subsequent years Czech biomedical research in the coming years. saw important scientific achievements includ- More information is available at ing the joint discovery of reverse transcriptase www.img.cas.cz (J. Ř íman), the discovery of virogeny (J. Svoboda), and the sequencing of one of the first viral genomes (V. Pačes). Box 1 | Core facilities and services Václav Hořejší has been the director since at the institute 2005. In 2007, the institute moved into a new building in the Prague-Krč campus of biomedi- ➔➔ Bioinformatics cal institutes of the Academy of Sciences. The ➔➔ Genomics institute also includes a modern animal facility, ➔➔ Animal house (mouse models) a conference hall with 300 seats (Milan Hašek ➔➔ Cryobank Auditorium), a kindergarten for 20 children, and ➔➔ Custom monoclonal antibody a sports facility. Several successful biotechnol- preparation ogy spin-off companies have been established in ➔➔ Cell culture media preparation recent years. ➔➔ Flow cytometry ➔➔ Histology Strength through partnerships ➔➔ Information technologies The Institute of Molecular Genetics has recently ➔➔ Light and electron microscopy been involved in a major project named BIOCEV ➔➔ Transgenic unit (Biotechnology and Biomedicine Centre of the (producing transgenic mice including Academy of Sciences and Charles University in gene knock-outs) Vestec; www.biocev.eu/en). This is a joint project ➔➔ X-ray irradiation

©Institute of Molecular Genetics of six institutes of the Academy of Sciences of the

Table 1 | Research highlights Research area InvestigatorS Focus Journals Molecular genetics Jiří Forejt Identification of Prdm9 as the first mammalian Science 2009;323(5912):373 et al. speciation gene responsible for the phenomenon of PLoS Genet. 2012;8(11):e1003044 male hybrid sterility Proc Natl Acad Sci U S A 2013;110(6):E468 Cell biology Vladimír Kořínek Identification of novel regulators of Wnt signaling Dev Cell 2006;11(2):203 et al. Nucleic Acids Res 2009;37(9):3007 Gastroenterology 2013;144(2):381 Developmental biology Zbyněk Kozmik Mechanisms of eye development Proc Natl Acad Sci U S A 2008;105(26):8989 et al. Dev Biol 2009;334(1):31 Cell biology David Staněk Spliceosome assembly, dynamics of Cajal bodies J Cell Biol 2010;191(1):7 et al. formation Mol Biol Cell 2011; 22(4):513 Cancer cell biology Libor Macůrek Role of Wip1 phosphatase in the DNA damage response J Cell Biol 2013;201(4):511 et al. and predisposing to cancer

Keynote lecture on Wnt signalling, stem cells and cancer

EMBO Gold Medal winner Thijn Brummelkamp Meet the Speaker session ©The Maarten Schuth EMBO Meeting | Photos by The EMBO Meeting – highlights hijn Brummelkamp was awarded the EMBO Brummelkamp and his research group also inves- NKI. He also holds an appointment as Adjunct TGold Medal 2013 at The EMBO Meeting tigate how viruses and bacteria make their ways Principal Investigator with the CeMM Research in Amsterdam, The Netherlands, on Sunday into mammalian cells. Center for Molecular Medicine of the Austrian September 22. Brummelkamp received his award Thijn Brummelkamp received his PhD from Academy of Sciences. for work to accelerate the genetic analysis of Utrecht University in 2003 for his work at the he EMBO Meeting 2013 included a wide range human disease. In 2002, Brummelkamp devel- Netherlands Cancer Institute (NKI). He did not Tof talks from scientists from many scientific oped an inexpensive method to permanently pursue formal postdoctoral training but imme- disciplines. In a keynote lecture, Hans Clevers, inactivate large numbers of genes by the use of diately accepted a position to establish his own Professor of Molecular Genetics at the Hubrecht RNA interference. This breakthrough involved research programme as a Whitehead Fellow at the Institute, The Netherlands, and President of the the development of a new short hairpin RNA prestigious Whitehead Institute for Biomedical Royal Netherlands Academy of Arts and Sciences, vector system (pSUPER) that directs the synthe- Research, Massachusetts, Cambridge, United discussed the relationship between Wnt signal- sis of small interfering RNAs in mammalian cells. States. In 2011, he moved his laboratory to the ing, Lgr5 stem cells and cancer. In his talk, he

VIDEO

The EMBO Meeting – Focus on Hans Clevers “It’s up to us, to the scientists, to explain to all the parties involved what stem cells are and how to use safely.” Hans Clevers talks to Thomas Lemberger, Chief Editor Molecular Systems Biology about the connection between stem cell and cancer research as well as their medical implications. http://youtu.be/iKdoHLV9nag

Anne Glover

Michael Rosen

showed videos of stem cells in the intestine that three prize winners. Peter Hegemann, from the genes can lead to human cancer. In his lecture, illustrated how these self-renewing cells can Humboldt University in Berlin, and Georg Nagel, Stratton explained how all cancers are caused by give rise to all types of cells found in the intes- from the University of Würzburg, Germany, somatic mutations and he reviewed the muta- tine, including cancer cells. Clevers went on to discussed their contributions to the field of tional signatures found across different types explain that intestinal cancer is initiated by Wnt optogenetics, in particular how channelrhodop- of human cancer. Stratton currently heads the pathway-activating mutations in certain genes sin, a small algal photoreceptor, can be used for cancer genome project, an initiative that seeks such as APC (adenomatous polyposis coli). research applications. “Optogenetics is primarily to use the human genome sequence and high Deletion of the APC gene in stem cells, but not in an analytic instrument. But applications in the throughput techniques to discover disease muta- other cells of the villi, results in the formation of field of retinal prosthesis and deep brain stimula- tions and help improve cancer diagnosis, treat- cancer tumours. This finding and others support tions are on the way and might be realized soon,” ment, and prevention. In 2009, Stratton and the concept of cancer stem cells as the origin of said Hegemann speaking at the meeting. colleagues reported the first complete nucleotide cancer tumours. he third prize winner, Sir Michael Stratton, sequences of cancer genomes from a lung tumour he Louis-Jeantet Prize lecture took place on TDirector of the Wellcome Trust Sanger and a melanoma. TMonday September 23. This year there were Institute, explained how mutational processes in

VIDEO

The EMBO Meeting – How to become a Group Leader/Principal Investigator What does it take to become a Group Leader/ Principal Investigator? We asked three of the speakers, Cédric Blanpain, Carolyn Moores and Jaques Neefjes, for advice. http://youtu.be/7zSNTlzbkqc ©The Maarten Schuth EMBO Meeting | Photos by

©2013 EMBO EMBOencounters | Autumn 2013 | [email protected] 11 interview Exploring new territory Vishva Dixit is Vice President of Physiological Chemistry at Genentech. In the 1990s, Dr. Dixit and colleagues made a series of discoveries at the University of Michigan that helped define the molecular events of programmed cell death. More recently, he has been looking at the links between molecular signaling, cancer and inflammation. At The 5th EMBO Meeting in Amsterdam, The Netherlands, he talked to Barry Whyte about his career in academic and industrial research.

