imprint Editorial staff Russ Hodge (rh), Vera Glaßer (vg)

English

imprint

Publisher

Chair of the Board and Scientific Director of the Max Delbrück Center for Molecular Medicine (MDC) Professor Walter Rosenthal Robert-Rössle-Str. 10, 13125 Berlin-Buch

Editor-in-Chief

Josef Zens (jz), Maimona Id, deputy chief (Id) MDC, Communications Department Robert-Rössle-Str. 10, 13125 Berlin [email protected] Editorial staff

Russ Hodge (rh), Vera Glaßer (vg) Authors Klaus Rajewsky, Emanuel Wyler, Michael Hinz, Lucy Patterson, Oksana Seumenicht, Alexander Loewer, Inbal Ipenberg, Nadine Richter, Cornelia Hainer, Nuria Cerdá-Esteban, Kristin Petzold Translation Lynda Lich-Knight,

Russ Hodge, Dietmar Zimmer, Timkehet Teffera Coverphoto David Ausserhofer Proofreading Kirstin Müller, Michaela Langer Design a1grafik, Berlin Production Druckerei Conrad GmbH Breitenbachstraße 34-36, 13509 Berlin Paper: ProfiBulk, (FSC certified) Circulation 1.500 Copyright Reprint only with permission.

Please contact the editors for permissions. ISSN 2192-6956

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Editorial

Dear readers, Not all scientists can boast such excellent research conditions or the security to immerse themselves in research that are a hallmark of the MDC. In our alumni portrait on page 45, Ahmet Abdelaziz touches on the difficulties of conducting research in Egypt during the Arab Spring. Apropos Egypt: when PhD student Douaa Mugahid sent an email describing Eid al-Adha, the Feast of Sacrifice, the response was extremely positive. We want to build on this initiative and introduce a loose series of articles presenting our cultural diversity at MDC. Inbal Ipenberg launches the series with a personal take on the Jewish Passover holiday, Pessach (p. 54). Another kind of cultural difference is the focus of our cover story, ‘The Bridge between University Hospital and Research’, starting on page 8. What is work going to be like at the new Berlin Institute of Health (BIH)? How will things change for you? We have collected some answers. Last but not least, there have been some changes at imdc: we have a new editor (see photo) and a new layout. Many people had asked us to produce what the Germans call a ‘Wendeheft’, a bilingual issue which you can turn around to read either the German or the English version. This is it. In the future, research at MDC will have a section of its own. Themes related to the MDC Juniors in PhD studies or vocational training are already bundled under ‘Max’. What has not changed is our intention to deliver reliable information and fascinating stories revolving around MDC and the Buch Campus – such as all the coverage of our big 20th anniversary celebrations. At imdc we want to keep in touch with the joys and successes of your everyday work, but also follow up the challenges that all of us on campus have to tackle. To do so, we need your help: send us your ideas and the themes that are important to you! Happy reading! Maimona Id and Josef Zens

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Contents

08

20

The BIH – the bridge between hospital and research – cooperation of medicine and natural science

Searching for alternatives to embryonic stem cell therapy

Coverstory

Research

08

Two Perspectives, One Goal

16

Small, but potent

12

The Bridge between Hospital and Research

19

‘Esprit d'échange’

15

Zooming in on Systems Medicine

20

Demystifying Regeneration

23

Highlight Paper: A new target in the battle against deadly brain tumors

26

The Case of the Short-fingered Musketeer

29

Of Mice and Models

31

The Immune System: a partner in the fight against cancer

32

News

34

Winners of the 2012 Image Contest

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46

60

64

A Finger on the Pulse of Science – the teacher training programme ‘LTL’

‘Pastoral Care’ for PhD's – the new ombudswoman

Comic art in architecture tells an amazing story

insights

Ma X

Campus

36

‚Congratulations MDC!‘

60

The ‘PhD’s Pastoral Caregivers’

64

40

20 Years of Science

62

‘Follow Your Heart!’

42

20 Years of MDC - Part 2

44

LinkedIn is good,

‘Trainee missing. Are we under threat from magnetic chaos? ’

face-to-face is better 45

Cairo, the City that never sleeps

46

A Finger on the Pulse of Science

49

Always an Open Ear

50

Strong Partners from China

52

Running the Runway

53

Politics meets Science

54

My Passover

56

We’ll share a cup

57

In a nutshell

58

MDC Summer Research Camp

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5

Standpoint

B0ston

berlin or Boston? Boston From 2001 to 2012, I worked at Harvard University in Boston. Most of my collaborators in the lab were postdocs. They came from many parts of the world, the US, Europe and Russia, and increasingly from Asian countries like India and China. The Chinese postdocs would sometimes come directly from China, but most had already graduated at a US university. These were amongst the most highly selected young scientists one can imagine – a few of thousands accepted at one of the top Chinese universities, followed by a second round of selection to enter into the US academic system. The dream of all those youngsters was and is to do their postdoc at one of the top US academic institutions: the US are clearly number one as a scientific and educational powerhouse, American English is the world’s scientific language, and the multi-cultural USAmerican society offers full participation to everybody; so for the young immigrants the option of ‘naturalizing’ is a realistic perspective if going back to

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or

At German science locations English has still not established itself in all areas. And this is losing us good postdocs who prefer to go abroad to Englishspeaking countries, says Senior Scientist Klaus Rajewsk y. Postdoc Emanual Wyler, on the other hand, thinks Berlin has the edge when it comes to attracting junior researchers.

their home countries turns out to be difficult. Of course, scientific excellence is and remains the prime criterion by which top postdoc candidates choose their destination, and there is a competition for the best postdocs everywhere, in the US as much as in Germany and Europe. But it is also evident that we have a much harder time here, simply because for young foreign scientists, particularly those from other continents, the environment we offer is not a priority on the wish list: integration of foreigners is not a natural element of our culture, and the requirement for scientists to communicate in English, not German, accentuates this problem. Even in our scientific and academic institutions, not to speak of public administrations, we have not yet been able to fully establish English as a working language all through the scientific and administrative layers. To get

the best young talent attracted to us as much as to the US will require opening ourselves up so that young foreign scientists perceive our country as a place where they can easily communicate, and can thrive as fully accepted and appreciated members of society. Let’s take a next step in this direction locally, here at MDC, by implementing a fully bilingual infrastructure! Klaus Rajewsky

Berlin? Boston or berlin? Berlin

and Boston are evidently not the same. The quality and density of research institutions in Boston, with Harvard Medical School, MIT, etc. is unmatched, both in the US and internationally, and the situation will remain that way for a while. This does not mean that Berlin cannot raise its ranking in terms of world-class research locations. Brilliant people can be found in Berlin as well as in Boston, although different things attract them here. English is the worldwide ‘lingua franca,’ and this will not change in the near future. Hence the classical immigration countries England and USA will always be more accessible for people from around the world, compared

to many German cities. However, Berlin as the European melting pot of our day needs to fear no comparison when it comes to internationality. Immigration, especially of younger people from all over the world, is constantly increasing. A high quality of life, a rich cultural scene and affordable rents attract talented scientists with broad interests who might not consider moving to a closed campus near a small town. Other aspects of life make Berlin attractive as well: postdocs, who play leading roles in most research projects, are at an age when the idea of raising a family is high on their list of priorities. While childcare can be very expensive in the US, it comes at a very low cost here. This is particularly decisive in a woman's ability to continue her research career. To relinquish talented researchers due to lack of childcare is simply a waste of talent. The possibility of completing a PhD in three to four years makes German universities and research institutes attractive, compared to the US, for students coming from Asia and many other parts of the world. Additionally, students usually have a secure salary that will be paid until they get their degree. This is enhanced, particularly at MDC, by a bonus that is awarded when students are successful and publish papers. And it is extremely important to note that students in this

system usually are able to finish their PhD without incurring a large debt, which indeed can occur in England or the US. Still, German institutes have a lot to do before they are likely to significantly raise their world-wide ranking. The problem is not exclusively one of carrying out cutting-edge research and publishing in high-ranking journals. There is an absence of mid-level faculty in academia, resulting in a lack of career perspectives. It is usually very difficult to obtain a position in academic research without a full professorship; this weakens Germany’s position in the competition for talent. Additionally, further internationalization would be a boon to many institutes and regions. Here the aim should not only be to acquire brilliant researchers from abroad in hopes of imitating successful international projects. Germany has many strengths; what we need to do is focus on them and foster their growth. Emanuel Wyler

