Detlef Weigel the EMBO Meeting 2015 Making the Killer Mosquitoes

Home , Aziz Sancar, Detlef Weigel, Frank Uhlmann, Laurence Hurst, Liam Dolan, Li Jiayang

AUTUMN 2015

ISSUE 31

Emerging Biotechnologies Making the killer mosquitoes kill themselves PAGE 7

Interview The EMBO Detlef Meeting 2015 Weigel PAGES 4 – 5 PAGE 3 E xploring in Q uotas A cademia

Focus on Women in Science News iBG-izmir: the largest public In perspective Short history of the EMBO Laboratory Management Course research investment in the history of “Arolla workshops” – a series of for Female Leaders in Science and new Turkey – with strong EMBO ties EMBO workshops held since 1972 report on gender quotas in academia

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www.embo.org FOCUS ON WOMEN IN SCIENCE

How to become an accomplished lab leader Third EMBO Laboratory Management Course for Female Leaders in Science

Some take-home messages: ©EMBL photolab | Marietta Schupp ➔ Awareness is the frst step toward change MBO has offered more than 100 Laboratory confident way, how to deal with superiors and Management Courses since their launch in how to reach the people in the lab,” comments ➔ Know your values and strengths and be E2005. The courses are designed for post- co-trainer Damjana Kastelic, who is also a scien- clear in what you want doctoral researchers and group leaders. The one tist at the German Cancer Research Center. ➔ Understand what you can infuence (and that took place in mid-October near Heidelberg The course started with exercises on disman- what not) – either personally or at work addressed a more specific audience. Only female tling stereotypes and contrasting them with real- scientists were targeted this time. It was the ity. This module was followed by a discussion ➔ Be aware of hidden biases third Laboratory Management Course for Female about the existence of hidden biases, to which ➔ Personality often explains behaviour Leaders in Science since 2013. 16 participants both men and women are likely to succumb. better than gender does “Such topics could and should also be discussed in a mixed gender group. It is a different experi- ➔ Be confdent in your communication ence though to discuss them with women only,” and decision-making “One of the things I implemented outlines Janssens. ➔ There are different leadership styles – A session on strengthening self-confidence immediately after coming back develop your own from the course was that I started followed on the second day. Dealing with guilt, with rejection or with a negative behaviour were to prepare myself better for group on the agenda. One of the exercises involved and one-on-one meetings with a role-play on active listening, which aims at understanding the different layers of a conflict. Women remain under-represented in posi- individual team members,” says “Scientists are used to focus on solutions,” says tions of scientific leadership – even though they Jacqueline Jacobs, group leader at Janssens who worked as a researcher for 19 years. make up a majority of PhD graduates in scien- Yet in a conflict situation, a lab leader needs to tific disciplines – for a variety of reasons. Lack the Netherlands Cancer Institute, take a step back and give some thought to what is of self-confidence and the fear of not being able who attended the very first course really being said. The examples discussed during to combine family with a career in academia are in 2013. “I am now better at that exercise were actual situations taken from the main hurdles. “There are still big inequali- day-to-day lab life. ties when it comes to gender in career progres- making clear what I expect from The morning session on day three of the course sion. We all know that. Providing secure and people in such meetings.” focused on developing an individual leadership quality childcare and proper mentoring is crucial style. A lot of attention was put on body language, to change this,” says course participant Renata confident voice and positive language. The train- Basto who is also a member of the EMBO Young ers encouraged the participants for example to Investigator network. The Portuguese scientist came to Heidelberg for this three-day-session rephrase answers so that they sounded confi- leads a laboratory of eight young researchers at from all over Europe – with various expectations. dent and convincing. At the end of the exercise, the Institute Curie in Paris, France. Her goal was “Self-confidence, conflict management and attendees were asked to present themselves. The to learn more about improving work-life balance, communication in general were the central topics,” emphasis on non-verbal communication was new dealing with guilt, time management and differ- says Hilde Janssens, who ran the course for the to this course and specifically requested. “It was ent leadership techniques. “I wish I had done this third time now. “The most frequently asked ques- not such a burning topic in previous courses,” course earlier,” she says. tions were how to get your message across in a recalls Janssens.

The report, published in September, looks Exploring quotas at the potential benefits and challenges that could arise from the use of quotas as one way in academia to achieve better gender balance in academia. It describes options for introducing quotas and Gender quotas are one tool that provides information for decision makers who could improve gender balance at the might consider implementing them. The year-long study involved interviews with highest levels of academia. Their a wide range of stakeholders followed by a closed use is controversial. workshop in Berlin, where options for the use of gender quotas were analyzed. The working group e it on scientific boards, on hiring commit- included gender researchers, heads of research tees, or at the top of hierarchies in univer- institutes, funders and scientists (see also Bsities and other research organizations: interview with Detlef Weigel below). The group women are still under-represented. The overall discussed measures such as cascade models for numbers and ratios of women to men in senior hiring, quotas for the composition of committees, academic positions are much smaller than would and equal success rates in funding schemes. be expected given the number of female univer- Exploring sity graduates in the last decades. The full report is available at quotas One tool that could diminish disparities in www.embo.org/documents/science_policy/ in academia the number of women and men in academia exploring_quotas.pdf Gerlind Wallon, Sandra Bendiscioli, is the use of gender quotas. Exploring quotas and Michele S. Garfnkel, EMBO in academia is the report of a study conducted by EMBO in collaboration with and funded by the Robert Bosch Stiftung. Sandra Bendiscioli, Michele Garfinkel and Gerlind Wallon from EMBO are the authors of the final report.

interviewing a wide range of people in executive positions who had direct experience with quotas. The numbers I particularly appreciated the workshop that they organized together with Ingrid Wünning Tschol from the Bosch Foundation, to help identify best speak for practices in implementing quotas. One of the greatest challenges is that hiring or funding deci- themselves sions are generally made at such a ﬁne-grained level that bias, be it conscious or not, is difﬁcult Interview with DETLEF WEIGEL, to detect. The report describes a series of possible Chair of EMBO Council for solutions to this issue.

2013 – 2015 and Director at In your various leadership roles as scientist, the Max Planck Institute for director at the Max Planck Institute and Chair Developmental Biology in of EMBO Council, what do you think about using quotas? Tübingen, on the representation Although I thought that I was already quite well of women in academia and his informed, the workshop drove home the point that quotas are not only an appropriate, but ©Max Planck Institute role in the EMBO-led study. also in my view essential tool to accelerate the pace with which women are hired in academic leadership positions. That progress has been too You were one of the motivators of the gender quite a few conferences over the years, and I had modest so far has many reasons, one being that quota study. Where did the idea come from? noticed that male names surfaced much quick- performance criteria are often skewed and do not Like many others, I was initially sceptical about er than female names when my colleagues and take the entire breadth of academic work, such as quotas, not least because of the concern that I started to think of potential speakers. Once I departmental responsibilities, teaching, mentor- women would be branded as “quota candidates”, had identified this as a problem and made it a ing and supervision, properly into account. whose success was not merely due to their scien- personal rule not to be satisfied with an unbal- Finally, I do not accept the excuse that “academia tific achievements. However, it was clear that the anced list of speakers, I was surprised how easy is simply different” and that quotas are therefore Max Planck Institute and other organizations it was to come up with lists where half or more not workable. Large corporations and parliaments were increasing the number of women in leader- were women, without any compromise in quality. can do it, and we should be up to the task as well. ship positions too slowly, and that new measures After all, as scientists we often pride ourselves were required to change this situation. While it What did you think about the process and the in being in the avant-garde. This is certainly one is rare these days to encounter blatant discrimi- methodology used in the project? area where we have not always shown such lead- nation, the numbers speak for themselves. I had I was very impressed by the systematic approach ership. And as it turns out, I learned from the already come to the conclusion that formal rules that Michele, Sandra and Gerlind took. They workshop that the concerns about the “quota” can be a powerful tool to redress the current started with a literature meta-analysis, and updat- perception are largely unjustified. imbalances. For example, I have been organizing ed the conclusions with lessons learned from