Let’s go back to your formative years in Kenya. very risky since as an assistant professor in the Vishva Dixit What influence did they have on you as a United States you are not tenured. But you know ©Genentech scientist? nothing ventured, nothing gained. We lived in a small town in Kenya. My parents There clearly must be pressure to develop drugs. were both physicians. They were in general prac- And your discoveries in programmed cell death So how “free” is the research? tice and they ran a small clinic. It was incred- that took place in the 1990s? Yes, there are enormous pressures to develop ibly busy. They would see very sick individuals. The problem was how does one study cell drugs. At the end of the day that is what we are Many of them had infectious disease but they death biochemically. You could induce cell about. Making medicines is a highly competitive were effectively treated with antibiotics. And that death in many ways, but none at the time were arena and we have to succeed in that. Our model always had an impression on me – the good work biochemically amenable. What happened was for being a successful pharmaceutical company is my parents were doing, and the ability of essen- that Shigekazu Nagata and Dave Goeddel had just different. I won’t say it is better or worse – it tially reviving someone at death’s door. described members of the tumour necrosis factor is just different. We believe a significant propor- receptor family – TNF receptor and FAS. If you tion of our resources should go to fundamental Did you think about medicine first as a career or engaged these receptors you got cell death. Now research. science or a combination of both? that was a biochemical handle. You could take a Well I would say it was a combination. My receptor and ask what was downstream as a way Do you think it is a privilege to be a scientist? parents had bought me this series of books from of illuminating the death pathway. How do you see this? Time Life on scientists and their work and that I think it is an enormous privilege. It is essen- influenced me. I thought it would be fascinating The results were really surprising? People were tially being paid to pursue one’s hobby and it’s to be a discoverer, an explorer, and that captivat- looking for ion channels, phosphorylation an activity that you only find in enlightened ed my imagination. events. societies. I think the quest for knowledge is a I would say that probably the most impor- common human trait. We all want to know the What made you leave Kenya and go to the tant result was the realization that there was a unknown, but it’s only in certain countries where United States? protease involved. We came around to that in a one is afforded the luxury of being able to pursue Well it was really about opportunities. I had very convoluted manner, but finally nailed it by curiosity. finished medical school in Kenya. I had complet- using a virally encoded inhibitor of caspases. ed my internship and I wanted to do biomedi- And what advice would you give to a young cal research. Unfortunately the facilities were not This was a classic inhibitor experiment? scientist interested in working in industry or a adequate for that. And that meant either going We could engage the death pathway by stimulat- university environment? to Europe or the United States. My brother and ing these receptors but what was downstream I would say that in the pharmaceutical industry sister had already settled in the United States so was a complete mystery. Around that time Bob it is very important to be a team player. You have that made it easier. Horowitz’s team had identified Ced3 as a protease to be able to play well with others in the sandbox. that was a component of the death pathway in You have to realize that the creation of a drug What was the first research project you worked the worm and this made us wonder whether an is nothing short of a miracle and it requires the on there? equivalent activity could exist in mammals, one efforts of lots of people. In the States I did a residency in pathology at responsible for death receptor-induced cell death. Washington University in St. Louis. As part of The use of a virally encoded caspase inhibitor Are you excited by the future, for your science that residency training I did my research with was the key that unlocked a Pandora’s box of and science in general? Bill Frazier in the Department of Biochemistry riches. I think there is so much more to explore, so much and we worked on thrombospondin, a protein more to find out – in terms of the pharmaceuti- involved in platelet aggregation. And then you moved to Genentech in 1997? cal industry, in terms of medicines and human It was really at the tail end of the heyday of apop- biology. And then you switched to cell death? tosis research that I moved to Genentech. I had When I worked with Bill in St Louis the work on exciting new responsibilities – at that time to VIDEO thrombospondin and extracellular matrix biology form and run an oncology programme. went reasonably well. I took a lot of that work with me to the University of Michigan. I started We hear a lot about the research culture of out as an assistant professor and my first grants Genentech. It’s very much a research driven were based on that work. We published papers. environment. Can you tell us about the culture? But it became evident to me that we were not the Research is given a very high premium. It’s a front-runners in the field. We were doing good very data driven organization and a very flat work but we were not dominant, not painting on organization. The EMBO Meeting – Focus on Vishva Dixit a larger canvas. I decided to throw caution to the http://youtu.be/FMmQnwK4_VQ winds and do something totally new. This was

The Institute for Molecular Infection Biology (IMIB) and the Research Center for Infectious Diseases at the University of Würzburg, Germany, celebrated their 20th anniversaries on the 28th of June.

he IMIB and the Research Center for Infectious Diseases (Zentrum für TInfektionsforschung or ZINF) were founded in 1993 as a means to facilitate the propaga- tion of the then new molecular tools developed in different model pathogens to understand the basis for infection by bacteria, fungi, and para- sites. While these molecular and cell-based approaches remain a central part of the institute there is now a focus on the application of new global approaches to understanding infectious ©IMIB and ZINF diseases. Hermann Bujard, Jörg Hacker and Jörg Vogel at the anniversary event “The institute is increasingly investing in new discovery-based technologies to understand the Members Fritz Melchers and Werner Goebel also Hermann Bujard, first chair of the Scientific infection process from a new viewpoint,” current attended the meeting. Advisory Board of ZINF, and former EMBO Director of the IMIB and EMBO Member Jörg “The Institute for Molecular Infection Biology Director, concluded: “It is very satisfying to see Vogel stated. “For example, several of the groups and the Zentrum für Infektionsforschung have the progress that has taken place over the past are using deep sequencing to look into the many achieved visibility and recognition for their scien- 20 years at ZINF and the IMIB. Infectious disease unexpected different roles that RNA molecules tific contributions to understand the mechanisms research and its translation to ‘the field’ are play in both infection and the immune response. of infectious disease over the past 20 years,” essential if we are to make progress in improving We are also using global approaches to try to commented Pascale Cossart. “The expertise and public health across the world, a most important understand the molecular events involved in commitment of its researchers and leadership prerequisite for peaceful developments in numer- the epigenetic basis of gene regulation and how team have helped to build a solid foundation to ous regions around the globe. Universities with complex traits such as antibiotic resistance can support infectious disease research in Europe. their genuine responsibility for research and evolve in a specific pathogen.” He added: “In This will help, ultimately, in our global efforts to education are particularly suited to meet these many cases, the institute is benefiting from new make new scientific discoveries and to improve challenges. The research programmes of ZINF approaches brought in by the young investigators the clinical understanding of infectious disease.” and IMIB are excellent paradigms for innovative that allow us to answer these important and time- In her talk, Cossart emphasized that there approaches in this crucial endeavour.” ly questions using different model pathogens.” are many interesting and in some cases crucial The central role for young independent group research options that institutions can either leaders was a fundamental goal of IMIB and ZINF pursue or choose not to investigate. “My genera- Pascale Cossart, Institut Pasteur in 1993. “From the beginning we have placed a tion of scientists has made it possible to dissect strong focus on the importance of young investi- the molecular processes associated with patho- gators in our laboratories. Our intention has been gens but the field is ready for other big discover- to give them the support they need to become ies provided that politicians and other decision independent early in their scientific career and makers are aware of the need to establish impor- to help them put in place research programmes tant links between scientific disciplines,” said that will stand the test of time,” remarked EMBO Cossart. “We must accept the fact that microbi- Member Jörg Hacker, the founding director of ology is no longer the field of Louis Pasteur or IMIB and the first spokesperson for ZINF. Robert Koch working alone with Petri dishes. The anniversary event brought together many What we need are new links with other disci- researchers from all over Europe and the rest plines including, for example, chemistry, ecology, of the world to reflect on the successes of the veterinary science and nutrition. Infection biolo- past and also to look to the future of infectious gy requires significant investment in instruments, disease research. The programme included talks informatics and bioinformatics that will allow us that provided an overview and different perspec- to store and analyse large amounts of data.” tives on current and future research on infec- The plenary lecture was given by John tion biology by Pascale Cossart, EMBO Member Mekalanos, Chair of the Department of and Professor at the Institut Pasteur, France, Microbiology and Immunobiology, Harvard and Michael Gilmore, the Sir William Osler Medical School, who described some of molecu- Professor of Ophthalmology, Microbiology and lar strategies used by bacteria to fight for superi- Immunology at Harvard Medical School. EMBO ority within a specific environmental niche. ©IMIB and ZINF