Berlin

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coverstory

Cov erstory

W

T wo Perspectives,

One Goal T e x t Ma i m o n a Id

P h ot h o s Dav i d Au s s e r h o f e r

At the Berlin Institute of Health ( BIH ), natural scientists and medical practitioners are about to take their collaboration to the nex t level. A good moment for imdc to explore these t wo dif ferent cultures.

hen Verena Schöwel was a medical student, she had very little idea of what the curious term ‘dive-bomber sound’ was supposed to mean. ‘It was the ultimate running gag. We couldn’t imagine why we were supposed to learn this,’ she recalls. Today she knows. She often hears this ‘divebomber sound’ in the outpatient department when abnormal muscle activity is being recorded electronically. It indicates one of the rare incurable diseases Verena Schöwel invesigates at the Buch Campus. In the ‘Muscle Research Unit and University Outpatient Clinic for Muscular Disorders’, headed by Professor Simone Spuler, outpatient care and research are closely linked. It is part of the Experimental and Clinical Research Center (ECRC), an institution run jointly by MDC and Charité - Universitätsmedizin Berlin. Theoretical scientists and clinical researchers like Verena Schöwel collaborate here on new approaches to the diagnosis, prevention and therapy of cardiovascular and metabolic disorders, cancer and neurological diseases. Patients who come to the Outpatient Clinic for Muscular Disorders are often in distress, because no one has yet been able to diagnose their condition. What appeals to Verena Schöwel about her job is diagnosing these people correctly. The young physician is not first and foremost out to find a cure, but an unequivocal diagnosis so that her patients can profit from modern research results as fast as possible. ‘To heal people is certainly a noble goal, but I’ve seen too many incurable diseases,’ she says. Her objective is to apply an analytical approach to decode a disease scientifically. This was one of the reasons why the medical practitioner went into research.

Patient Olivia L. knows she is in good hands as she is treated by physician Verena Schöwel.

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coverstory

Scientist Philipp Maass (with TA Irene Hollfinger) has lots of fun in the lab, even though he spends more and more time at the computer applying for grants.

Motivation through patient’s contact

Philipp Maass has a similar motivation. The Molecular Biologist works at MDC and ECRC. As a member of the research group on Genetics, Nephrology, Hypertension, and Vascular Injury, he is investigating gene regulation and skeletal development. Philipp Maass knew from the start that he wanted to work in human clinical research. ‘I’m really driven by the idea of decoding a disease and, ideally, helping patients in the process.’ His professor, Friedrich

Luft, who has been Director of ECRC since 2007, is one of the pioneers who established translational medicine on the campus in the 1990s. Among other things, Philipp Maass works with him on a research project that explores the hereditary disease of a far-flung Turkish family. They discovered that a certain region on chromosome 12 causes hypertension and goes along with shortened fingers and toes (see article on p. 20). Three years ago, Philipp Maass travelled to Eastern Anatolia with clinical researchers to take new specimens from the patients on the

spot. This was a formative experience for the natural scientist who rarely comes into direct contact with patients. ‘For years I’d been processing anonymous specimens, now I can relate to the disease in a new way. It boosted my motivation even more,’ he reports enthusiastically. ‘Research is certainly a tough business…’

Physician Verena Schöwel built a mouse model for her research project, which was a challenge. Medical studies and

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coverstory

training had not prepared her sufficiently for the demands of research. ‘It cost me a lot of sweat and tears,’ she recounts. Now she feels more at home in the lab than the hospital. ‘Research is very exciting and intellectually demanding, especially for us doctors. We have to compete with the other disciplines all the time,’she emphasises. It took her three or four years to establish her place in research and be able to discuss with colleagues from basic research on an equal footing. What struck her was the difference in approach and mindset between physicians and natural scientists. ‘There’s a cliché about theoretical researchers being overly meticulous and obsessed with detail,’ she comments mischievously. But she likes that. ‘Because this precision and perpetual questioning are the very qualities that matter in research.’ She has also learned a lot Philipp Maass cuts out DNA from a gel.

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about herself. ‘In research you have to have a high frustration threshold. At the beginning of my research career, I got disappointed very quickly when I’d invested a lot of effort and ended up with a negative result.’ Create perspectives for clinical researchers

Verena Schöwel realised early on that she would not be able to work in the clinic and in the lab at the same time. Three years ago, the mother of an eight-month-old took leave of absence from the hospital ward in order to focus exclusively on science. She applied for a place on ECRC's clinical training programme KAP. This two-year programme targets post-doc physicians at Charité who aspire to a career in science. In an MDC working group they acquire the necessary tools to research

independently, learn to compose articles and third-party funding applications as well as how to establish their own working group. During this process they are regularly evaluated by theoretical researchers. ‘Recruiting and diagnosing patients and collecting specimen materials for clinical research trials all take time. To establish a successful scientific project with a clinical background, physicians and natural scientists must interact closely, and they need support in doing so,’ Philipp Maass believes. Another problem with cross-cutting projects is the lack of opportunities for clinical researchers like Verena Schöwel who do not want to turn their backs on clinical practice altogether. The conditions for young natural scientists also leave room for improvement. There were times when Philipp Maass did not know whether his application for third party funds would

coverstory

Clinician Verena Schöwel and basic researcher Tobias Timmel are working hand in hand as they carry out research into new types of therapies.

be approved in time. ‘Looking after the finances and making sure that personnel costs are covered takes a lot of time and energy and distracts you from science. Too much red tape and politics can be a real burden on good research,’ he says.

Microscopically thin slices of patient tissues are a crucial resource in the study of human diseases.

Verena Schöwel and Philipp Maass hope that the Berlin Institute of Health (BIH) will bring further career opportunities and new inspiration for colleagues at MDC and Charité. A hint of scepticism remains. ‘BIH is still a bit of a hazy construct that has to be

filled with life. Building networks takes time,’ the natural scientist emphasises. Both of them think it is important to keep working on the connection between basic research and clinical practice every day to achieve better mutual understanding of their different perspectives. ‘The fact that I’m a doctor is what drives my research work. It was through my patients that I found my way into it,’ Verena Schöwel says. Even if natural scientists and physicians come from different directions, they pursue a common goal. ‘We must continue to build the collaborations and projects between clinical and scientific research that are already shaping the future here on campus, and we must communicate with one another intensively. If we manage to do that, we’ll achieve the ultimate,’ both researchers agree.