©2015 EMBO EMBOencounters | Autumn 2015 | [email protected] 3 Geneviève Almouzni of the Institute Curie Joan Steitz of Yale University School of gave a plenary lecture in the session on Medicine and the Howard Hughes Medical nuclear architecture. She commented: Institute gave an opening lecture on the “Speaking at The EMBO Meeting is a molecular events involved in the formation fantastic opportunity to present research of messenger RNA to the wider scientifc community.”

Sarah Teichmann and Ido Amit received the EMBO Gold Medal at the opening session of the meeting. “Informatics has always been at the heart of my research, using statistics and computer science to tease out meaning from the ‘wet-lab’ experiments we carry out,” said Teichmann. Ido Amit has received the award for his work to reveal the function of the immune system. He commented: “It is a wonderful feeling that prominent scientists believe we are on the right way, but also a huge responsibility to continue and make progress towards our research vision.” T he EMBO Meeting 2015

4 EMBOencounters | Autumn 2015 | [email protected] ©2015 EMBO enzyme adipose triglyceride lipase (ATGL) and its On excellence, serendipity and protein co-activator CGI-58 facilitate lipid catabolism in both mice and humans. He also spoke Rosetta’s comet rendezvous about lipolysis in cancer and cancer-associated cachexia – an uncontrolled and irreversible loss Highlights from The EMBO Meeting 2015 of weight in cancer patients. In the Science Policy session on Excellence and inclusion in evaluating research Jack Stilgoe of University College London and Claudio Sunkel, osted in Birmingham this time, The The challenge of being an explorer was also professor at the University of Porto, discussed EMBO Meeting featured talks from more in the centre of Matt Taylor’s special lecture on what scientific excellence really means, what type Hthan 80 life scientists speaking at 20 The ESA Rosetta mission. Taylor, project scien- of science could be funded by governments and concurrent sessions and three sets of plenary tist at the European Space Agency (ESA), gave how investments into Research & Development lectures. Conference chairs Gillian Griffiths, an enthusiastic talk summarising the journey of translate into the economic success of a country. Geneviève Almouzni and Jürgen Knoblich struc- Philae to comet 67P/Churyumov-Gerasimenko. tured the themes of the concurrent sessions into Launched in 2004, the mission has been coor- five groups: cytoplasm, medicine, membrane, dinated by hundreds of people. “I am a small, nucleus, and signalling. very tiny piece of the machine,” said the British Joan Steitz’ talk on Nuclear non-coding RNAs physicist. In November 2014, Rosetta success- of viral and cellular origin inaugurated the four- fully deployed Philae to the surface of the comet: day conference full of high-quality scientific pres- “From 23 km away from the comet, we dropped entations, networking events and career develop- the lander.” The awareness of the mission ment sessions. “She is a fantastic role model and amongst the general public reached a spectacular she inspired me by showing that you can have a 80 per cent in some European countries at that family and do great science,” said Gillian Griffiths time. in her introduction to Joan Steitz’ keynote lecture Both Louis-Jeantet Prize lectures took place on on the opening evening. Monday, day three of the conference. Emmanuelle Keynote lecturer Peter Walter from the Charpentier gave a glimpse into the origins, University of California, San Francisco, talked on mechanisms and applications of the CRISPR-Cas9 Monday morning about The serendipitous path technology. Rudolf Zechner explained the mecha- of discovery: from protein folding to cognition nisms governing the metabolism of lipids. He

on Monday morning. He explained how a small showed in his lecture that the recently discovered ©European Space Agency drug-like compound called Matt Taylor ISRIB renders cells insensi- tive to translational inhibition. The properties of this compound are truly remarkable: ISRIB proved to be a cognitive enhancer in rodents, signiﬁcantly improving their long-term memory. “Looking back at my career I can say that the path of discovery is neither linear nor predictable,” said Walter. His work on the unfolded protein response (UPR) provides a wonderful example of how serendipity can shape scientiﬁc discovery: The molecular machines that transmit information about defective protein folding and regulate appropriate gene expression programmes function in unusual, unprecedented ways. ©Images: Martyn Hicks

high-tech product development, and high quality Izmir Biomedicine and Genome services for both public and private sectors. The centre has already attracted a number Center – a model for the region of young talents from around the world. Nearly twenty of the planned 32 independent basic and Largest public research investment in the history of Turkey – translational research groups have been formed with strong EMBO ties and are already working in the institute. Two of them are headed by EMBO Installation Grantees, Günes Özhan and Gerhard Wingender. The urkey is an emerging country that has hub for biomedical research, innovation, service groups are organized as multidisciplinary clusters accelerated its investment in science and and education in the Eastern Mediterranean connecting researchers and clinicians – a struc- Ttechnology over the last decades. Between Region. Located between the Middle East, ture that is unique for the Turkish research land- 1980 and 2015 the number of Turkish universi- Western Asia and Europe, it is predestined to scape. They cover focus areas such as targeted ties increased almost tenfold, reaching 180. Life function as a cultural bridge, where scientists can molecular therapy, stem cell and gene therapy, science research in Turkey is conducted mainly at meet and cooperate. “We designed the institute immunotherapy, and genomics of rare diseases. state universities. An important alternative to the as a model for the entire region,” says Öztürk. Their research is supported by state-of-the-art public higher education institutions are foundation universities, typically set up by wealthy businessmen. Large basic research institutes are on the rise – yet at a slow pace. In relation to its gross domestic product, Turkey still spends less than half as much on research as the EU average. The dream of creating a large-scale, inter- nationally competitive life science institute in Turkey was born many years ago, but only realized when the Izmir Biomedicine and Genome Center (iBG-izmir) was created. Located on the campus of Dokuz Eylül University in Izmir – Turkey’s third largest city – the iBG-izmir was launched in September. The institute is the largest public research investment in the history of the Republic of Turkey. The opening ceremony was attended by the Turkish Minister of Science and other government repre- sentatives. It also featured a series of scientific presentations including a With a size of more than 20,000 square talk from Nobel Laureate Tim Hunt. meters, the centre is designed to host In his speech he said that the creation 32 research groups and educate 150 of the institute is a “fantastic opportu- graduate students nity” for talented Turkish scientists to ©iBG-Izmir return to their country. “Both EMBO and EMBL played important roles “Time will tell whether our idea gains ground.” core facilities for biobanking, in vivo and in vitro in shaping the path to the creation of the insti- The director’s close association with EMBO imaging, genomics and bioinformatics, and a tute,” said Mehmet Öztürk, founding director and and INSERM in France allowed him to estab- vivarium for rodent, zebra fish, and fly animal its driving force. Maria Leptin, EMBO Director, lish strong ties with European institutes and life models, to name just a few. and Iain Mattai, EMBL Director General, current- science researchers and to facilitate the institute’s Turkey is now trying to lure its talented natives ly serve on the Scientific Advisory Committee European integration. His association with The back home – as well as to attract foreign scientists. of iBG-izmir. Öztürk, who was elected EMBO World Academy of Sciences (TWAS), an academy TÜBITAK has developed several programmes to Member in 1994, consulted EMBO and EMBL working for the advancement of science in devel- increase the mobility of researchers within the directors over the years, seeking advice on how to oping countries, offered him insights into the Horizon 2020 framework. The EMBO Installation plan and structure the emerging institute. “EMBO specific problems of emerging countries. Grants are also financed by TÜBITAK – in collab- has been following the development of science Currently, the major funding of iBG-izmir oration with EMBO. The iBG-izmir has already in Turkey since 1993, when the country joined comes from Dokuz Eylül University, the Ministry attracted a number of young scientists through the EMBC, the funding body of EMBO,” said of Development and TÜBITAK, the Scientific these programmes. Now, the centre is looking to Deputy Director Gerlind Wallon in her speech and Technological Research Council of Turkey. recruit specialists in genomics and bioinformatics. at the opening ceremony. To date, twenty scien- The iBG-izmir is candidate for a centre of excel- tists in Turkey have been supported by EMBO lence, recognized by the Ministry of Development www.ibgizmir.deu.edu.tr Installation Grants, created to attract scientists to of Turkey – a status that will secure funding. set up their independent laboratories in partici- In the next few months, the government will pating member states. make a decision on which centres to fund; the iBG-izmir, designed as a multidisciplinary clus- iBG is considered a strong candidate. The insti- ter, is striving to become a national and regional tute is expected to strongly focus on innovation,