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Advanced optical microscopy Signalling to and from Visualizing biological data (VIZBI Biology of plastids: Towards a UK-Plymouth, 2 – 12 April endomembranes 2014) blueprint for synthetic organelles DE-Hegne (Allensbach), 15 – 19 March DE-Heidelberg, 5 – 7 March PL-Pułtusk, 21 – 26 June Computational biology: Genomes to systems Mechanisms of neuronal remodelling Human evolution in the genomic era: Synthetic biology of antibiotic CL-Puerto Varas, 3 – 9 April IL-Ein Gedi, 22 – 26 March Origins, populations and phenotypes production UK-Leicester, 1 – 4 April ES-Sant Feliu de Guixols, Computational structural biology Stalked alpha-Proteobacteria and 30 August – 4 September UK-Hinxton, 7– 11 April relatives: From genes to structure Telomeres, telomerase and disease DE-Ebsdorfergrund, 30 March – 3 April BE-Brussels, 30 April – 4 May Long regulatory RNAs Computational molecular evolution PL-Pułtusk, 13 – 18 September GR-Heraklion, 5 – 14 May Recoding: Reprogramming genetic Molecular biology of 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Research article Research article Research article Alzheimer’s disease protein A negative genetic interaction controls movement in mice Alternative target for breast map in isogenic cancer cell cancer drugs lines Research article Researchers in Berlin and Munich, Germany, and Oxford, United Scientists have identified higher A research team led by scientists at New muscular dystrophy Kingdom, have revealed that a levels of a receptor protein found the University of Toronto, Canada, treatment shows promise in protein well known for its role on the surface of human breast has defined a network of synthetic early study in Alzheimer’s disease controls tumour cells that may serve as a sick/lethal interactions with a set of spindle development in muscle and new drug target for the treatment query genes in a series of isogenic A preclinical study led by research- leads to impaired movement in of breast cancer. The results show cancer cell lines. This study defined ers in the United States revealed mice when the protein is absent or that elevated levels of the protein about 200 negative genetic interac- that a new oral drug shows early treated with inhibitors. The results Ret, which is short for “Rearranged tions in the isogenic cancer cell line promise for the treatment of suggest that drugs under develop- during transfection,” are associated background. By mapping negative muscular dystrophy. The results ment to target the beta-secretase-1 with a lower likelihood of survival genetic interactions in a systematic show that VBP15 decreases inflam- protein, which may be poten- for breast cancer patients in the fashion in isogenic cancer cell lines, mation in mice with symptoms tial treatments for Alzheimer’s years following surgery to remove the scientists revealed novel func- similar to those found in patients disease, might produce unwanted tumours and cancerous tissue. tions for several uncharacterized with Duchenne muscular dystrophy. side effects related to defective The scientists examined tumour genes. The study demonstrated The authors found that the drug movement. tissue microarrays of more than that differential essentiality profiles protects and strengthens muscle “Our results show that mice that 100 breast cancer patients who had derived from isogenic cancer cell without the harsh side effects lack Bace1 proteins or are treated undergone surgery to remove their lines can be used to classify genetic linked to current treatments with with inhibitors of the enzyme have tumours. Antibodies were used dependencies in non-isogenic glucocorticoids such as prednisone. difficulties in coordination and to detect the levels of Ret in the cancer cell lines. “It is becoming increasingly clear walking and also show reduced samples. In other experiments, four Improved efforts are necessary that membrane integrity and muscle strength,” remarked different cancer cell lines were used to define the functional product repair are crucial factors in muscle, Carmen Birchmeier, one of the and injected into mice to study of cancer mutations currently cardiovascular, neurodegenerative authors of the paper, Professor the effects of Ret inhibitors on the being revealed through large-scale and airway disorders. The chemical at the Max-Delbrück-Center for progress and spread of the cancer. sequencing efforts. Using genome- properties of VBP15 also suggest Molecular Medicine in Berlin, “Our findings suggest that Ret scale pooled shRNA screening potential for the treatment of other Germany, and an EMBO Member. kinase might be an attractive and technology, the researchers mapped diseases,” remarked Kanneboyina “In addition, we were able to novel alternative therapeutic target negative genetic interactions Nagaraju, DVM, PhD, the lead show that the combined activi- in selected groups of breast cancer across a set of isogenic cancer cell author of the study and a prin- ties of Bace1 and another protein, patients,” remarked Nancy Hynes, lines and confirmed hundreds of cipal investigator in the Center neuregulin-1 or Nrg1, are needed Professor at the Friedrich Miescher these interactions in orthogonal for Genetic Medicine Research, to sustain the muscle spindles Institute for Biomedical Research co-culture competition assays to Children’s National Medical Center in mice and to maintain motor and the University of Basel, generate a high-confidence genetic in Washington, DC. coordination.” Switzerland. “Initial experiments in interaction network of differentially The researchers observed that One unwanted side effect of the mice that serve as model organisms essential or differential essentiality VBP15 inhibits the transcription long-term inhibition of Bace1 might for the study of breast cancer have genes. The work of the researchers factor NF-κB, a key cell-signaling be the disruption of muscle spindle revealed that specific inhibitors suggests that many cancer vulner- molecule found in most animal cell formation and impairment of significantly block the spread of abilities remain to be discovered types that plays a role in inflam- movement. This finding is relevant cancer and decrease the number through systematic derivation of a mation and tissue damage. The to scientists looking for ways to of metastatic tumours found in the network of differentially essential authors conclude that VBP15 merits develop drugs that target the Bace1 lungs.” genes in an isogenic cancer cell further investigation for efficacy in protein. Ret inhibition decreases growth and model. clinical trials. Bace1 and neuregulin-1 (Nrg1) cooperate metastatic potential of estrogen receptor A negative genetic interaction map in to control formation and maintenance of positive breast cancer cells isogenic cancer cell lines reveals cancer VBP15, a novel anti-inflammatory and A. Gattelli, I. Nalvarte, A. Boulay et al. membrane-stabilizer, improves muscular muscle spindles cell vulnerabilities C. Cheret, M. Willem, F.R. Fricker et al. Read the paper: F.J. Vizeacoumar, R. Arnold, dystrophy without hormonal side effects doi: 10.1002/emmm.201302625 C.R. Heier, J.M. Damsker, Q. Yu et al. Read the paper: F.S. Vizeacoumar et al. Read the paper: doi: 10.1038/emboj.2013.146 Read the paper: doi: 10.1002/emmm.201302621 doi: 10.1038/msb.2013.54