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coverstory

The Bridge b e t w e e n Hospital and Research More than 300 million euro will be channelled into the new Berlin Institute of Health (BIH) in the nex t few years. In the run-up to the amalgamation of Charité – Universitätsmedizin Berlin and the Ma x Delbrück Center for Molecular Medicine ( MDC), imdc spoke to MDC’s Professor Walter Rosenthal, Chair of the Board and Scientif ic Director, and Administrative Director, Cornelia L anz. P r oto c o l Ma i m o n a Id, J o s e f Z e n s P h ot h o s D i e t m a r G u s t, Dav i d Au s s e r h o f e r

Prof. Rosenthal, the MDC is one of the 20 world leaders in its field, attracting the cream of the scientific community. Why should it want to get together with another partner? Walter Rosenthal There are

several reasons for this, but the most important one is that the new alliance will drive science. We are on the cusp of a paradigm shift. We already know that apparently unequivocal symptoms like bowel cancer can have different molecular sources. Conversely, a genetic defect can be one of the causes of various diseases. Thus, in the future, doctors won’t spend so much time examining the symptoms but will look into the molecular signature of the disease instead. That’s what we call systemic medicine. Together with a really strong clinical research partner – and I couldn’t imagine a better one than Charité – we’re going to make the paradigm shift to systemic medicine and on towards personalised medicine. Apart from this, it is actually one of our founding principles to apply the findings our basic biomedical research as speedily as possible.

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And I’m not going deny that I’m a bit concerned about the end of the Excellence Initiative. The funding situation for research and teaching could be a lot tighter in five years’ time than it is now. But a subject like Life Sciences, which looks to the future for results, needs additional funding as well. Here the Berlin Institute for Health, as I prefer to call it, will be immensely helpful. The BIH wants to close the gaps in translational research. What does this mean? Walter Rosenthal We’ve

identified two big gaps: the first is the transition from basic research to diagnostics and therapy. Things that work in test-tubes or animal experiments are worlds away from a cure for people. First of all, we have to “translate” them into medical treatment. We want to close this translational gap. And we don’t see it as a one-way street either. Our motto is “from bench to bedside and from bedside to bench.” The second gap is the one between research and clinical activities on the one side and broadly-based applications for

coverstory

hospitals and medical practice, including Public Health, on the other. In the long term, we want to use the results of personalised medicine to draw up strategies for providing medical care for broad sections of the population. Founding the BIH means the MDC is changing its legal form. Why is this necessar y? Cornelia Lanz BIH is due to

become a corporation under public law (KöR in German) which means that in institutional terms, two strong partners, MDC and Charité, will work together in a common research area. This institutional bracket is supposed to help bridge the gap between basic research and clinical research. Both partners, MDC and Charité, will still be legal entities and thus retain their full independence. MDC is a strong brand in science and enjoys high international visibility. This visibility will not be lost when BIH is founded. I think it’s a win-win situation: with the legal rights of a joint corporate entity we can institutionalise and strengthen our cooperation with Charité, but still utilise all the opportunities we have had so far. In order to found the corporation (KöR) we have to have parliamentary

approval at Federal and Land level, and this doesn’t happen overnight. For MDC to become a joint corporate entity its current legal form as a foundation will be changed into that of a corporation (KöR). The process is scheduled to be completed by 2015. How will cooperation be organised until then? Cornelia Lanz We already

want to start this year. And the first funds will be available in 2013, too. So we need general conditions which will be contained in a so-called memorandum of association. This won’t only be signed by the two partners, but by the Federal and Land governments and the Helmholtz Association as well. The contract regulates the BIH’s various management bodies and committees, supervisory council and scientific advisory board which will start work in 2013. It also stipulates that during the transition phase, the finances required to establish the joint research area will come from Helmholtz Association funding. The contract will be based on an evaluation of the joint research programme by international reviewers in May 2013. What opportunities or changes will the BIH hold in store for our staff? Cornelia Lanz One of the op-

portunities will certainly be more employment options. Completely new jobs will be created at BIH as well. However, in the run-up to founding BIH, we on the MDC Board have been very careful to ensure that the employment conditions for our staff won’t change. When BIH is a joint corporate entity of the new BIH, our staff will continue to be paid according to the TVöD pay scale just as they have at MDC. Walter Rosenthal The biggest change for scientists will be new openings for raising funding for their research projects. There will be a major annual call for networking proposals, for example. We want to recognise

excellent individuals and reward them with additional funding of a similar order to the Howard Hughes Program. And there will be targeted top-level recruiting. We are also planning to set up additional graduate schools as well as Master’s and exchange programmes to promote excellent training opportunities for PhD students. This means more jobs in training and extra funds, too. On top of this, new technology platforms and the extension of existing infrastructure are on the BIH drawing board. What sort of career prospects will the BIH offer young, clinical researchers? Walter Rosenthal At pre-

sent, the lack of guaranteed research time and woolly career prospects make a lot of clinicians shy away from a career in science. On the pattern of existing programmes like ECRC’s successful Clinicians Training Programme (KAP), BIH envisages a training and research programme for clinicians in order to provide a protected environment for scientific training. For research you need time and a clear head, which means we must create additional positions to reduce the pressure on upcoming researchers. There will also

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coverstory

be fellowships for medical students to introduce them to translational research at an early stage, even before they have finished their training. And then there are plans to set up a dedicated research programme for “translational postdocs” with a clear focus on systemic medicine.

in major research programmes, often with universities, that do not involve Charité. BIH is a joint initiative to achieve something quite new: to tackle new research issues, to apply new technologies and, especially important, to establish a new culture of cooperation.

Two very self-assured institutions will work together on joint projects under one roof without either having operational power over the other partner. Is it going to work? Walter Rosenthal This is the

Received wisdom has it that doctors and fundamental researchers don’t get on. What’s your response to that? Walter Rosenthal There may

only way it’s going to work. However many common goals we may have, we have different identities and a different mission, and we also have different cultures. We don’t want to interfere with Charité’s patient care or building management, nor would we be able to. And vice versa: as a Helmholtz Centre we are charged with tasks of national importance and participate

two distinct institutions. This is the real added-value of BIH and its legal framework: there will be space for excellent clinicians, pure researchers and for what connects them – translational medicine.

be a modicum of truth in that, but that’s exactly why we’re doing something about it. We want to fuse the different cultures at BIH. I’m familiar with both sides because after my medical training, I worked as a doctor before going into research, if only for a short time. I have colleagues who are at home in both worlds and get on very well indeed. These are the people for whom we want to create space without abandoning our identities as Facts and Figures • BIH – Berlin Institute of Health (German: Berliner Institut für Gesundheitsforschung, BIG) is scheduled to be established in 2015 as a corporation under public law with two joint corporate entities, Charité Universitätsmedizin Berlin and MDC. In the interim, a cooperation agreement will govern collaboration between the two institutions. • BIH will be financed by additional funding from Federal Government and the Land Berlin at a ratio of 90:10 (Helmholtz ratio). A total of 300 million euro has been earmarked for the first five years. • The institute will be operated by a fourmember executive board: the respective chairs of the directorial boards of Charité and MDC, the Dean of Research at Charité and one additional independent member who will chair the board and have a casting vote in the event of parity. • Both joint corporate entities will remain legally independent and free to decide on their own fundamental affairs without interference from the BIH executive board. This includes, for instance, budgetary matters, joint appointments with universities and activities under the Helmholtz Association’s programme-oriented funding (PoF). • A Scientific Council will mentor BIH’s programme; its supreme body will be a Supervisory Council. MDC will retain its own supervisory body and council, but change its legal form to become a corporation.

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coverstory

Zoo mi ng i n on Systems Medicine The research programme at the Berlin Institute of Health ( BIH )

• Strategic recruiting of first-rate staff in clinical disciplines and fields such as Stem Cell Biology, Epigenomics, Metabolomics and Bioinformatics.