before they can reproduce and before they can become transmitters of disease, reducing the population in successive generations. There is currently no vaccine available or any speciﬁc medication for Dengue. So the only effective way to control the disease is to control the mosquito that spreads it. The Oxitec solution is far and away the most environmentally sustainable way to control Aedes aegypti since it affects only the target species and the insects and their genes do not persist in the environment.

Dengue fever is common in more than a hundred countries. Why did you choose the US for feld trials? It is true that the infection is found predominantly in the tropics and subtropics, but this is an inva- sive mosquito that keeps spreading, and it has become even more prevalent in the US. The last outbreak of Dengue in Florida was around 2009. That mosquito is still there. After that outbreak, the Florida authorities asked Oxitec if they could trial our mosquito.

How successful were the trials you ran in Panama, Cayman and Brazil? Making the killer In every trial, the dengue mosquito, Aedes aegypti, was reduced by more than 90% – this is an mosquitoes kill unprecedented level of control by any method. Results have been independently peer-reviewed themselves and published in the scientific literature, including most recently studies in Brazil and Panama. The national biosafety group in Brazil has now approved our mosquito for release throughout Parasitic diseases have been the centre of the entire country. attention of this year’s Nobel Committee: ©Oxitec Were you surprised by the opposition of the William Campbell and Satoshi Õmura locals in Key West and now in the Florida Keys? have been recognized for their discovery of the drug avermectin Not really. Advancements in science and technology generate some debate, especially when they and its derivative ivermectin. Youyou Tu from China received the are first being implemented. There are a lot of Nobel Prize for her discovery that artemisinin is highly effective questions about risks and benefits. So it is impor- against the malaria parasite. Next to the traditional, drug-based tant to engage communities directly and also look to the data on diversity of opinions to better therapies to combat parasitic disease, promising biotechnologies understand people’s views. There have been a have recently been launched – an emerging one was on the agenda series of independent surveys that show that the of the 2015 EMBO | EMBL Science and Society Conference. One local population is in fact neutral or supportive of genetically engineered mosquito control. We of the conference speakers was SIMON WARNER, Chief Scientific have arranged a number of town-hall meetings Officer of Oxitec, a British biotechnology company. Oxitec produces and public engagement sessions so people can genetically engineered Aedes aegypti mosquitoes to fight Dengue and come to voice their opinions and meet our scientists face to face to get their questions answered. Chikungunya – viral diseases that have no cure and are spreading This dialogue is an important part of the process. around the world. In an interview, Warner explains Oxitec’s approach and speaks about the reaction of the residents to local field trials. www.oxitec.com

The EMBO Science Policy Programme You are planning to release several millions of years now, and if and when FDA says this project is involved in European discussions about genetically altered Aedes aegypti mosquitoes in can go ahead, FKMCD will run the trial – with responsible research and innovation the Florida Keys. What is the status quo? technical support from Oxitec. to ensure that research, for example in Pesticides can only reduce this mosquito by up biotechnology applications, is conducted to ﬁfty percent at best. That leaves too many What is the Oxitec approach? responsibly and for the beneft of society mosquitoes to pick up and spread painful diseas- We develop male mosquitoes with a self-limiting and of the scientifc community. es like Dengue, Chikungunya and Zika virus. gene so after they mate with the pest female Aedes See www.embo.org/science-policy/ We have been working with the Florida Keys aegypti mosquitoes, their offspring die before biotechnology-and-genomic-technologies Mosquito Control District (FKMCD) for several reaching adulthood. This way the offspring die

the Cancer Genome Atlas (TCGA). They have New biobank for brain tumour also shown that the cell lines essentially retain the same features as the cells in the original research tumour. The associated database is searchable and contains all available information about the EMBO Member BENGT WESTERMARK and colleagues at Uppsala University cells, e.g. genetic alterations, subtype and clinical have developed a biobank with cell lines that can be used as a model of data on the patients. EMBO Member René Bernards of the the incurable brain tumour type glioblastoma. Netherlands Cancer Institute is one of the early users of the biobank: “The HGCC biobank is a he purpose of the biobank is to become established cancer cell lines exist, including brain great resource because it reflects the molecular a public resource that enables accurate tumour cell lines, but for various reasons they are heterogeneity of the human glioblastoma tumour Tcell-based modelling of glioblastoma less valuable as models for the incurable brain types and offers an advantage over the classical diversity using stem cell conditions,” says Bengt tumour type glioblastoma: Some of the present serum-cultured lines. For instance, in terms of Westermark, who has worked on the resource collections have remained to a large extent gene expression, the new cell lines cluster with for the past five years. The biobank, called private and have limited distribution. The culture the major subtypes identified in human glioblas- HGCC (for Human Glioblastoma Cell Culture), is conditions of other established cell lines do not toma much better than the serum cultured lines. publicly available for researchers and all informa- allow the properties of the original cancer cell to Also, they seem to model well certain aspects tion about the cell lines can be retrieved from a be maintained. Serum-cultured cell lines do not of what we know about clinical glioblastoma database linked to the biobank. The new tool has copy the phenotype of the tumour in vivo. The progression.” been described in a paper published in the jour- major advantage of the HGCC biobank is, that The researchers behind the study hope that nal EBioMedicine in August 2015. its 48 human glioblastoma cell lines are cultured HGCC will become a well-used resource that will Human cancer cell lines – such as the famous under neural stem cell conditions. accelerate the development of more efficient ther- HeLa cells – are used for a wide variety of The HGCC panel has several advantages. The apies for patients with glioblastoma. “The value research projects, both in academia and in the cells are clinically annotated and unambigu- of this resource will increase proportionally with pharmaceutical industry. The development of ously identifiable by a unique STR profile. The its usage,” says Westermark. new cancer drugs and therapies requires experi- researchers have applied genomic- and compu- mental models that are representative of the tational analysis to assign a molecular subclass, www.hgcc.se cancer type that is studied. Currently, many according to the widely used classification from