the comprehensive analysis of small-molecule MRC Cancer Cell Unit transfers to metabolites using the tools of systems biology to investigate the metabolic transformation that the University of Cambridge cancer cells undergo at an early stage in carcino- genesis, with the aim of developing new diagnos- As of last October, the former Cancer Cell Unit of the Medical Research tic and therapeutic tools. Council (MRC) has become a new department within the University of Focus on translational biology Cambridge. The core funding and infrastructure support still come from the Other programmes in the unit focus on under- MRC. standing cancers with a poor prognosis, including pancreatic, lung and oesophageal, and on the he new structure – the so-called University external and commercial partners. This type of relationship between early invasion, metastasis TUnit – is being more widely adopted by the multi-disciplinary network has been particularly and the tumour microenvironment, through stud- MRC to better integrate its units into their host fruitful in the identification of chemical tools ies on human tissues and genetically engineered universities, enhance their research capacity, that modulate previously ‘undruggable’ cellular mouse models. These laboratory studies have and offer new opportunities for both collabora- targets. The programme, led by Professor Ashok already triggered tangible clinical improvements, tion and funding. As part of the University of Venkitaraman, aims to improve understanding of such as those for the early diagnosis and risk Cambridge, the new unit called the MRC Cancer the biological processes involved in the initiation stratification of oesophageal cancer by Rebecca Unit is also eligible for external funds from higher of cancer, and also offers the tangible prospect of Fitzgerald. education institutes. developing new anti-cancer agents. Commenting on the strategic alliance between The centre, which is led by EMBO Member An innovative approach integrating in vivo the University and MRC, Ashok Venkitaraman Ashok Venkitaraman, has become a leading insti- cancer models with 3D imaging, lineage trac- said, “This alliance will enhance the unit’s abil- tute for cancer research over the past decade. ing and computational biology has also been ity to deliver on its research goals, and better Today it consists of eight research programmes adopted in the programme led by Dr. Philip Jones. coordinate our work with that of other institu- covering a range of areas and involving more His group have been the first to use large-scale tions within the Cambridge Cancer Centre. The than one hundred staff. Its overall focus is on lineage tracing to quantify cell fate in vivo, utilis- unit has already made several significant contri- understanding the molecular mechanisms that ing methods more commonly found in theoreti- butions to cancer research, and we look forward underlie early steps in the genesis of epithe- cal physics for data analysis. This research has to continuing this work within the University lial cancers, and translating this knowledge into revealed how all dividing cells constitute a self- whilst retaining our strong link with the Medical clinical practice to improve cancer diagnosis and maintaining population contributing equally Research Council.” treatment, through the development of innova- to tissue maintenance, and showing how this For more information visit tive enabling technologies. homeostatic balance is perturbed during carcino- www.mrc-cu.cam.ac.uk genesis, providing important insights into new A multidisciplinary network avenues for therapy. The unit pursues a multidisciplinary approach, A recent recruit to the Unit is Dr. Christian fostering collaboration not only between its inter- Frezza, a former EMBO Long-Term Fellow. nal research programmes but also with many Frezza’s programme combines biochemistry with

Human brain tumour Professor Ashok Venkitaraman © Jo Fowler ©Hutchison Centre / MRC Research

©Hutchison Centre / MRC Research Section of the mouse oesophagus Fibroblasts and melanoma cells ©Julia Frede © Jacqui Shields

Obituary

rançois Jacob, one of the most Monod were available and they influential scientists of 20th were inserted in various combi- Fcentury molecular biology, died François Jacob nations into male and female on April 19, 2013. His name will be bacteria. The outcome of conjuga- remembered together with Jacques 1920 – 2013 tion experiments between differ- Monod and André Lwoff for unrave- ent mutants led to the model of ling the genetic control of enzyme and negative regulation: a regulator virus synthesis. These three scientific gene produces a “repressor” that pioneers were jointly awarded the blocks enzyme synthesis. These Nobel Prize in Physiology or Medicine experiments were crucial for the in 1965. Beyond science, all three were development of the messenger heavily engaged in the fight against RNA concept and the operon Nazi Germany during World War II: model. They marked a turning Monod and Lwoff in the Resistance point in how the mechanism of and Jacob on the battlefield. In 1940, protein synthesis and its regula- Jacob, a second-year medical student, tion were represented. joined de Gaulle’s Free French Forces Jacob served on EMBO in England and participated in the Council from 1963-1971. He was entire Africa campaign. Shortly after involved in many of the discus- the Normandy landing in June 1944, sions that shaped the early direc- he was severely injured by an explod- tion of EMBO, including the ing bomb. He spent many months decisions that led to the birth of in hospital and never recovered the European Molecular Biology completely. Laboratory. In his own words, Jacob had to abandon his early the road to EMBL was ‘more dream to become a surgeon because difficult than anticipated.’ He of his injuries. Nevertheless, he had remained a staunch supporter of the opportunity to begin research, as EMBO and EMBL throughout his

he recalls “in the right place at the ©Institut des Archives Pasteur/Services career. right time.” He joined Lwoff’s labora- Other major contributions in tory at the Institut Pasteur in 1950 shortly after induction. By analysing the conjugation process science included the replicon model, a paradigm the discovery of prophage induction. Jacob itself they showed that the male chromosome for DNA replication, and Jacob’s bright idea on started his research on the genetic analysis of was injected into the female at a constant rate. the role of tinkering in evolution. His legacy was lysogeny. He and Elie Wollman soon discovered This enabled them to map the order of genes and not limited to science. He was an exquisite and a new phenomenon that they called “zygotic to demonstrate the circularity of the Escherichia successful writer and his books were written in induction”: crosses between a lysogenic male coli chromosome. a highly personal and elegant style. He will be and a non-lysogenic female resulted in the induc- In 1957, an exceptionally creative collabora- remembered as one of the most original intellects tion of phage development, but not when the tion started between Jacques Monod and Jacob. of his generation. reciprocal cross was performed. This asymmetry They decided to use bacterial conjugation for Agnes Ullmann in crosses suggested the existence of a cytoplas- a genetic analysis of the E. coli lactose system. mic factor, a “repressor” that prevents phage Many mutants isolated and characterized by

Book review The Compatibility Gene MBO Young Investigator Daniel M. Davis has The Compatibility Gene takes readers on a compatibility genes in pregnancy, brain plasticity Epublished a new popular science book enti- journey spanning sixty years – from the begin- and the selection of a mate. tled The Compatibility Gene. His book is about nings of transplants and immunology leading “We built a shed at the bottom of my garden the genes of our immune system – our compat- to the edge of knowledge and current areas of and I sat there writing intensely for one year ibility genes – and about the researchers who research. and then on and off for another two years,” says have pieced together the science he describes. In parallel to the story about scientific discov- Davis. The result is an exciting science story that eries, Davis shows that a great many people made is also suitable for non-specialist readers. Daniel M. Davis’s book is an account of how these contributions. Many of them were strong human beings fight off the illnesses and diseases personalities and some lived a turbulent life. DANIEL M. DAVIS that attack us on a daily basis. It is our compat- Often one person did not appreciate another’s ibility genes that influence our susceptibility or approach. With warmth and in a light-handed resistance to multiple sclerosis, diabetes, arthritis way he writes about how the researchers have and other diseases. They are also at the heart of struggled to find the right answers and to under- our individuality. “This book is also about me stand the mechanisms that underlie our defences THE COMPATIBILITY GENE HOW OUR BODIES FIGHT DISEASE, ATTRACT OTHERS, trying to understand the differences between against diseases. AND DEFINE OUR SELVES people and why our own uniqueness is impor- The book also discusses some of the medical tant,” says the author who is professor of immu- and ethical issues that arise from our diversity in nology at the Manchester Collaborative Centre for immune system genes. The final chapter of the Inflammation Research, United Kingdom. book explores the role of the immune system and

©2013 EMBO EMBOencounters | Autumn 2013 | [email protected] 17 EMBO community Scientists must engage in creating dialogue Biosciences for Farming in Africa is the latest project involving Christopher Leaver, an EMBO Member for more than 30 years, who has been committed to creating a dialogue with the public since he started his scientific career.