Flagship Projects and Infrastructure

Analysis

• Sustained support for research groups. This funding will be allocated to MDC and Charité scientists in a competitive, peerreviewed procedure. Berlin-based universities may apply in conjunction with a partner at MDC or Charité. • Protected research time, laboratory facilities and positions for the entire range of academic staff, from junior researchers to W3 professors. The programme will target young scientists with a clinical background who are interested in translational research.

Our contribution to the future partnership will include valuable model organisms for human disease, in particular mice. For its part, Charité has great expertise in the progression, characteristics and classification of diseases (“clinical phenotyping”). The large number of very thoroughly examined patients is a valuable basis for cohort studies. jz

Systems Medicine

and Conc ept

The research programme will offer opportunities like the following :

the molecular signature of their specific condition. This is a paradigm shift in medicine, which traditionally tended to classify diseases on the basis of their symptoms. To make progress on the journey towards this kind of personalised medicine many disciplines will have to work together, for instance clinicians, molecular biologists and computer experts. Furthermore, we need state-ofthe-art technology platforms, which to some extent we already have at MDC. BIH will essentially address crosssectional themes pertaining to multiple diseases: immunology, cellular and sub-cellular processes, cell degeneration and regeneration, metabolic processes, the genetics of disease and the role of gender differences in disease progression.

Organ Specific

Status

T

he BIH research programme is based on four fundamental principles: interdisciplinarity, translation, excellence and innovation. In this context, translation means the transfer of results generated by biomedical basic research to applications on the patient, whether in diagnostics or therapy. In the long run, results are also destined for use in disease prevention. Systems Medicine is at the core of the research programme: thanks to ever better and faster methods of deciphering processes in cells, among other things with the help of OMICS technologies like proteomics or genomics, we can now read the molecular “signature” of a disease. This in turn makes it much easier for medicine to assign patients to groups (stratification) and treat them according to

Biological Barriers

Immune System

Proteostasis

Congenital Disorders

Metabolism

Genetics

(Sub)cellular machines

Re-/Degeneration

Immunology

Gender

Neuroscience

Cancer

Cardiovascular & Metabolism

Exemplary Research Areas

Cross-Cutting Topics

Achievements & Priorities

The diagram illustrates the paradigm shif t from organ-specific and symptom-oriented medicine towards Systems Medicine. Cross-cutting topics are to be addressed, building on the existing focus on neurological disorders, cancer, cardiovascular and metabolic diseases. Research areas like the immune system or congenital disorders are envisaged. From this pool of topics flagship projects and technology platforms will be defined.

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Research

Research Armin Rehm and Uta Höpken investigate the toxicity of T-lymphocytes to tumor cells.

small, but

potent!

MDC researchers Dr. Uta Höpken and Dr. Armin Rehm explore how a naive immune cell becomes a cy totoxic T cell (CTL), and how it could help combat cancer. T e x t Ma i m o n a Id

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P H oto s Dav i d Au s s e r h o f e r

Research

U

ta Höpken and Armin Rehm have long known what makes for a perfect liaison between clinical practice and basic research. The immunologist and the physician/cell researcher are a couple in their private as well as their professional lives and collaborate on various research projects. Being in different working groups, they are well able to complement each other. Uta Höpken works in the Molecular Tumour Genetics and Immune Genetics research group, Armin Rehm in the Haematology, Oncology and Tumour Immunology group. Their shared focus is on a tiny cell with a powerful effect, the cytotoxic T cell. ‘Apart from the genetic track, i.e. what goes on in the cell core, we are mainly interested in

the post-translational processes,’ Höpken says. These are the basic transport channels and signal transmission mechanisms that govern complex cell functions after protein biosynthesis, and they happen in the cytoplasm. ‘Unfortunately, in our case this is a very narrow space, which makes it a major challenge to analyse the cell,’ the immunologist emphasises. In contrast to other eukaryotic cells, T cells measure no more than nine or ten micrometres. ‘Our trick is to drastically decelerate processes with the help of pharmacological substances, so we can actually visualise them with high-resolution live imaging technology,’ her partner explains. These difficulties have turned T cell biology research into a

niche science. ‘As far as I'm concerned, it’s a core discipline,’ says Höpken. In the context of individualised immune therapy, T cells are a new beacon of hope in the battle against cancer. The first encounter strips cells of their generic potential

T lymphocytes belong to the group of white blood cells and are the protagonists of the adaptive immune system. After originating from blood stem cells in the bone marrow, they migrate into the thymus where they mature. ‘This lymphatic organ is basically the school where T lymphocytes learn to recognise foreign intruders,’ Höpken

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Research

18

explains. For this purpose, they are equipped with specific surface receptors, a kind of key that allows them, among other things, to dock onto infected cells. Once their development is complete, they leave the thymus as naive T cells and patrol the bloodstream and lymph nodes on the lookout for foreign antigens. They lose their ‘naivety’ at the first confronta-

also helps in the battle against cancer, because it activates cell death in stromal cells (connective tissue) and the blood vessels that feed tumours, thus destroying their basic structure. For some while, Höpken and Rehm have been examining the question of how perforin, granzymes and interferon-gamma are released from the cytotoxic T cell. Just recently, the two

tion and are thus activated as ‘armed’ effector cells. They have a vast arsenal of various regulatory and defence mechanisms at their disposal. ‘In its 7 to 14-day lifespan, a single cytotoxic T cell works extremely hard fighting approximately ten virally-infected cells,’ Armin Rehm explains. Activated cytotoxic T cells directly destroy foreign or virally-infected cells, but also tumour cells, by releasing perforin and granzymes. These will enzymatically trigger programmed cell death. In addition, they also act indirectly by releasing the protein interferon-gamma. This greatly strengthens the activity of other cells in the immune system, the macrophages, as well as the antigen presentation. Moreover, interferongamma induces the release of cytokines, which will further stimulate the immune response. Interferon-gamma

scientists decoded the role of the receptor sortilin, which is also present in nerve and liver cells, in the transport of interferon-gamma, and indirectly in the transport of granzymes. On the lock and key principle, sortilin picks molecules out of the Golgi-apparatus and puts them in transport vesicles, which travel in the direction of endosomes and lysosomes. ‘In an artificial system with knock-out mice, we’ve been able to control the down and up regulation of sortilin in the cell. If the receptor is missing, immune defence in general will suffer,’ says Rehm.

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Therapies derived from the individual cells of patients?

With experiments on the molecule EBAG9, the scientists were able to

demonstrate the potential future role of cytotoxic T cells in cancer therapy. They proved that the protein, which is regulated by the action of oestrogen, plays a vital part in the maturing and loading of transport vesicles. In an experiment they deactivated the gene for EBAG9 and observed that cytotoxic effector cells were able to release more lysosomal enzymes and thus kill tumour cells. ‘The tumour treatment of the future will be a tailored, individualised therapy in which T cells are taken from the patient, genetically modified and then returned,’ says Armin Rehm enthusiastically. Uta Höpken and Armin Rehm have been working together on joint projects since 2002. They attribute their success to the fact that they deliberately evolved in divergent directions in the past. They met in Marburg in 1988 working in the same lab on their diploma and doctoral theses, respectively. Afterwards, they went to the United States together, but intentionally chose different labs at MIT and Harvard Medical School. ‘We are very versatile today because we used to focus on different research topics and have acquired a wide variety of methods, and that greatly benefits our cooperation,’ Uta Höpken emphasises. ‘We were both lucky to have supervisors like Bernd Dörken and Martin Lipp who gave us lots of freedom to build our own groups and recruit good people,’ Armin Rehm adds. Their research will continue to focus on the basic question of how to impact and stimulate a transport channel to increase the potency of a T cell's toxicity towards tumour cells. They believe there is potential for treating tumours in the haematopoietic system, such as lymph gland cancer and leukaemia. ‘In order to achieve that, however, we first have to shed light on the highly complex transport and regulatory mechanisms in the cell,’ Uta Höpken and Armin Rehm hope.