EMBO Press Poster Prize Winners EMBO in perspective: THE EMBO JOURNAL A half century in the life sciences Iwo Kucinski Gurdon Institute, University of Cambridge, United now free to read online Kingdom Cell competition: the molecular signature of loser cells The EMBO Meeting 2015

EMBO REPORTS

Guillaume Rey University of Cambridge, United Kingdom Central carbon metabolism regulates circadian

oscillations ©EMBL PhotoLab | U. Ringeisen The EMBO Meeting 2015 Now, anyone with interest in the story of the creation of EMBO, its growth and expansion can EMBO MOLECULAR MEDICINE enjoy reading EMBO in perspective: A half-century in the life sciences online. The book is based on Myra Chavez personal interviews with Sydney Brenner, Luca Cavalli-Sforza, Georges Cohen, James Watson and the Dept. of Plastic Surgery, TU München, Germany & directors of EMBO. Its six chapters are available at www.embo.org/anniversary/book | For more FONDAP-GGR, Universidad de Chile, Santiago, Chile information on how to obtain a hard copy of the book please contact [email protected] Towards autotrophic tissue engineering: photosynthetic biomaterials for tissue regeneration CONTENT The EMBO Meeting 2015 ➔ CHAPTER 1 ➔ CHAPTER 3 ➔ CHAPTER 5 MOLECULAR SYSTEMS BIOLOGY Before the beginning Engineering success EMBO embraces the life Angelika Feldmann Molecules and microbes in the Responding to the challenge of sciences Dept. of Biochemistry, Oxford University, United Nuclear Age new technologies From the organism to the Kingdom ➔ CHAPTER 2 ➔ CHAPTER 4 molecule and back Quantitative analysis of DNA methylation turnover reveals its preferential target sites and The birth of EMBO Expansion and engagement ➔ CHAPTER 6 potential mechanisms Some creation myths and the Programmes and policies Future visions The EMBO Meeting 2015 growth of an organization within and beyond Europe A few last words

truth”, so the emphasis at Arolla was on discuss- The “Arolla Workshops” are ing results in all details. Each session began with Short History a 40-minute review of the current knowledge in a series of EMBO workshops the field to be addressed, followed by 20-minute- of the EMBO devoted to eukaryotic molecular talks describing the recent advances. Most impor- biology and genetics. The most tantly, the chairperson held a regular pre-meeting with the speakers, who would pass on the latest Workshops recent workshop took place in information. August 2015 and was organized An important feature of the meeting was that in Arolla by Susan Gasser of the Friedrich ample time was given outside the sessions for the discussion of science. The six-day-meeting A “happening” rather than a Miescher Institute in Basel. The kept afternoons free for this purpose. “Let people meeting – an EMBO workshop focus of this essay is on the feel good” was the maxim – a relief from stress history of the Arolla Workshops and tense scientific battles. There were also wild with a long tradition. Personal parties, often after wine tastings down in the memories by early participant, and the ideas behind them. valley, and moments of real grace, such as when EMBO Member Klaus Scherrer Charly Thomas played ragtime on a 19th century piano, or Mark Ptashne’s violin sounded in the hotel. Hospitality was high on the agenda. Passionate discussions took place with Francis Crick about “junk DNA” and alternative explanations, leading to the first ideas about 3D genome architecture by 1980. Mark Ptashne and Kurt Wüthrich argued about the stability of hydrogen bonds in DNA-protein interaction. On the practical side, many later biotech pioneers from compa- nies such as Biogen, Chiron, Progen and Intercell attended Arolla. For Steven McKnight, the found- er of the US biotech-company Tularik, it was “the best meeting I ever attended”. Over the years, the workshop changed with the times. At some point Arolla became a real “jet-set” meeting: participants were flown in from Japan, the US and Europe to speak about the same transcription factor. Walter Schaffner restored much of the Arolla spirit by returning to a more modest, but still high-calibre meeting. Later, some excellent meetings were devoted exclusively to development. The original idea, however, was to avoid specialisation and to break ©Klaus Scherrer routine; indeed, the best ideas spring up at cross- roads of science. In 2015, the workshop returned he series was established in 1972 with the lecture hall (and modern bathrooms) after the to broader topics thanks to Susan Gasser. help of US friends Sheldon Penman and first meeting. Arolla is not a “happening” any more; the TRobert Perry. The workshops had – and The main point of the series was (and attempt we undertook to enforce real discussion continue to have – a distinct flavour due to the remains) to focus discussion – down to hard- was possibly more than could be asked for in time original concept of the founders. Former EMBO core chemistry and physics – on results and and effort. But it has remained a particular spot Director John Tooze once praised the series as concepts that have proven to stand the test of for scientific exchange for more than forty years. “one of the best that EMBO organizes”. By 1982, time, although being largely forgotten for a while. The fact that data and concepts first discussed however, his focus on Heidelberg as the centre of Indeed, the value and validity of much of what at Arolla between 1972 – 1985 have come back EMBO activities led him to suggest it should be we discussed in those early days has only recent- to the surface today seems to legitimise the idea discontinued, despite a petition signed by more ly been confirmed by ENCODE data: for instance and style of the meetings. Rigorousness is the than 100 participants. Max Birnstiel, then Chair pervasive transcription, the prevalence of post- duty of the scientist – one that is unfortunately of EMBO Council, saved most of the concept by transcriptional regulation, the size of primary not always respected. Sadly, the pressure of the initiating a new series, which still lives on to be transcripts and 3D genome structure, etc. How “science business” today can lead to stress and held in Arolla, Switzerland, every third year and did it all begin? competition that sometimes results in corner is chaired by outstanding Swiss scientists. The initial idea for the series was sparked by cutting. To avoid this, we need to take the time John Paul, one of the first molecular haematol- a 1970 Cold Spring Harbor (CSH) symposium: for real reflection and discussion in peaceful ogists, who worked in Glasgow, once described a meeting with five-minute talks transmitted to surroundings – just like in Arolla. an early workshop as a “happening”, rather than secondary rooms by video. However, this set- a meeting. Its concept was special indeed, not up meant no real discussion was possible, so Klaus Scherrer, Institut Jacques Monod, CNRS and least the location. The Arolla village is placed in such type of meetings became a source of what Univ. Paris Diderot scenic woodland in front of three towering moun- we termed “consensus truth” or, even worse, [email protected] tains and glaciers. Just below the Alps and the “consensus methods”: the acceptance of superfi- tree-line stands the cosy Grand Hotel Kurhaus, cial scientific notions because of the reputation of which was built in the 1870s. The hotel is run by speakers and their epigones. We wanted a meet- the Weatherill-Selz family, who installed a proper ing that would deliberately avoid “consensus