oday Christopher Leaver invests much of his time and energy to reach the public Tthrough science education and communication projects. Leaver is Emeritus Professor of Plant Science at the University of Oxford, former head of the Department of Plant Sciences at the University, and Chair of EMBO Council from 1996–1997. Biosciences for Farming in Africa (B4FA) is one of the many initiatives he engages Christopher Leaver presenting a copy of B4FA essays to Kevin Urama, Executive Director of the African Technology Policy Studies Network in to address the global challenges of achieving ©B4FA food security and sustainability. The plant biologist acts as a science adviser the growing demands for food and the effects of are not about teaching. His goal is to provide in the B4FA team and is involved in its work plant diseases, pests and climate change on crop background information to journalists and to on a daily basis by providing advice, review- productivity,” says Leaver. create dialogue. The decisions are entirely to be ing articles, and contributing to workshops and A Fellowship scheme for African science jour- made by people in Africa. field visits in Africa. “Doing nothing is not an nalists is just one project offered by B4FA, which Leaver believes scientists must engage in option,” is a statement he often includes in his is supported by the United States-based John dialogue and debate: “I come from a rural back- talks and presentations. He understands it as a Templeton Foundation. In the last year, Leaver ground and tax payers in the United Kingdom call for action in the undernourished areas of East has contributed to courses and given lectures in supported my education and career from the and West Africa. “I am very worried about the four-day workshops about modern methods of moment I started school until I ended up as head consequences of increasing population, from one improving crop productivity in Ghana, Nigeria, of department at the University of Oxford.” Since to two billion over the next 40 years in Africa, Tanzania and Uganda. He emphasises the courses the development of modern molecular genetics and plant breeding – beginning with the so called Green Revolution – he has been committed to informing society and continues to do so by lecturing to students, the general public and by engagement with the media. He was a founding trustee of Sense about Science (senseabout- science.org), a British charity that promotes the public understanding of science and contributes to the successful Science Media Centre in the United Kingdom – to name just a few. “My engagement arises from a long-standing belief in ©Julia Vitullo-Martin B4FA ©B4FA communicating the relevance of science to the many challenges we face for the next generation.” Left: Professor Leaver extracting DNA with Nigerian journalist Ladidi Lucie Elukpo, one of the B4FA Fellows who works with Nigerian Guardian Newspapers. Right: Course participants visiting local farms More information on Biosciences for Farming in and research stations. Africa is available at www.b4fa.org

Translating Diabetes Molecular Machines The Complex Life Lessons from Integrating Structure, of mRNA 2014 Biophysics and Chemistry

EMBO|EMBL ORGANISERS J. Brüning, S. Herzig, M. Tschöp ORGANISERS T. Carlomagno, J. Chin, J. Puglisi ORGANISERS A. Ephrussi, N. Sonenberg, Symposia J. A. Steitz, D. Tollervey 30 April – 3 May 2014 18–21 May 2014 5–8 October 2014 Tumour Microenvironment Epithelia Frontiers in Metabolism The Building Blocks of Multicellularity From Molecular Physiology to Systems and Signalling Medicine

ORGANISERS A. J. Berns, P. P. Pandolfi, B. Pauly ORGANISERS H. Clevers, E. Fuchs ORGANISERS J. Auwerx, S. Dimmeler, T. Lemberger, V. Mootha 7–10 May 2014 27–30 August 2014 17–20 November 2014

online petition Rules on animal research in Italy Italian scientists publish an open letter to the European Commission to reverse new rules on animal research lmost ten thousand Italian scientists research in Italy and was co-initiated by EMBO forbids xenotransplantation – a widely used Ahave signed a petition addressed to the Members Jacopo Meldolesi and Giacomo method in which human tumour cells are European Commissioner for the Environment, Rizzolatti. implanted into mice to test cancer therapies – Janez Potočnik, and to a number of Italian Last summer, the Italian parliament and bans the use of animals for studying drug legislators. The petition calls on politicians approved introducing extreme restrictions on abuse. to defend the use of animals in biomedical the use of animals in research. The law now

The petition can be found at: www.salvalasperimentazioneanimale.it/sperimentazione-animale/english-version/

“The Single Cell Genomics Centre will stimulate New Single-Cell the bioinformatics research needed for interpret- Salvador Aznar ing this new type of data,” says EMBO Member Benitah wins The Genomics Centre Sarah Teichmann, who works at both institutes and is one of the six SCGC founders. “We are Metastasis Prize in Hinxton looking to establish the centre as a focal point for collaboration to accelerate the science, appli- The first winner of The Scientists at the EMBL European cations, methods and discoveries in single-cell Metastasis Prize from The genomics research.” Bioinformatics Institute (EMBL- Beug Foundation for Metastasis Single-cell genomics enables researchers to EBI) are exploring the DNA, RNA identify differences between individual cells Research is Salvador Aznar and epigenetic features of single within developing tissues. Identifying and under- Benitah from El Centre cells to better understand biology standing differences between cell types and de Regulació Genòmica, subpopulations is crucial to discover, for example, and disease. how cancer spreads or specialized cells – such as Barcelona, Spain. neurons – can be grown for use in regenerative The Metastasis Prize is awarded to cientists at EMBL-EBI and the Wellcome Trust medicine. encourage research into new ways to SSanger Institute in Hinxton, United Kingdom, impede the spread of cancer. Benitah will launched the Single Cell Genomics Centre (SCGC) www.sanger.ac.uk/research/projects/ use the award to characterize a popula- earlier this year. The centre seeks to answer key singlecellcentre tion of recently identified cells that may biological questions by exploring cellular genet- contribute to metastasis in patients with ics at the highest resolution possible. squamous cell carcinoma.

Further details are available at Sarah Teichmann and Chris Ponting, two of the six www.beugstiftung-metastase.org founders of the Single Cell Genomics Centre

50th anniversary at the University of Geneva The Department of Molecular Biology at the University of Geneva is celebrating its 50th anniversary with a symposium in Geneva, Switzerland, on June 23, 2014. The list of invited speakers includes Werner Arber (Nobel Prize 1978), Gordon Hager, Jack Greenblatt, Bruce Alberts, Harry Noller, Erich Nigg and Susan Gasser, all of whom have been affiliated with the department in the past.

©2013 EMBO EMBOencounters | Autumn 2013 | [email protected] 19 news from the embo community A new building for systems biology in Berlin Berlin, already known for systems biology research and integration of different scientific disciplines, will soon become an even more attractive place for scientists from all over the world. The Berlin Institute for Medical Systems Biology or BIMSB, headed by EMBO Member Nikolaus Rajewsky, is a young branch of the Max Delbrück Center for Molecular Medicine (MDC) and will be moving to the centre of Berlin.