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Esprit d‘Echange long live science A large and diverse number of cultural and scientif ic events marked last year’s celebration of the 50th anniversar y of the Franco-German Elysée Treaty; MDC scientists also played a par t

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he international prominence of French research institutions is well-recognised and it is no wonder that three French scientists have been awarded the Nobel Prize in physiology and medicine over the last five years. Germany and France enjoy strong and uniquely symmetrical educational and scientific exchange (with roughly the same number of scholars crossing the border in both directions), and MDC has profited. There are usually about 20 French scientists at MDC at any one time; a joint MDC-INSERM research group has been established (see the article on page 20 of this issue), and a long-standing cooperation between Charité, MDC and Pierre et Marie Curie University in Paris has spawned the international training group MyoGrad. In this spirit of exchange, MDC scientists co-organised two quite special bilateral scientific meetings that were supported by and held at the French Embassy in Berlin and attended by more than 120 international participants.

The 1st German-French Symposium ‘Frontiers of Cardiovascular Research: From Basic Concepts to Novel Approaches in Therapy and Prevention’ is the outcome of a number of individual exploratory visits and a few already existing fruitful collaborations. This event drew a much wider range of senior scientists from MDC, Charité, the German

Heart Institute Berlin; and five French institutions, with INSERM, the Collège de France and the Paris-Cardiovascular Research Center (PARCC) among them. Participants discussed their recent findings in a broad range of topics related to both fundamental and translational aspects of cardiovascular research. And more than 20 PhD students and post-doctoral fellows from the two countries had a unique opportunity to present their research at a lively poster session. A second meeting, ‘Perspectives of Systems Biology – from Modelling to Therapy of Complex Diseases’, drew speakers from more than ten companies and research institutions, including MDC/BIMSB, DKFZ, the MPI for Molecular Genetics, the University of Luxemburg, Institut Curie, and the École normale supérieure, who addressed themes such as “Genomes to Networks”, ‘Computational Biology’, ‘Genomics’ and ‘Epigenetics’ in relation to cancer, inflammation, as well as neurodegenerative and cardiovascular diseases. Scientific talks were complemented by presentations on national funding strategies given by Karin Effertz from the German Ministry of Education and Research (BMBF) and Jan-Michel Heard from

the French National Research Agency (ANR). Both meetings have strengthened MDC's international networks and provided an excellent platform to exchange ideas on future collaborations and funding opportunities. Oksana Seumenicht

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Source for regenerative therapies: Michael Sieweke aims at solving the "drag on growth" of mature cells.

D em ys t i f y i n g

Regeneration Franco-German friendship : in Southern France, MDC scientist Michael S ieweke and his team successf ully explore in the framework of the Hemholt z-INSERM initiative alternatives to embr yonic stem cell therapy T e x t Ma i m o n a Id

P h oto s J ea n - m a r i e H u r o n

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nce a cell has fully matured and specialised in its functions it can no longer divide, or only to a very limited extent. As a result, a body that suffers a spinal cord injury resulting in paraplegia, for example, is unable to repair severely damaged nerve cells. This ‘growth failure‘ has hitherto been one of the unsolved riddles of Regenerative Medicine. It therefore strives to heal the functions of organs or tissues impaired by acute or chronic disease by using cell replacement therapy. Scientists like Dr. Michael Sieweke face the challenge of producing a sufficient number of mature cells to fulfil the tasks of an organ as complex as the pancreas. With his team at the well-known Centre d'Immunologie de Marseille-Luminy (CIML), in Southern France, he may have solved the crucial problem of diminished growth in

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highly specialised cells. Just in time to mark the 50th anniversary of the Elysée Treaty, which sealed Franco-German cooperation and friendship in 1963, MDC now has a French connection of its own. In autumn 2012, the Max Delbrück Center for Molecular Medicine (MDC) and the French National Institute of Health and Medical Research (Inserm) launched a collaborative project in which Michael Sieweke explores the basic molecular and cellular mechanisms of regeneration at the interface of Immunology and Stem Cell Science. France and Germany are intensifying their collaboration in the area of science and health research through the Helmholtz-INSERM initiative, which provides funding for cooperating scientific groups. Up until now, the source for developing regenerative therapies were

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embryonic or adult stem cells because of their ability to reproduce infinitely and to produce various of the cell types in the body – the former subject to ethical controversy, and the latter unsuitable for isolation in sufficient numbers. Induced pluripotent stem cells (iPSC) are the current ‘state of the art’ in Stem Cell Research. These are stem cells which are genetically reprogrammed from fully differentiated cells in the body, such as skin cells, to assume their original state. Theoretically, this makes them able to reproduce and then develop into any desired cell. ‘The advantage: you don’t have to use embryos for research. The drawback: it’s a very elaborate and complex detour to reprogramme, reproduce, and then specialise the cells,’ Michael Sieweke explains. This is precisely what the scientist wants to avoid.

‘Ultimately, what I need to heal a disease are specialised cells with a precisely defined function. Our research goal is to skip the stem cell step and reproduce fully matured cells right there in the Petri dish,’ Sieweke says. He has already managed this with macrophages, the phagocytes, which are the focus of his work. Macrophages – more than just ‘big eaters’

Macrophages are white blood cells and can be found almost anywhere in the body. They fulfil numerous tasks in the body's immune defence, one of which is the destruction of pathogens such as bacteria or viruses. In this process, called phagocytosis, cells ingest and digest pathogens – hence their name, which is Greek for ‘big eaters’.

Michael Sieweke is interested in one function in particular. ‘Depending on their state of activation, macrophages cause either inflammatory or regenerative processes. In many chronic or acute inflammatory conditions, such as a heart attack, they assume an important control function,’ he explains. The scientist wants to shed light on this mechanism, as well as cell development from their precursor cells, the hematopoietic stem cells. In order to do this, he analysed a group of regulatory control molecules from the Maf family. The proteins, called transcription factors, play a role in gene expression. They are highly active in macrophages. ‘We thought that their primary purpose was to maintain the special functions of the differentiated cell,’ Sieweke explains. Using a knockout model, researchers deactivated

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’‘MDC's outpost in France: Michael Sieweke (middle) and his research group at the Centre D'Immunologie de Marseille-Luminy (CIML).

‘We researchers are modern nomads.’

the relevant factors at the genetic level. To their great surprise, the mature macrophages suddenly began to divide and amplify. Contrary to expectations, they also maintained their state of differentiation. Infinite growth, but not uncontrolled proliferation

Since then, macrophages have been growing in cell cultures for more than two years. Besides embryonic stem cells only tumour cell lines have the same infinite life expectancy. ‘We used various tests to rule out the possibility that genetically modified macrophages in mice could develop carcinogenic potential,’ the stem cell researcher emphasises. After the genetically modified cells had been transplanted back into the organism, they resumed their normal functions such as phagocytosis. ‘If our research results can be applied to other cell models, it would be a minor revolution in stem cell research,’ Sieweke explains. A virtually unlimited supply of fresh, potent cells would be within our reach. Dr. Sieweke is thrilled about his collaboration with MDC. ‘I think of our group as a little MDC outpost. We benefit enormously from the scientific expertise and outstanding technological platforms in Berlin-Buch,’ he is happy to report. But he also enjoys

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the excellent environment at a leading immunology institute and his workplace in one of Europe’s most beautiful natural parks directly on the Mediterranean. When asked why he went to France , he smiles. ‘You’re not asking me quite the right question. I didn’t so much go to France as stay in Europe,’ he emphasises. A German national, French resident by choice and a professed European, it is important to him that excellent scientists do not all drift off to the Anglo-American research area, but also perceive France as a powerful research nation. Even though science and nomadism do not seem to have much in common at first sight, Michael Sieweke claims, ‘We