with a lower number of sequenced DNA reads selected by random sub-sampling2. For simplicity, our QC system provides global QC indicators Quality control system and QC in the form of a 3-letter grade scale that ranges from AAA (highest quality datasets relative to the database for functional genomics total datasets in the QC database) to DDD (lowest quality datasets). A free tool to improve data quality and the value of results obtained As this procedure is universal and can from data mining and integration be applied to every type of Next-Generation Sequencing (NGS)-derived profile, it has been used to assess the quality of datasets available in the public domain. Currently, the NGS-QC data- ecent technological advances and cost world continue to generate functional genom- base hosts the quality descriptors for more than reductions of massive parallel sequencing, ics data. All these efforts generate impressive 26,000 public datasets, covering a great variety Rin combination with a variety of molecu- amounts of data filling up public repositories of model organisms and data types. Within short, lar biology methods, has greatly facilitated the enabling the scientific community – in princi- the database will be complemented with a qual- functional genomics. Exponentially increasing ple – to perform further exploratory and integra- ity assessment of datasets on long-range interac- amounts of data are generated from the analysis tive studies. However, while public repositories tions, such as those used to establish chromatin of protein-chromatin interactions and epigenome represent an extremely rich source of informa- interactomes. modification, global transcription profiling, chro- tion, there are two major drawbacks: firstly, the The QC database is available to the scientific matin accessibility and its three-dimensional absence of quality information that is associated community via a dedicated web portal (www.ngs- organisation. Collecting all this information in to the various datasets; and secondly, the limi- qc.org). This portal also provides users with the databases like GEO involves complementing tations of existing computational tools for explo- possibility to compute quality grades for their ‘classical’ molecular biology with data-driven ration and data integration. As a result these own unpublished datasets and retrieve a detailed science. The challenge of this data-driven science important reservoirs of knowledge are largely QC report. Such reports can be also obtained for is to integrate large amounts of datasets in such unexplored and underexploited. each of the datasets present of the QC database. a way that we can extract and model regulato- To address the first issue, a quality control The aim is to provide extensive quality infor- ry systems (signalling, transcription regulation, (QC) system was developed, applicable to any mation about public datasets, such that the scien- epigenome, chromatin architecture) and circuits type of datasets generated by massive paral- tific community is able to add quality as a param- (gene-regulatory networks) and identify key play- lel DNA sequencing that involved a sample- eter in their data exploitation and integration ers, which altogether account for the functional enrichment procedure (ChIP-seq and enrich- efforts. If widely used, the resource will improve complexity of a living system (cell, organ) and ment-related assays). Importantly, in contrast data quality and the value of results obtained its physiological and pathological fate transitions to other described quality metrics1, it does not from data mining and integration. (cell lineage generation, pathogenesis like tumo- require prior peak calling strategies, nor does it rigenic transformations) in the context of the involve inter-datasets comparisons (IP versus Marco A. Mendoza Parra & Hinrich Gronemeyer global system. input; inter-replicate comparison), such that the REFERENCES Large collaborative efforts like ENCODE, computed QC metrics reflect the quality of the 1 Landt, S. G. et al. Genome Res 22, 1813 – 1831, (2012). modENCODE, the NIH Roadmap Epigenome concerned dataset directly. Briefly, the QC algo- 2 Mendoza-Parra, M. A., Van Gool, W., Mohamed Saleem, project, the European BLUEPRINT consortium, rithm evaluates the distortion of the enrichment M. A., Ceschin, D. G. & Gronemeyer, H. Nucleic Acids Res 41, but also independent laboratories all over the patterns as a consequence of their reconstitution e196, (2013).

network. In 2012, she was awarded an ERC On the move Grant. “We want to understand exactly how early MARIA-ELENA TORRES-PADILLA, mammalian embryonic development is regulated and how chromatin and nuclear organization recently elected EMBO Member, will direct changes in gene expression and cellular become the director of the newly plasticity,” said Torres-Padilla, explaining the founded Institute of Epigenetics and core objective of her work. She is planning to recruit top junior group leaders in the areas of Stem Cells at the Helmholtz Centre epigenetics and stem cells to the new Institute. Munich, Germany. Prior to taking up the new position, she worked with her team of scientists at the Institut de orres-Padilla is a leading expert in the field Génétique et de Biologie Moléculaire et Cellulaire of chromatin research and developmental (IGBMC) in Strasbourg, France. Her new appoint- Tepigenetics. Her research activities as insti- ment should also help forge new scientific part- tute director will focus on how epigenetic infor- nerships between France and Germany. mation influences cellular plasticity during early The Mexican scientist is optimistic, but recog- mammalian development. EMBO has played a nizes the future challenges: “We want to use this vital role in her scientific career. fresh impetus to advance our scientific knowl- Originally from Mexico, she was an EMBO edge on the molecular mechanisms underly- Fellow during her postdoctoral research in ing totipotency and epigenetic reprogramming.” the group of Magdalena Zernicka-Goetz at the These topics, largely inspired by hypothesis-driv- University of Cambridge. Later on, she was elect- en methodologies, should remain at the heart of

25 years of molecular medicine Headed by EMBO Member DOUGLAS HIGGS, the MRC Weatherall Institute of Molecular Medicine (WIMM) at the University of Oxford celebrates an anniversary this year

This image, taken on an upright Zeiss confocal microscope, shows the vasculature and heart (green) and the blood cells (red) of a live 10 day old transgenic zebrafsh larvae. Image credit: Jana Koth/Patient Lab/WIMM/ ust over 25 years ago, the MRC Weatherall (WTCHG) to create a collaborative facility for Wolfson Imaging Centre Oxford. institute of Molecular Medicine (WIMM) analyzing the biology of single cells. Jat the University of Oxford first opened its doors. Led by Sir David Weatherall, one of the Open to genome engineering most prominent clinicians of the 20th century, Over the past few years there has been some approaches and cutting-edge techniques. The the institute pioneered the concept of applying debate over whether model organisms are appro- ultimate goal is to harness these technologies to newly developed techniques in molecular and priate for studying human genetic diseases. Many engineer primary human stem cells to ameliorate cellular biology to understanding and treating aspects of research ongoing at the institute are or cure human genetic diseases. human diseases. Today, the WIMM hosts 45 explored using model organisms, but increasingly research groups and approximately 500 research- researchers are also studying human diseases New Bioinformatic Centre ers and support staff who to this day continue using human resources. Genome editing tech- In recent years, the ability to extract huge to push forward the boundaries in translational niques are used to manipulate these models and amounts of information about the genetic make- medical research. recently a facility for genome engineering has up of patients suffering from different diseases When the WIMM was established in 1989, been established which uses both conventional has ushered in a new era of molecular medicine, the concept of molecular medicine was still very but analyzing these vast and complex datasets novel, but the institute has led the way in advanc- requires an enormous amount of skill, exper- ing the field ever since its inception. Early accom- tise and computing power. The WIMM and the plishments include the diagnosis and treatment WTCHG have joined forces to recruit computa- of the world’s most common inherited anaemias; tional scientists to work in the institute’s new understanding how T cells are activated during MRC CRI Bioinformatic Centre, which will open an immune response; and developing vaccines to in Spring 2016 thanks to a £2.6m investment from protect against meningitis. the Medical Research Council and the University In 2012, when EMBO Member Douglas of Oxford. Higgs was appointed as the new Director of the Recent investment from the Wolfson WIMM, the expansion of molecular medicine Foundation and the MRC enabled the institute had produced many new biomedical institutes. to build the Wolfson Imaging Centre, which Consequently, the WIMM concentrated its inter- includes facilities that enable super resolution ests on specific research areas. Today, research at imaging. This in turn has enabled the WIMM to the WIMM focuses on haematopoiesis, immunol- collaborate with other imaging groups in Oxford ogy and inflammation, stem cell biology, cancer such as Micron and NanO to build one of the biology and a range of associated genetic diseas- most extensive imaging programmes in Europe. es. At present, about one third of senior inves- The emphasis on translational medical The emergence of a variety of super- tigators are clinically trained, allowing critically research is reflected in the institute’s strong resolution microscopy techniques are important access to patient samples. support of students pursuing both clinical and enabling the much improved visualization As research at the WIMM has been consoli- non-clinical postgraduate training. The institute of biomolecular structures in cells and tissue dated in recent years, the infrastructure at the currently houses approximately 140 doctoral down to a resolution of <100 nm. Shown institute has been developed in parallel. Over the students supported by a range of funding bodies, in this example is a 3-color STED image of past few years the WIMM has established one including the Wellcome Trust and the MRC. mitochondria (TOM2; red), tubulin (green), of the largest and most versatile FACS facilities and F-actin (blue) in HeLa cells acquired on in Europe allowing researchers to isolate rare a commercial Leica SP8 STED 3X microscope. populations of cells accurately and in abundance. Image credit: Christoffer Lagerholm/WIMM/ More recently this has been supplemented by a Wolfson Imaging Centre Oxford. joint venture between the WIMM and the near- by Wellcome Trust Centre of Human Genetics