he new building will provide 5400 m2 research contribute to the central themes of MDC in pursuing its scientific mission – ‘to decipher of laboratory and office space for up to research: cardiovascular and metabolic diseas- the post-transciptional regulatory code and to T25 research groups, equally distributed es, cancer, and diseases of the nervous system. integrate it with major cellular regulatory mecha- between experimental and computational areas. Technology platforms at the institute offer state- nisms.’ The laboratory of Nikolaus Rajewsky, in The building will accommodate high-tech labo- of-the-art sequencing technologies as well as collaboration with the laboratory of Ferdinand ratories, flexible workspaces and communica- mass spectrometry with high capacities for quan- le Noble and BIMSB research groups, combined tion spaces, allowing for innovative and inter- titative genome, transcriptome, proteome and biochemical, computational, and functional data disciplinary work as well as scientific exchange. metabolome analysis. Data processing, analysis to show that circular RNAs are a large class of The architectural design for the new building for and integration are supported by high-perfor- animal RNAs that often have tissue and devel- BIMSB was selected through an open competi- mance computing capacities to facilitate func- opmental stage-specific expression. Furthermore, tion and will smoothly integrate into the new life tional analysis and mathematical modeling. they could show that circular RNAs can bind science campus of the Humboldt University. It is Research projects and publications are in microRNAs, effectively interfering with microR- located in close proximity to the Charité Hospital, many cases collaborative efforts amongst BIMSB NA-mediated regulation (2). They thus proposed the German Center for Rheumatology Research and MDC research groups. They are integrated in that circular RNAs are likely a large class of post- (DRFZ), and the Max Planck as well as Leibniz national or European networks as well as inter- transcriptional regulators. These findings, togeth- Institutes. The closeness of the new, interdisci- national collaborations. Capacities and technol- er with their extreme stability, make circular plinary research building for BIMSB to the life ogy areas are expected to expand further with the RNAs interesting candidates for biomarkers and sciences of the Humboldt University and other recruitment of additional groups and the move to therapeutic agents. institutions was part of the university’s successful the new building. ‘Excellence concept’ in 2012, where, Humboldt References University, Charité Berlin (Medical University) Scientific progress 1. Nature Methods 10, 630–633 (2013) and MDC partner to develop the “Integrative In such a dynamic, high-level scientific setting, doi:10.1038/nmeth.2489 2. Nature 495, 333–338 (21 March 2013) Research Institute for Life Sciences.” The expan- scientific discoveries are almost inevitable: In doi:10.1038/nature11928 sion of the MDC to the city centre is part of the the May edition of Nature Methods, for example, innovation development strategy for life sciences the flexible computational framework, micro- in Berlin. Research and technologies of BIMSB MUMMIE, was presented to identify regulatory will substantially contribute to the developments microRNA binding sites (1). The group of Uwe in systems medicine and the scientific agenda of Ohler, in collaboration with researchers from the Berlin Institute for Health. Duke University, published a computational Currently, research groups at BIMSB are inte- approach to identify regulatory binding events by grated into the scientific activities and the campus integrating sequence with cross-linking features of the MDC in Berlin-Buch. Here, experimen- from sophisticated experimental data. Another tal, computational and high-end technological research highlight reflects the success of BIMSB

VIDEO

Focus on Nikolaus Rajewsky EMBO Member Nikolaus Rajewsky of the Berlin Institute for Medical Systems Biology talks about gene regulation, how gene sequencing is leading to personalized medicine and the passionate nature of scientists.

20 EMBOencounters | Autumn 2013 | [email protected] ©2013 EMBO news from the embo community Mysteries of the unseen world Researchers from the Biozentrum Basel headed by EMBO Member Erich Nigg contributed movie sequences based on thousands of high-resolution electron microscopy images to a National Geographic film.

he Basel team contributed barely five minutes Tto the 45-minute film Mysteries of the Unseen World – and yet it took them almost two years to develop the underlying technology. “We had to use a scanning electron microscope to image tiny organisms in IMAX quality, animated as movie sequences, in stereo and in colour – something that has never been done before,” says professor Henning Stahlberg, head of the Center for Cellular Imaging and NanoAnalytics at the Biozentrum Basel. The results are short movie sequences that offer spectacular shots into the microcosm not visible to the naked eye. The film opened in IMAX cinemas this November. The movie follows people and animals, showing the micro- and nano-worlds around them. One scene in the movie follows a group of people walking a dog in the park. A zoom into the dog’s fur shows how a tick bites him and begins to suck his blood. The journey continues into the blood stream, down to ever-smaller details, finally showing atoms. Another scene shows a breath- takingly real, gigantic cat flea that in reality is not bigger than one millimetre. Others show stunning high-precision images of even smaller insects, bacteria, viruses, and molecules. National Geographic commissioned the film. © Basel University Biozentrum, N. Goldie, C-CINA, Kenneth Martin Oeggerli, supported by To create the pictures, the National Geographic A high-precision image of a cat flea that in reality is not bigger than one millimetre. team initially approached the accomplished Swiss artist Martin Oeggerli, “International 14,000 images and the “micronaut”, as the artist worldwide unique combination of artistic skills, Photographer of the Year” in 2011 (International calls himself, normally needs up to 40 hours to electron microscopy and computer software to Photography Awards). add colour to one single picture. Refining the visualise new stories and scientific findings,” But even for him the project was a challenge. whole movie would be a lifelong task. says Stahlberg. The team now wants to apply He approached Stahlberg’s laboratory, which Based on a few hand-coloured pictures, a their movie technology to biological research had the facility to host a one-tonne electron group of mathematicians and software engineers topics to help make science more understandable microscope needed to deliver the high-precision from the University of Basel developed a software to the general public. pictures. Colour had to be added electronically to tool that transfers colours from one picture to the the black and white pictures, a part that Oeggerli next one, eventually adding colour to the entire http://movies.nationalgeographic.com/movies/ took care of. A five-minute-film contains roughly movie sequence. “Now we are ready to use this mysteries-of-the-unseen-world/photos/ The EMBO Journal Cover Contest is back Celebrating its 10th anniversary in 2014, this annual competition is organized by the editors of The EMBO Journal to select the best images for the front cover of the journal. Visit the website at covercontest.embo.org to find out how you can submit your pictures.

Deadline 20 December 2013

LEFT | Best Cover Image 2012: Portrait of a file clam by Eric Röttinger RIGHT | Best Cover Image 2012: Superhydrophobic swimming beauty by Martin Oeggerli ©E. Röttinger ©M. Oeggerli