Still operational: Genetically modified macrophages in the digestive process of bacteria (green).

researchers are modern nomads.’ After Tübingen, Berkeley (USA), Heidelberg and Melbourne (Australia) the scientist has now made a home for himself and his family in Marseille, where he has lived and worked for the last thirteen years. Something else shared by researchers and nomads is freedom – the freedom to think independently, without which discoveries like Michael Sieweke’s would not be possible. http://www.ciml.univ-mrs.fr/fr/ science/lab-michael-sieweke/ pour-les-experts

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Highlight Paper Neural precursor cells (brown) from the brain of a transgenic mouse form several layers around the mass of a brain tumor (red). The precursor cells release tumor-suppressing substances called endovanilloids, which stimulate a receptor on the surface of the tumor cells and cause them to undergo apoptosis. Neural precursor cells circulate widely in young brains, but their tumor-suppressing effects are lost and brain cancer spreads much faster as a patient gets older. The image shows a region of the brain where stem cells and precursor cells naturally occur. This niche, called the subventricular zone, is located in structures called ventricles that hold brain fluids (depicted at the bottom left of the picture).

New Target in the battle against deadly Brain tumors MDC scientists discover factors that cause tumor cell death Tex t Russ Hodge

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P h oto Ra i n e r G l a s s u n d M i c h ae l Sy n ow i t z

utations that could potentially cause cancer happen all the time in our cells, but many seem to be blocked by natural defenses against the disease. These protective mechanisms might provide a starting point for the development of potent new therapies; unfortunately, they have been elusive. But a new study from Helmut Kettenmann's group at the MDC reveals a mechanism that helps the body fight one of the deadliest forms of brain cancer: high-grade astrocytoma (HGA). Rainer Glass, a former postdoctoral fellow in Helmut's lab (and now professor at the University of Munich, LMU), and his colleagues show that stem cells in the brain called neuronal precursor cells (NPCs) are attracted to HGA cells. When they draw near, they release factors that cause the tumor cells to self-destruct. The study,

published in the August edition of Nature Medicine, suggests a completely new approach toward a disease that has stubbornly resisted treatment and is nearly always fatal. ‘High-grade gliomas are a type of cancer with an extremely poor prognosis,’ Helmut says. ‘A patient's average survival time after diagnosis is typically about a year and there are almost no five-year survivors. Moreover, there has been essentially no progress in finding cures over the past 30 years, despite attempts to treat HGAs with radiotherapy, chemotherapy, and surgery.’. For many years Helmut's group and other labs have observed that neural precursor cells (NPCs) are attracted to tumor cells during the development of HGAs. Researchers suspected that NPCs release factors that cause the tumor cells to die. But no one knew precisely

which factors were released, or how they affected the tumors. Endovanilloids trigger a self-destruct signal

Some of those questions have been clarified in a study by Rainer Glaß, Kristin Stock, Michael Synowitz, Jitender Kumar, and other members of Helmut's group. The scientists demonstrated that NPCs release specific fat molecules called endovanilloids. These molecules dock onto a protein called TRVP1, which appears in high quantities on the surfaces of tumor cells. The endovanilloids then activate a signal in the target cell that causes it to die. ‘What we've known about TRVP1 comes from a completely different context – it's found in the nerves that sense pain,’ Helmut says. ‘It is activated

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by capsaicin, the active component in hot chili peppers. But until now it has not been considered a player in glioma biology.’ Why don't adults enjoy the protection of endovanilloids? One factor might be a natural drop in the number of NPCs as a person ages – they are primarily needed as the brain grows and matures in infants and children. Their presence and functions in the adult brain have yet to be established. But even without them, Helmut says, it may be possible to imitate the way they affect TRVP1 and tumor growth. Discovering this mechanism required experiments ranging from the test tube to mice and an investigation of tissues obtained from human cancer patients. First, the scientists exposed tumor cells grown in lab cultures to a mixture of molecules released by NPCs.

This method allowed them to home in on endovanilloids; other molecules released by the cells didn't have anti-tumor effects. It also revealed what happens when endovanilloids dock onto TRVP1: they trigger a self-destruct mechanism in the tumor cells. Encounters between external molecules and cellular receptors like TRVP1 often set off a cascade of chemical signaling within the cell. Information is passed from one molecule to the next, eventually leading to the activation of new genes. In this case, the study established that the message is received and then passed along by a protein called ATF3 which changes the cell's pattern of gene activation. This tells the cancer cell that something is wrong and it should self-destruct.

Highlight Papers of the MDC are publications, that have an impact factor of more than 10 and where MDC scientists are first, senior or corresponding authors. 2013|01 (90)Yttrium-ibritumomab-tiuxetan as first-line treatment for follicular lymphoma: 30 months of follow-up data from an international multicenter phase II clinical trial. Scholz, C.W. and Pinto, A. and Linkesch, W. and Linden, O. and Viardot, A. and Keller, U. and Hess, G. and Lastoria, S. and Lerch, K. and Frigeri, F. and Arcamone, M. and Stroux, A. and Frericks, B. and Pott, C. and Pezzutto, A. Journal of Clinical Oncology 31 (3): 308-313. 20 January 2013

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A new handle on deadly gliomas?

The scientists also discovered that the endovanilloids trigger a biochemical mechanism called the endoplasmic reticulum-stress pathway. The endoplasmic reticulum (ER) is a labyrinthine structure in cells made of membranes which plays an important role in the production of new proteins. Defects in the ER may cause it to accumulate enormous amounts of molecules and retain them, instead of releasing them. The structure swells up and eventually the cell dies. Under the electron microscope, the scientists observed such bloated ER structures in tumor cells from the tissues of humans, mice, and rats. Studies in the test tube and mice showed that blocking endovanilloids

T. and Lokki, A.I. and Ekholm, E. and Laivuori, H. and Gauster, M. and Huppertz, B. and Sugulle, M. and Ryan, M.J. and Novotny, S. and Brewer, J. and Park, J.K. and Kacik, M. and Hoyer, J. and Verlohren, S. and Wallukat, G. and Rothe, M. and Luft, F.C. and Muller, D.N. and Schunck, W.H. and Staff, A.C. and Dechend, R. Circulation 126 (25): 2990-2999. 18 December 2012

Microglia: new roles for the synaptic stripper. Kettenmann, H. and Kirchhoff, F. and Verkhratsky, A. Neuron 77 (1): 10-18. 09 January 2013

2012|11 The sorting receptor sortilin exhibits a dual function in exocytic trafficking of interferon-{gamma} and granzyme A in T cells. Herda, S. and Raczkowski, F. and Mittruecker, H.W. and Willimsky, G. and Gerlach, K. and Kuehl, A.A. and Breiderhoff, T. and Willnow, T.E. and Doerken, B. and Hoepken, U.E. and Rehm, A. Immunity 37 (5): 854-866. 16 November 2012

Genomic variation landscape of the human gut microbiome. Schloissnig, S. and Arumugam, M. and Sunagawa, S. and Mitreva, M. and Tap, J. and Zhu, A. and Waller, A. and Mende, D.R. and Kultima, J.R. and Martin, J. and Kota, K. and Sunyaev, S.R. and Weinstock, G.M. and Bork, P. Nature 493 (7430): 45-50. 03 January 2013