©2015 EMBO EMBOencounters | Autumn 2015 | [email protected] 11 RESEARCH HIGHLIGHTS – AWARDS Awards of Excellence A Good Read – Publications EMBO MEMBERS from the EMBO Community 2015 Nobel Prize in Chemistry Women in Science Award from IPSEN Prize for Neuronal Antioxidant role for lipid droplets in a stem cell niche EMBO Member Tomas Lindahl L’Oreal-UNESCO. Charpentier, Plasticity of Drosophila the laureate from Europe, was of the Francis Crick Institute and The 2015 award for Genes, Alex P. Gould (EMBO Member) and colleagues joined by Jennifer Doudna (North Clare Hall Laboratory in UK is Synapses and Psychiatric Cell Press | 8 October 2015 one of the recipients of the 2015 America), Quarraisha Abdool Disorders was shared by EMBO doi:10.1016/j.cell.2015.09.020 Nobel Prize in Chemistry for Karim (Africa), Hualan Chen Members Thomas Bourgeron of Control of REM sleep by ventral medulla GABAergic mechanistic studies of DNA repair. (Asia) and Andrea Gamarnik the Institute Pasteur, France, and (South America). The French neurons He received this prize jointly with David Porteous of the Institute of microbiologist’s work on the Paul Modrich, also of the Francis Genetics and Molecular Medicine, Franz Weber (EMBO Fellow) and colleagues CRISPR-Cas9 technology also Crick Institute, and Aziz Sancar UK. They received it jointly with Nature | 7 October 2015 earned her the Carus-Medal by doi:10.1038/nature14979 of University of North Carolina Mark Bear of the Massachusetts the German National Academy of in the US. The three scientists, Institute of Technology, US. Past Integrin endosomal signalling suppresses anoikis from Sweden, the USA and Turkey Science Leopoldina and the Otto laureates of this award include Johanna Ivaska (EMBO Member), Guillaume Jacquemet respectively, received an equal Warburg Medal 2016. Charpentier fourteen EMBO Members. (EMBO Fellow) and colleagues share of the 855,000 Euros award. has started a new position as a Scientifc Member and Director Nature Cell Biology | 5 October 2015 According to the Nobel Foundation, Ivano Bertini Award doi:10.1038/ncb3250 their work has provided funda- at the Max Planck Institute for Stephen Cusack, Head of EMBL mental knowledge of how a living Infection Biology in Berlin in July. Intensity of a pulse of RSL4 transcription factor Outstation in Grenoble, France, cell functions and is, for instance, synthesis determines Arabidopsis root hair cell size is the frst recipient of the Ivano used for the development of new Academicians of Science – Bertini Award from the company Liam Dolan (EMBO Member), Sourav Datta (EMBO cancer treatments. Academy of Finland Bruker BioSpin. The award recog- Fellow) and colleagues Sirpa Jalkanen from the nises a signifcant achievement in Nature Plants | 28 September 2015 Fellows of the Royal Society for University of Turku and Ilkka doi:10.1038/nplants.2015.138 research that utilises an integra- 2015 Hanski from the University of tive structural biology approach. Complementary activities of TPX2 and chTOG EMBO Members who joined Helsinki have been awarded the constitute an effcient importin-regulated the ranks of the Royal Society honorary title of Academician of Academy of Medical Sciences microtubule nucleation module this year: Stephen Brown, Jane Science by the Academy of Finland. Sarah Teichmann and Ewan Clarke, Stephen Cusack, Michael The title can be held by a maxi- Thomas Surrey (EMBO Member), Johanna Roostalu Birney have been elected to the Häusser, Laurence Hurst, Jane mum of sixteen Finnish scientists (EMBO Fellow) and colleagues Fellowship of the Academy of Langdale, Gero Miesenböck, and scholars at a time. Nature Cell Biology | 28 September 2015 Ketan Patel, Bryan M. Turner and Medical Sciences in recognition of doi:10.1038/ncb3241 2016 Croonian Medal and their excellence in research and Frank Uhlmann. Transcriptional plasticity promotes primary and Lecture innovative application of scientifc Li Jiayang and Susan Lindquist acquired resistance to BET inhibition Enrico Coen of the John Innes knowledge. have been announced Foreign Johannes Zuber (EMBO Member), Felix Muerdter (EMBO Centre has been awarded the Members of the Royal Society. Portugal’s Medal of Merit Fellow) and colleagues Royal Society’s prestigious Henrique Veiga-Fernandes Nature | 14 September 2015 Croonian Medal for his work to doi:10.1038/nature14898 understand how the shapes of of the Institute of Molecular biological structures, such as Medicine in Lisbon, Portugal, was Translational arrest by a prokaryotic signal fowers and leaves, arise through distinguished with the honour recognition particle is mediated by RNA interactions development and evolution. of Commander of the Ordem Roland Beckmann, Irmgard Sinning (EMBO Members), Militar de Sant’Iago de Espada Daniel Wilson (EMBO Young Investigator), Bertrand René & Andrée Duquesne Prize by the President of Portugal for Beckert (EMBO Fellow) and colleagues Hinrich Gronemyer of the his contributions to science and Nature Structural & Molecular Biology | Institute of Genetics and internationalization. 7 September 2015 doi:10.1038/nsmb.3086 Molecular and Cellular Biology Susan Lindquist’s admission into Australian Academy of Health (IGBMC) in Illkirch, France, Small RNA-based feed-forward loop with AND-gate the Royal Society and Medical Sciences received the René & Andrée logic regulates extrachromosomal DNA transfer in Duquesne prize of the French Frank Gannon of the QIMR Salmonella Dame Commander of the Order Berghofer Medical Research La Ligue Contre le Cancer worth Jörg Vogel (EMBO Member) and colleagues of the British Empire Institute, Australia, has been 75,000 Euros. Proceedings of the National Academy of Sciences | 11 August 2015 Frances Ashcroft of University elected member of the newly doi:10.1073/pnas.1507825112 of Oxford has been made a Dame IBRO-Kemali Prize for Research established Australian Academy of Commander of the Order of the Casper Hoogenraad has been Health and Medical Sciences. Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol British Empire for “services to awarded the 2016 IBRO-Kemali Umeå University Medal of medical science and the public International Prize for Research Agnieszka Chacinska (EMBO Installation Grantee) and understanding of science” in the in the Field of Basic and Clinical Honour colleagues Queen’s Birthday Honours List. Her Neuroscience for his “outstanding Bernt Eric Uhlin, director of The Nature | 5 August 2015 groundbreaking research into a work on cytoskeleton dynamics Laboratory for Molecular Infection doi:10.1038/nature14951 rare genetic form of diabetes has and intracellular transport in Medicine Sweden, receives the Endothelial depletion of murine SRF/MRTF provokes enabled many patients born with neural development and synaptic Medal of Honour from Umeå intracerebral hemorrhagic stroke the disease to switch from insulin plasticity.” The prize, amount- University. Bernt Eric Uhlin has Alfred Nordheim (EMBO Member) and colleagues injections to tablet therapy. ing to 25,000 Euros, is awarded been honoured for his contri- Proceedings of the National Academy of Sciences | 27 Juli 2015 every two years to a researcher butions to the university and doi:10.1073/pnas.1509047112 L’Oreal-UNESCO Women in under the age of 45, who has the development of the strong Science Award made important contributions research environment in infection Parent-progeny sequencing indicates higher Emmanuelle Charpentier is one in the feld of basic and clinical biology and molecular infection mutation rates in heterozygotes of the fve recipients of the 2016 neuroscience. medicine. Laurence D. Hurst (EMBO Member) and colleagues Nature | 15 July 2015 doi:10.1038/nature14649