©2013 EMBO EMBOencounters | Autumn 2013 | [email protected] 21 events – A GOOD READ – research opportunities Events Research opportunities embo members Alzheimer’s disease in Down syndrome: from molecules to cognition is the title of a meet- University of Oxford ing co-organized by EMBO Member Victor Tybulewicz at the Wellcome Trust Genome Weatherall Institute of Molecular Medicine, University of Oxford, is inviting Campus, United Kingdom, from 27 – 29 March 2014. Information & registration: expressions of interest for the prestigious Chair of Molecular Medicine. Please https://registration.hinxton.wellcome.ac.uk/display_info.asp?id=378 contact Professor Douglas Higgs at [email protected] for further information. EMBO Member Harald von Boehmer is one of the organizers of the Midwinter Conference 2014 at the Olympic Congress Center in Seefeld, Austria, from 18 – 23 January 2014. Institut Curie Conference homepage: www.seefeld.com/midwinter The Department of Cell Biology at the Institut Curie in Paris is offering Group Leader positions to “outstanding individuals interested in basic aspects of cell and tissue EMBO Members Giulio Superti-Furga and Denise Barlow are co-organising the Austria biology and in the mechanisms that govern normal and pathological cell EMBanniversary conference on 7– 8 July 2014 in Aula der Wissenschaften in Vienna, function.” Full details at http://umr144.curie.fr Austria. The conference celebrates 50 years of EMBO and 40 years of EMBL. Full details at: www.cemm.oeaw.ac.at/index.php?id=6 A good read – Publications from the EMBO Community embo members, Young Investigators & Fellows The microcephaly protein Asp regulates Transcriptome and genome sequencing Lineage-specific laminar organization of Dual mode operation of neuronal neuroepithelium morphogenesis by uncovers functional variation in humans cortical GABAergic interneurons networks involved in left-right controlling the spatial distribution of Marc R Friedländer (EMBO Fellow) Nathalie Dehorter (EMBO Fellow), alternation myosin-II and colleagues Oscar Marín (EMBO Young Investigator) Julien Bouvier (EMBO Fellow) Maria A. Rujano (EMBO Fellow) Nature | 15 September 2013 and colleagues and colleagues and colleagues doi:10.1038/nature12531 Nature Neuroscience | 11 August 2013 Nature | 30 June 2013 Nature Cell Biology | 6 October 2013 doi:10.1038/nn.3485 doi:10.1038/nature12286 doi: 10.1038/ncb2858 Telomeric RNA-DNA hybrids affect telomere-length dynamics and Dimeric WH2 domains in Vibrio VopF Recalibrating Equus evolution using the Kinetic framework of spindle assembly senescence promote actin filament barbed-end genome sequence of an early Middle checkpoint signaling Sarah Luke-Glaser (EMBO Fellow) uncapping and assisted elongation Pleistocene horse Daniel W. Gerlich and colleagues Jozsef Orban (EMBO Short-Term Fellow) Matteo Fumagalli (EMBO Fellow) (EMBO Young Investigator) and colleagues Nature Structural & Molecular Biology and colleagues and colleagues Nature Cell Biology | 6 October 2013 8 September 2013 | doi:10.1038/nsmb.2662 Nature Structural & Molecular Biology Nature | 26 June 2013 doi:10.1038/ncb2842 4 August 2013 | doi:10.1038/nsmb.2639 doi:10.1038/nature12323 The microprocessor controls the activity Live visualization of chromatin dynamics of mammalian retrotransposons Noncoding RNAs prevent spreading of a The species and organisms resources for with fluorescent TALEs Sara Macias (EMBO Fellow) and colleagues repressive histone mark fast and accurate identification of taxo- Yusuke Miyanari (EMBO Fellow), Nature Structural & Molecular Biology Marc Bühler (EMBO Young Investigator) nomic names in text Maria-Elena Torres-Padilla 1 September 2013 | doi:10.1038/nsmb.2658 and colleagues Evangelos Pafilis (EMBO Short-Term Fellow) (EMBO Young Investigator) and colleagues Nature Structural & Molecular Biology and colleagues Epigenetic and transcriptional signatures Nature Structural & Molecular Biology 21 July 2013 | doi:10.1038/nsmb.2619 PLoS ONE | 18 June 2013 6 October 2013 | doi:10.1038/nsmb.2680 of stable versus plastic differentiation of doi:10.1371/journal.pone.0065390 proinflammatory gd T cell subsets A two-step mechanism for epigenetic Equalization of odor representations by a Bruno Silva-Santos specification of centromere identity and Atomic-resolution monitoring of protein network of electrically coupled inhibitory (EMBO Young Investigator) and colleagues function maturation in live human cells by NMR interneurons Nature Immunology | 1 September 2013 Daniele Fachinetti (EMBO Fellow), Lucia Banci (EMBO Member) and colleagues Thomas Frank (EMBO Fellow) and 10.1038/ni.2702 Lars Jansen (EMBO Installation Grantee) Nature Chemical Biology | 3 March 2013 colleagues and colleagues doi: 10.1038/nchembio.1202 Molecular basis of tubulin transport Nature Neuroscience | 29 September 2013 Nature Cell Biology | 21 July 2013 doi:10.1038/nn.3528 within the cilium by IFT74 and IFT81 doi:10.1038/ncb2805 Structural basis of tubulin tyrosination by Esben Lorentzen (EMBO Young Investigator), tubulin tyrosine ligase Temperature triggers immune evasion by Erich Nigg (EMBO Member) and colleagues The CRAPome: a contaminant repository Michel O. Steinmetz (EMBO Member) and Neisseria meningitides Science | 30 August 2013 for affinity purification–mass spectro colleagues Elisabeth Kugelberg (EMBO Fellow) doi:10.1126/science.1240985 metry data Journal of Cell Biology | 28 January 2013 and colleagues Giulio Superti-Furga, (EMBO Member), doi:10.1083/jcb.201211017 Cerebral organoids model human brain Nature | 25 September 2013 Ruedi Aebersold (EMBO Member), development and microcephaly doi: 10.1038/nature12616 Jacques Colinge (EMBO Fellow), Madeline A. Lancaster (EMBO Fellow), Keiryn L Bennett (EMBO Fellow) Directional tissue migration through a Josef M. Penninger (EMBO Member), and colleagues self-generated chemokine gradient Juergen A. Knoblich (EMBO Member) Nature Methods | 7 July 2013 Anton Khmelinskii (EMBO Fellow) and colleagues doi:10.1038/nmeth.2557 VIDEO and colleagues Nature | 28 August 2013 Nature | 25 September 2013 doi:10.1038/nature12517 doi: 10.1038/nature12635 A reversible gene trap collection empow- VIDEO Cycles in spatial and temporal chro- ers haploid genetics in human cells mosomal organization driven by the Manuele Rebsamen (EMBO Fellow), circadian clock Giulio Superti-Furga (EMBO Member) Lorena Aguilar-Arnal (EMBO Fellow), Nature Methods | 25 August 2013 Paolo Sassone-Corsi (EMBO Member) doi:10.1038/nmeth.2609 and colleagues XMAP215 activity sets spindle length Nature Structural & Molecular Biology Women in Science 22 September 2013 | doi:10.1038/nsmb.2667 by controlling the total mass of spindle microtubules As many women as men Arabidopsis meiotic crossover hot spots Jonathon Howard (EMBO Member), study towards PhDs in the life overlap with H2A.Z nucleosomes at gene Anthony A. Hyman (EMBO Member), The EMBO Meeting – sciences. However, there are promoters Per O. Widlund (EMBO Fellow) How to survive a PhD still noticeably less women in Kyuha Choi (EMBO Fellow) and colleagues and colleagues A PhD can be a very rewarding senior positions in academic Nature Genetics | 22 September 2013 Nature Cell Biology | 25 August 2013 but also daunting undertaking. doi:10.1038/ng.2766 doi:10.1038/ncb2834 scientific research. Why is We have asked participants at this and what can be done? Reproducibility of high-throughput The N-terminal acetylation of Sir3 stabi- the PhD meets Postdoc Party mRNA and small RNA sequencing across lizes its binding to the nucleosome core We asked several high-profile laboratories particle at The EMBO Meeting 2013 for scientists, including Kai Simons Marc R Friedländer (EMBO Fellow) Fabrizio Martino (EMBO Fellow), their advice on how best to and Susan Gasser at The EMBO and colleagues Daniela Rhodes (EMBO Member) survive a PhD. Meeting 2013 in Amsterdam. Nature Biotechnology | 15 September 2013 and colleagues http://youtu.be/PBBQ2blTQP4 http://youtu.be/iUZqZ8aIzHk doi:10.1038/nbt.2702 Nature Structural & Molecular Biology 11 August 2013 | doi:10.1038/nsmb.2641