A misplaced lncRNA causes brachydactyly in humans. Maass, P.G. and Rump, A. and Schulz, H. and Stricker, S. and Schulze, L. and Platzer, K. and Aydin, A. and Tinschert, S. and Goldring, M.B. and Luft, F.C. and Baehring, S Journal of Clinical Investigation 122 (11): 3990-4002. 01 November 2012

2012|12 CYP2J2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia. Herse, F. and LaMarca, B. and Hubel, C.A. and Kaartokallio,

The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers. Calado, D.P. and Sasaki, Y. and Godinho, S.A. and Pellerin, A. and Koechert, K. and Sleckman, B.P. and de Alboran,

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removed the anti-tumor effects of the stem cells. This could be done either by breaking down the fat molecules themselves, by removing TRPV1 from the tumor cells, or blocking the signal that was generated by their interaction. In all of these cases, the cells failed to receive a signal to die, and even the presence of NPCs failed to protect an organism from aggressive tumors. ‘This has important implications for the development of new therapies against high-grade gliomas,’ Helmut says. ‘When we treated older mice with artificial endovanilloids, they responded like young mice. Even when these mice had low numbers of NPCs, we saw an increase in the biochemical pathway stimulated by TRPV1 and a significant increase in the animals' survival.’ Previous work on TRPV1 in its other context – pain reception – had

identified a drug called Arvanil that activates the receptor. When the scientists applied it to mice with aggressive gliomas, the drug strongly reduced tumor growth. ‘While Arvanil can't be used in humans due to side effects,’ Helmut says, "the studies in mice establish a proof of principle. Namely, that it makes sense to develop and test novel agents that activate TRPV1. They might become a crucial new tool in fighting a type of tumor that has been resistant to all the options for treatment that are currently available.’

References: Kristin Stock*, Jitender Kumar*, Michael Synowitz*, Stefania Petrosino, Roberta Imperatore, Ewan St J Smith*, Peter Wend*, Bettina Purfürst*, Ulrike A Nuber, Ulf Gurok, Vitali Matyash*, Joo-Hee Wälzlein*, Sridhar R Chirasani*, Gunnar Dittmar*, Benjamin F Cravatt, Stefan Momma, Gary R Lewin*, Alessia Ligresti, Luciano De Petrocellis, Luigia Cristino, Vincenzo Di Marzo, Helmut Kettenmann* & Rainer Glass*. Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1. Nature Medicine (2012), Vol. 18 No. 8, August 2012, 1232-1239. *) MDC-scientists

Latest Highlight Papers

I.M. and Janz, M. and Rodig, S. and Rajewsky, K. Nature Immunology 13 (11): 1092-1100. November 2012 2012|10 Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. Kaji, T. and Ishige, A. and Hikida, M. and Taka, J. and Hijikata, A. and Kubo, M. and Nagashima, T. and Takahashi, Y. and Kurosaki, T. and Okada, M. and Ohara, O. and Rajewsky, K. and Takemori, T. Journal of Experimental Medicine 209 (11): 2079-2097. 22 October 2012 Chloride in vesicular trafficking and function. Stauber, T. and Jentsch, T.J. Annual Review of Physiology 17 October 2012 (In Press) 2012|09 Colonization of the satellite cell niche by skeletal muscle progenitor cells depends on notch signals. Broehl, D. and Vasyutina, E. and Czajkowski, M.T. and Griger, J. and Rassek, C. and Rahn, H.P. and Purfuerst, B. and Wende, H. and Birchmeier, C. Developmental Cell 23 (3): 469-481. 11 September 2012 Krueppel-like factor 15 regulates Wnt/beta-catenin transcription and controls cardiac progenitor cell fate in the postnatal heart.

Noack, C. and Zafiriou, M.P. and Schaeffer, H.J. and Renger, A. and Pavlova, E. and Dietz, R. and Zimmermann, W.H. and Bergmann, M.W. and Zelarayan, L.C. EMBO Molecular Medicine 4 (9): 992-1007. September 2012 2012|08 Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis. Sander, S. and Calado, D.P. and Srinivasan, L. and Koechert, K. and Zhang, B. and Rosolowski, M. and Rodig, S.J. and Holzmann, K. and Stilgenbauer, S. and Siebert, R. and Bullinger, L. and Rajewsky, K. Cancer Cell 22 (2): 167-179. 14 August 2012 Editorial authors‘ reply to Freedhoff. Floegel, A. and Pischon, T.v British Medical Journal 345 : e5109. 06 August 2012 Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin. Rosario, M. and Schuster, S. and Juettner, R. and Parthasarathy, S. and Tarabykin, V. and Birchmeier, W. Genes & Development 26 (15): 1743-1757. 01 August 2012

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The Case of the Short-fingered Musketeer Russ Hodge

Photography: Maj Britt Hansen · Philipp Maass · Hakan Toka

The Case of the Short-fingered Musketeer by Russ Hodge

Afterwords by Friedrich C. Luft and Nihat Bilginturan

Book pr es en tat i o n

The Case of the Short-fingered Musketeer A biomedical adventure spanning 20 years of research at MDC Te x t Rus s Hodge

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Ph otos Ma J Brit t H A nse n, Philipp Maas s, Haka n Toka

hen I arrived at MDC six years have predicted it: over two decades the reach middle age, the blood vessels in ago, I began writing a book project has pulled in dozens of resear- their brains can no longer withstand called ‘Translations’ that told 25 stories chers, all of whom claim that it has had the pressure, and they die of strokes. about scientific work going on across a profound influence on their lives and Fifty years ago, the religious leathe campus. In the process, I came ac- careers. der of the community – also affected ross a project that had begun as one of by the disease – noticed a connection the first at MDC and was still going on. In Northern Turkey, on the coast between the short fingers and sudden I first heard the story that would evolve of the Black Sea, lives a family of far- death among his relatives, and sought into ‘The Case of help. Finally, in In Northern Turkey, on the coast of the Black the Short-finge1970, he found a Sea, lives a family of farmers with a unique red Musketeer’ in doctor named Nihereditar y condition. the office of Fred hat Bilginturan Luft, over in the old Franz-Volhard Cli- mers with a unique hereditary condi- who came to the village, made a careful nic. At the time, I had no idea that the tion. Those who are affected have un- pedigree of the family, and published a project had so many different facets, usually short fingers and toes – which paper on the syndrome. It languished that it would become a sort of personal is trivial – but also blood pressure va- in the literature for twenty more years adventure, or that I would spend nearly lues that rise and rise until they reach until it was discovered by a human getwo years writing about it. Fred might astronomical heights. By the time they neticist named Thomas Wienker, while

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preparing a talk to be given at the newly established MDC. From a unique case to general principles of a deadly disease?