Targeting melanoma with NT157 by blocking Stat3 Appointments and IGF1R signaling EMBO YOUNG INVESTIGATORS EMBO FELLOWS Alexander Levitzki (EMBO Member) and colleagues Oncogene | 29 June 2015 EMBO Young Investigator Panayiota Poirazi of the Former EMBO Fellow Andrea Puhar has become a doi:10.1038/onc.2015.229 Institute for Molecular Biology and Biotechnology new group leader at the Laboratory for Molecular in Heraklion, Crete, has been elected as chair of the Infection Medicine Sweden. Primate-specifc endogenous retrovirus driven FENS-Kavli Network of Excellence. The network – transcription defnes naïve-like stem cells Former EMBO Fellow Santiago Zelenay has recently founded in May 2014 – is a joint endeavour of the joined the Cancer Research UK Manchester Institute Laurence D. Hurst (EMBO Member) and colleagues Federation of European Neuroscience Societies and to establish the Cancer Infammation and Immunity Nature | 15 October 2014 the KAVLI Foundation. Group. doi:10.1038/nature13804

THE EMBO EMBO JOURNAL Molecular Medicine

DDSR1/hnRNPUL1 DDSR1/hnRNPUL1 Activation depletion c-Fos PHD1 BSTrh P DDSR1 Infanticide Rap80 Rap80 Brca1 Brca1 Brca1 p53 p53 hnRNPUL1 Brca1 Rap80 Rap80 Brca1 Brca1 Brca1 Brca1 Rap80 Rap80 GABA- p53 p53 Rap80 Rap80 ergic XPB DDSR1 Rap80 Rap80 Brca1 Parenting hnRNPUL1 Brca1 cMPOA RESEARCH ARTICLE Activation DNA damage c-Fos/ optogenetics Reducing resistance to DNA repair by HR Impaired HR chemotherapy by inhibition of RESEARCH ARTICLE Brca1 Brca1 Brca1 Brca1 RESEARCH ARTICLE PHD1 Rap80 Rap80 Rap80 Rap80 A cell–based model system Chemotherapy remains the most Switching on paternal links chromothripsis with Rap80 Rap80 Brca1 Brca1 behaviour widely used cancer treatment, and hyperploidy much attention has been paid RESEARCH ARTICLE Male mice dramatically change to the mechanisms underlying A remarkable observation emerging their social behaviour towards chemotherapy resistance. Sofie from recent cancer genome lncRNA DDSR1 maintains newborn pups after mating Deschoemaeker and a research analyses is the identification genome stability and cohabitation with pregnant team led by Massimiliano Mazzone of chromothripsis as a one–off females. Japanese neurobiologists have shown that blocking the genomic catastrophe, resulting in Long non-coding RNAs (lncRNAs) now report in The EMBO Journal PHD1 oxygen sensor hinders the massive somatic DNA structural are important players in diverse that activation of defined small activation of p53, a transcription rearrangements (SRs). Largely biological processes. Upon DNA regions of the mouse brain factor that aids colorectal cancer due to lack of suitable model damage, cells activate a complex determine whether a male mouse (CRC) cells in repairing themselves systems, the mechanistic basis signaling cascade referred to as will show infanticidal or paternal and thus resisting chemotherapy. of chromothripsis has remained the DNA damage response (DDR). behaviour. A team led by Kumi These findings indicate that PHD1 elusive. We developed an Using a microarray screen, we Kuroda of the RIKEN Brain Science inhibition may have valuable integrative method termed identify here a novel lncRNA, Institute in Japan monitored the therapeutic potential. “We “complex alterations after DDSR1 (DNA damage-sensitive trace of neuronal activation of demonstrated that PHD1 can affect selection and transformation RNA1), which is induced upon nine histologically defined areas the way colorectal cancer responds (CAST),” enabling efficient in DNA damage. DDSR1 induction in the mouse forebrain. Two of to the three most common vitro generation of complex is triggered in an ATM-NF-κB these areas showed strikingly chemotherapeutic drugs used to DNA rearrangements including pathway-dependent manner by distinct activation patterns treat CRC today. By blocking PHD1, chromothripsis, using cell several DNA double-strand break depending on whether the male we rob CRC cells of their ability to perturbations coupled with a (DSB) agents. Loss of DDSR1 mouse had displayed parental harness p53 to the cell-repair yoke, strong selection barrier followed impairs cell proliferation and care or aggression towards pups even when this protein is mutated by massively parallel sequencing. DDR signaling and reduces DNA a few hours earlier. Selective (as often occurs in CRC). That We employed this methodology repair capacity by homologous inactivation of these brain areas means the CRC cells are exposed to characterize catastrophic SR recombination (HR). The HR confirmed that they were indeed to the full DNA damage caused by formation processes, their temporal defect in the absence of DDSR1 is responsible for controlling paternal these genotoxic drugs, resulting in sequence, and their impact on marked by aberrant accumulation versus infanticidal behaviour. greater cell death and thus a better gene expression and cell division. of BRCA1 and RAP80 at DSB sites. Moreover, the scientists could response to the chemotherapy and, Our in vitro system uncovered In line with a role in regulating trigger development of sustained ultimately, an improved outcome,” a propensity of chromothripsis HR, DDSR1 interacts with BRCA1 infanticide suppression even in Deschoemaeker explained. The to occur in cells with damaged and hnRNPUL1, an RNA-binding previously aggressive virgin males. research opens the door to the telomeres, and in particular in protein involved in DNA end “The most striking finding in our design and validation of PHD1- hyperploid cells. Analysis of resection. Our results suggest a studies was that the observed specific inhibitors in colorectal primary medulloblastoma cancer role for the lncRNA DDSR1 in activation patterns did not depend cancer patients, with the aim genomes verified the link between modulating DNA repair by HR. on whether the male mouse had of increasing their sensitivity to hyperploidy and chromothripsis in A BRCA1–interacting lncRNA regulates actually performed infanticide or currently used chemotherapeutic vivo. CAST provides the foundation homologous recombination parenting, or had only intended treatments. for mechanistic dissection of Vivek Sharma, Simran Khurana, to do so upon being indirectly Nard Kubben, Kotb Abdelmohsen, PHD1 regulates p53–mediated colorectal complex DNA rearrangement Philipp Oberdoerffer, Myriam Gorospe, presented with a protected pup”, cancer chemoresistance processes. Tom Misteli remarked Kuroda. Sofe Deschoemaeker, Giusy Di Conza, Read the paper: Sergio Lilla, Rosa Martín-Pérez, A cell–based model system links http://dx.doi.org/10.15252/ Distinct preoptic–BST nuclei dissociate Daniela Mennerich, Lise Boon, chromothripsis with hyperploidy embr.201540437 paternal and infanticidal behavior in mice Stefanie Hendrikx, Oliver DK Maddocks, Balca R Mardin, Alexandros P Drainas, Yousuke Tsuneoka, Kenichi Tokita, Christian Marx, Praveen Radhakrishnan, Sebastian M Waszak, Chihiro Yoshihara, Taiju Amano, Hans Prenen, Martin Schneider, Joachim Weischenfeldt, Mayumi Isokane, Gianluca Esposito, Arthur J Huang, Johanna Myllyharju, Thomas Kietzmann, Adrian M Stütz, Benjamin Raeder, Lily MY Yu, Yuri Odaka, Kazutaka Karen H Vousden, Sara Zanivan, Theocharis Efthymiopoulos, Christopher Discover more great Shinozuka, Thomas J McHugh, Massimiliano Mazzone Buccitelli, Maia Segura–Wang, Kumi O Kuroda Read the paper: Paul Northcott, Stefan M Pfster, research at Read the paper: http://dx.doi.org/10.15252/ Peter Lichter, Jan Ellenberg, Jan O Korbel http://dx.doi.org/10.15252/ emmm.201505492 Read the paper: embopress.org embj.201591942 Source: http://www.vib.be http://dx.doi.org/10.15252/msb.20156505