EMBO Scientific Publications Awards of excellence Poster Prize winners EMBO Members 2013 Nobel Prizes Israel Prize King George IV in 1825, are an annual Congratulations to the following EMBO Associate Members Randy W. Nathan Nelson of the Tel Aviv award recognising important contri- winners: Schekman and James E. Rothman University has been awarded the butions made in the fields of physical, won the 2013 Nobel Prize in Israel Prize in the field of Life Sciences biological and applied sciences. Physiology or Medicine jointly with for the years 2012 – 2013. The Israel The EMBO Journal US National Academy of Sciences Thomas C. Südhof for their discoveries Prize is an award handed out by the Andrew Kodani of machinery regulating vesicle traffic, State of Israel and is largely regarded Edward De Robertis of the University University of California, San Francisco, USA a major transport system in our cells. as the state’s highest honour. Nelson of California, Los Angeles, was elected is an expert in biochemistry and to the National Academy of Sciences Centriolar satellites localize microcephaly proteins EMBO Member Michael Levitt was molecular biology, with an interna- in recognition of his distinguished to the centrosome to control centriole duplication the winner of the Nobel Prize in tional reputation in basic research and continuing achievements in basic Chemistry jointly with Martin Karplus Presented at The EMBO Meeting into cell membrane molecular research. and Arieh Warshel for the development Amsterdam, The Netherlands | 21 – 24 September 2013 proteins and complexes. of multiscale models for complex Human Genome Organization Vladislava Chalei chemical systems. American Society for Microbiology Council University of Oxford, UK Lifetime Achievement Award 2013 International Balzan Prize Karen B. Avraham of the Tel Aviv DALI, a novel chromatin-associated lincRNA involved Julian Davies from the University University, Israel, and Huanming Yang in controlling gene expression in neuronal cells Pascale Cossart of the Institute of British Columbia, Canada, was of the Beijing Genomics Institute in Pasteur in Paris is one of the winners Presented at the EMBO | EMBL Symposia: awarded the 2013 American Society China, were elected to the Human of the 2013 International Balzan for Microbiology Lifetime Achievement Genome Organization (HUGO) Council The Non-Coding Genome Prize, worth 750,000 Swiss francs, for Heidelberg, Germany | 9 – 12 October 2013 Award. He was recognized for his this year for the term 2013-2015. her work on the molecular biology pioneering work on antimicrobials of pathogenic bacteria and their Quentin Defenouillere and his leadership in the field of Bernhard Rensch Lecture interaction with host cells. Speaking Institut Pasteur, Paris, France microbiology. Sarah Teichmann of the European for the Balzan Foundation, Peter Suter, Bioinformatics Institute and Wellcome A Cdc-48-associated complex bound to 60S particles honorary vice president of the Swiss German National Academy of Trust Sanger Institute Cambridge, is required for the clearance of aberrant translation Academy of Medical Sciences, said, Sciences United Kingdom, gave the Bernhard- products “Her research has provided very signifi- Jörg Vogel of the University of Rensch-Lecture in Evolutionary cant insights into the mechanisms Presented at the EMBO Conference: Eukaryotic Würzburg, Germany, has been elected Biology at the University of Münster, underlying infectious diseases and RNA turnover: From structural insights to diseases to Leopoldina, the German National Germany, in June 2013. how they might be combatted.” Strasbourg, France | 21 – 24 April 2013 Academy of Sciences, and the American Academy of Microbiology European Research Council (ERC) EMBO Reports Max Rössler Prize this year. Starting & Advanced Grants The 2013 Rössler Prize has been A. Kathrin Müller-Rischart Five EMBO Young Investigators and awarded to Olivier Voinnet, Professor Ludwig Maximilians University Munich, Germany Buchanan Medal Installation Grantees have received of RNA Biology in the Department of Douglas Higgs, head of the MRC 2013 ERC Starting Grants: Ebru Erbay, The E3 ligase Parkin regulates a novel stress- Biology, ETH Zurich. Voinnet receives Weatherall Institute of Molecular Reto Gassmann, David Keays, Fyodor protective pathway linking NF-kappaB signaling and the 200,000 Swiss franc research prize Medicine at Oxford University, has Kondrashov and Melina Schuh. mitochondrial integrity via linear ubiquitination for his groundbreaking discoveries in been named winner of the Buchanan For the full list of EMBO Members Presented at The EMBO Meeting the field of molecular and cell biology. Medal by the Royal Society. He who received the 2013 ERC Advanced Amsterdam, The Netherlands | 21 – 24 September 2013 2013 EMET Prize received this medal for his outstand- Grants please go to: http://erc.europa. ing work on the regulation of the Isabel López de Silanes eu/sites/default/files/document/file/ Ben-Zion Shilo of the Weizmann human alpha-globin gene cluster and Spanish National Cancer Center, Madrid, Spain erc_2013_adg_results_ls.pdf Institute of Science and Giora the role of the ATRX protein in genetic Identification of the subtelomeric sequence of Simchen of the Hebrew University of disease. The Buchanan Medal is EMBO STAFF the long non-coding RNA TERRA unveils its role at Jerusalem, Israel, received the 2013 awarded biennially for contributions telomeres EMET Prize in Genetics. The EMET to the medical sciences. SPARC Innovator Award Prize is an annual prize given for Presented at the EMBO | EMBL Symposium: The July 2013 SPARC Innovator Award excellence in academic and profes- The Non-Coding Genome Royal Medal recognizes creators of the San sional achievements that have far Heidelberg, Germany | 9 – 12 October 2013 Sir Walter Bodmer was one of three Francisco Declaration on Research reaching influence and significant recipients of this year’s Royal Medals Assessment (DORA). The list of award- contribution to society. The award is Molecular Systems Biology from the Royal Society, in recogni- ees includes Bernd Pulverer, Head of sponsored by the A.M.N. Foundation tion of his seminal contributions to Scientific Publications at EMBO. The Nicolas Battich and Thomas Stöger for the Advancement of Science, Art population genetics, gene mapping prize is awarded by the US-based University of Zurich, Switzerland and Culture in Israel in cooperation and understanding familial genetic Scholarly Publishing and Academic with the Prime Minister of Israel. Large-scale image-based transcriptomics in disease. The Royal Medals, founded by Resources Coalition. thousands of single human cells at single-molecule resolution EMBO YOUNG INVESTIGATORS Presented at The EMBO Meeting Erik K. Fernström Prize Royal Society Francis Crick Lecture 2014 Colworth Medal Amsterdam, The Netherlands | 21 – 24 September 2013 Tibor Harkany, Professor of The Royal Wellcome Trust Sanger M. Madan Babu, MRC Laboratory of EMBO Molecular Medicine Neurobiology at Karolinska Institutet, Institute Associate Faculty member, Molecular Biology in Cambridge, has Sweden, has been awarded the 2013 Duncan Odom, has been invited been awarded the 2014 Colworth Aurélie Ladang Erik K. Fernström Prize for “important by the Royal Society to deliver the Medal by the Biochemical Society in University of Liege, France results that contribute to an in-depth prestigious Francis Crick Lecture in recognition of his expertise in bioinfor- Tumor initiation in the intestine requires the understanding of the principles that 2014. The lecture is awarded each matics analysis of protein structure elongator acetylase complex control structure and function in year to celebrate a biological sciences and gene networks. The medal is nerve cells.” researcher, generally working in the awarded annually to a biochemist Presented at The EMBO Meeting field of genetics, at an early stage in under the age of 35 for outstanding Amsterdam, The Netherlands | 21 – 24 September 2013 their career. research achievement. Appointments embo members Suzanne Cory, professor at the Jan-Michael Peters has been appoint- As of September 2013, Geneviève Editorial University of Melbourne, is the first ed Scientific Director of the Research Almouzni is director of the Institute woman elected as President of the Institute of Molecular Pathology (IMP) Curie Research Centre. The specialist Australian Academy of Science. She in Vienna, effective 1 July 2013. The in epigenetics is the first woman Managing Editor Barry Whyte was also the first woman to be German cell biologist has been leading since Irène Joliot-Curie to take over the Editor Yvonne Kaul Director of the Walter and Eliza a research group at the IMP since 1996. management of the Institute Curie’s Print layout Uta Mackensen Hall Institute of Medical Research He took over the position from Barry research activities. (1996 – 2009). Her research has had a Dickson who is leaving for Janelia Web version Aditya Kusuma Jati major impact on the understanding Farm Research Campus in the United E-newsletter Sandra Krahl, Katja Linssen of immunology and the development States. of cancer.

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