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A tribute to Gottfried Schatz 1936 – 2015 EMBO secretary General (1985 – 1989) Member of the Fellowship Committee (1979 – 1982), and Member of the Science and Society Committee in 1999 © Marco Borggreve

ottfried “Jeff” Schatz was proud of having been impressed by the elegance of Schatz’ experi- Duve’s quantitative cell fractionation, for out of been trained as a chemist– in the clas- ments, the simplicity of his explanations, and the such basic principles, with each student and post- Gsic physical chemistry sense – where the accessible way, in which complex phenomena doc he trained, Jeff Schatz was helping spawn the taste and smell of chemicals were as important were explained. new field of molecular cell biology. as precision measurements for guiding one’s scientific insight. But Jeff Schatz’ brilliant scien- Fundamental discoveries Exquisite gentleman and mentor tific career was actually as a biochemist who What were Jeff Schatz’ discoveries? First, he and Jeff Schatz was extremely gifted. He was gifted in embraced and dissected two fundamental ques- his first PhD student, Ellen Haslbrunner, showed the sense of an artist, and possibly the insight that tions of cell biology: “Where does the energy- by biochemical fractionation that mitochondria made him a great musical talent was the same producing engine of our cells come from?” and contain DNA, i.e. their own genome buried with- that enabled him to render biological complex- “How are these mitochondria made?” in the membrane-bound organelle. He showed ity elegantly simple. Above all, Jeff was passion- During 35 years the concept of “mitochondrial that mitochondria did not arise de novo, but were ate and caring, he was an exquisite gentleman of biogenesis” became synonymous with Schatz’ self-reproducing: even anaerobically grown yeast the sort that harkens back to a lost age, and he name. Two words that seemed to hide an infinite that appeared to lack mitochondria contained never stopped believing that great minds like his complexity of details were made simple by his pro-mitochondrial particles within which their should share whatever insight they have about razor-sharp intuition and gifted explanations. Jeff genome was preserved. Proteins encoded and the richness of life with as many people as possi- Schatz studied mitochondria in budding yeast synthesized within mitochondria would then ble. Beyond those trained in his laboratory, Jeff partly because yeast is one of the few organisms assemble with others that were nuclear-encoded Schatz schooled countless young scientists in that can live with non-functional mitochondria, and synthesized in the cytoplasm to form one of the art of giving scientific talks. He wrote and in a form that was dubbed by French geneticists nature’s most elegant organelles. lectured elegantly about science and nature to the petite. Inspired by the implications of such genet- Again using biochemical approaches, Schatz general public, and he attempted to enlighten our ic studies, Schatz used biochemical approaches showed that only 13 proteins were encoded by leaders – in politics, industry and in academia – to decipher the interplay of two genomes – the the mitochondrial genome. The rest of the protein about the true nature of the scientific enterprise. mitochondrial and the nuclear – and the machin- machinery that carries out fatty acid and sugar He played a major role in European society at ery that assembles the proteins they encode into catabolism, electron transport and oxidative large by fostering awareness of the importance of the elegant electron transport chain. This cascade phosphorylation had to be specifically imported scientific knowledge in our modern life. of enzymes which extracts energy from the oxida- from the cytoplasm, processed and then assem- For Jeff, culture and science were one; creativ- tion of sugars and fats to generate the high-energy bled with the mitochondrial-encoded counter- ity he saw as a human gift that one must always intermediate ATP, was for Schatz one of nature’s parts. His approach was classically biochemical, foster and encourage, and his ability to write criti- great miracles. relying on fractionation and reconstitution. It was cally yet insightfully about scientific research and Rarely has a field been so overwhelmingly quantitative and molecular, yet with it he could academic training set him apart from any other shaped by one person. Results from the Schatz explain many fundamental principles of cell biol- scientist alive. The entire world of science – not laboratory became embodied in textbooks shortly ogy. Piece by piece his laboratory made sense merely Swiss science – has lost one its greatest after they were published – so compelling were of sequences that target proteins to the mito- spokesmen. the elegance and logic of his work. Of course he chondria, of membrane channels that regulate was not alone in the field of mitochondrial biogen- translocation, and the processing and re-folding Susan M. Gasser, Director esis. The discoveries arising from the Schatz labo- machinery that assembles the electron transport Friedrich Miescher Institute for Biomedical Research ratory ricocheted off those of Walter Neupert, a chain, requiring two membranes, two compart- highly successful, Munich-based biochemist, ments, and an asymmetric spatial organization who studied a similar phenomenon in the mold of enzymes. I remember how carefully he taught Neurospora. But even Walter Neupert must have me the principles of enzymology and Christian de

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