Fred Luft had just been hired by Detlev Ganten as one of MDC's first researchers, and he decided to follow up on the story as one of the first scientific projects of the new institute. Fred and his colleagues have been working on the case ever since. Why so much effort on a case that affects so few people? One reason lies in the fact that the family's syndrome seems to resemble essential hypertension – a type of high blood pressure that affects about a quarter of the world's population and whose causes are unknown. ‘We know that there is usually a genetic component to major diseases such as hypertension,’ Fred says. ‘But these conditions usually involve subtle interactions between many genes, making them tremendously hard to find. Our hope is that such unusual cases caused by single genes will point to culprits that may be defective in the population as a whole.’ Uncovering the cause of the family's problem has required applying nearly every new concept and technology that has arisen in biology over the last 20 years, making the case a sort of parable for modern biomedicine. The story points out the enormous difficulty of pursuing ‘molecular medicine’ when starting with human patients and working your way toward a disease mechanism. Most of our projects begin the other way around, when a lab focusing on a gene or a cellular mechanism discovers a new link to disease. ‘The Case of the Short-fingered Musketeer’ tells the story of this scientific project and much more. It has been a cultural adventure as well as a scientific one. The first step in launching the project was to find the Turkish family, which turned out to be more difficult

than anticipated. First Fred and his colleagues had to find Nihat Bilginturan and get him to agree to collaborate by introducing them to the family. Fortunately, Herbert Schuster, another of MDC's first group leaders, had a young Turkish-German doctor in his group who could fly to Turkey and speak to Bilginturan directly. Hakan Toka managed to convince the elderly doctor to participate, and the team flew over to meet the family. Later, Hakan's brother, Okan Toka, would spend a year living with them, carrying out a drug trial to try to find a treatment to get their blood pressure under control. Through red tape and gunfire : when scientists and their subjects become friends

Ever since, the family in Turkey has played an active role in the research, submitting to endless poking and prodding, extended stays in hospitals in Turkey and Berlin for tests, and repeated visits by the scientists. The researchers have encountered numerous problems along the way due to the difficulties of carrying out research on human patients across international borders. Just getting permission to travel

to Turkey to take blood samples has often required months of letter-writing to navigate the red tape. Doing the research for this book required that I make two trips to Turkey with Fred and his team, including a week spent with the family and another visit to meet Nihat Bilginturan. Over the following two years, interviews with the scientists brought out details of the story including bizarre coincidences and hilarious anecdotes. When Bilginturan first visited the family, the roads were so poor that he had to carry his scientific equipment up to their village on the backs of two mules. The title was inspired by an incident in which one of Okan Toka's patients fired off a gun and was thrown in jail, requiring the young doctor to meet with lawyers and a judge to save the old man's life. At one point the team traveled to South Africa in hopes of finding another family that suffered from the disease. It turned out the family didn't have the same problem – but along the way they met another doctor with a patient who did Scientifically, the story provides deep insights into the factors that have motivated Sylvia Bähring, Atakan Aydin, Philipp Maass, and other members of the team to pursue a project over two decades. That work has often

Research under difficult conditions: On the spot, scientist Sylvia Bähring ensures the reliability in taking patient ‘s samples.

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Just published Musketeer Ali B.: Thanks to him and his family, the German-Turkish researchers’ team has made a major step to come closer to the causes of high blood pressure.

The Case of the Shortfingered Musketeer by Russ Hodge 2013, published by the Max Delbrück Centre for Molecular Medicine

been frustrating, but also rewarding: now the project seems to have exposed a new mechanism by which the information in our DNA can lead to disease. Writing the book drew in everyone who has been involved in the project over the past 20 years – scientists, physicians, a neurosurgeon, and, of course, the family in Turkey. We were fortunate to have two excellent photographers along on the trip – Maj Britt Hansen and Philipp Maass. Hakan Toka provided photographs from all of the early trips. Nicola Graf, who designed ‘Translations’, came up with an original design that reflects the adventure we all experienced. A wonderful artist and an old friend from the U.S., Stephen Johnson, provided a brilliant cover. The book includes an afterword by Nihat Bilginturan, one of the most colorful characters I have ever encountered, and a second by Fred Luft, another colorful character, who explores the important issue of non-hypothesis-driven research. I have tried to bring the tools of a novelist to the story of one of the most interesting and unusual projects that has been carried out at our institute – and likely anywhere else. This style aims to give the widest possible audience insights into the personalities and the science that underlie molecular medicine. Please judge the results for yourself.

The Case of the Short-fingered Musketeer tells the story of an MDC project which turned into a unique, decade-spanning adventure in biomedical research. Scientist Fred Luft and colleagues have been investigating an unusual hereditary disease suffered by a family in Turkey for the last 20 years. The genetic defect produces shortened fingers and toes as well as extremely high blood-pressure (more on p. 26-28). To obtain a copy of the book, contact Michaela Langer, House 84, Room 1001/1002 in the Communications Department at the Max Delbrück Center for Molecular Medicine, Email: [email protected] Special edition bild der wissenschaft plus ‘Gesundheit 2030 – Die molekulare Herausforderung’ January 2013, Verlag Konradin Medien GmbH

From basic research to applications – this special issue offers some exciting insights into the scientific activities of the Max Delbrück Center. With a print run of 80,000, readers across Germany can learn all about the most recent results produced by MDC researchers and the challenges they pose for biomedicine. This special issue can be obtained from the Communications Department at MDC, House 84, Room 1011. Email: communications@ mdc-berlin.de plus

GESUNDHEIT

2030

Die molekulare Herausforderung

Eine Sonderpublikation in Zusammenarbeit mit dem Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch und dem Leibniz-Institut für Molekulare Pharmakologie

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Of Mice and Mode ls

Molecular Genetics or Systems Biology – how can we understand the complexities of Biomedicine? Every year, scientists of various disciplines gather at the ‘Berlin Summer Meeting’ to explore these questions T e x t A l exa n de r L o ewe r

P h oto s l e n a vo n o e r t ze n

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or decades, geneticists have been developing ever more sophisticated methods to modify the genetic make-up of selected model organisms and to infer the function of the examined genes from the changes they observe. However, this can only be done gene by gene, and every added modification will lead to complex changes in the organism. This is where Systems Biology comes in, which analyses biological systems holistically: Each molecular reaction in the cell is considered part of a tightlywoven network. In order to make this approach work, Systems Biologists

combine high-throughput experimentation with computer-based as well as theoretical analysis. Under the slogan, "Experimental and Computational Biology MEET", scientists of various disciplines gather each year at the Berlin Summer Meeting. Nikolaus Rajewsky, Scientific Coordinator of the Berlin Institute for Medical Systems Biology (BIMSB) at the Max Delbrück Center (MDC) established this interdisciplinary conference in 2008 in order to discuss basic themes of Systems Biology with internationally renowned experimental and computational biologists. In 2012, the conference

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Idyllic nature on Döllnsee: Markus Landthaler of BIMSB (right) and Fabio Piano from New York University (NYU) use the quiet environment for detailed discussions.

Researchers from various disciplines discuss the challenges of biomedicine during the ‘Berlin Summer Meeting’.

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was given a special, particularly focused format: Klaus and Nikolaus Rajewsky invited a number of excellent scientists from around the globe to a three-day retreat with MDC researchers at Döllnsee in the Schorfheide, which is north of Berlin. The goal was to contrast two scientific approaches, which each in its own right, or in combination, promises a deeper understanding of the complexity of living organisms: Genetics and Systems Biology MDC, named after Max Delbrück, one of the founders of modern Genetics, is internationally renowned for its expertise in Molecular Genetics. Many of its sixty working groups use the Molecular Genetics approach to research the origins of human disease. At the

same time, MDC also promotes Systems Biology by making new appointments and providing high-throughput technologies. Ten groups have already been established at the BIMSB, among them three technology platforms. This makes MDC an excellent venue for Geneticists and Systems Biologists to cooperate and combine their strengths. One example to illustrate this approach: microRNAs are short sections of genetic information with a great impact on cellular behaviour, as every

microRNA has the potential to influence the activity of thousands of other molecules. Geneticists are now examining the significance of regulating all these predicted targets. Often it turns out that influencing just a few target genes suffices to explain the impact of microRNAs. Why, then, are there so many different target genes? And what is the significance of regulating these target genes? These and many other questions were discussed intensely during the three days on Lake Dölln. International guests such as Fabio Piano (New York University), Neal Copeland (MHR Institute Houston) and Steve Cohen (IMCB Singapore), as well as MDC group leaders and scientists from all over Germany, reported on their results. It soon became clear that, already today, there are no longer any clear boundaries between Systems Biology and Genetics. Rather, the two approaches must be linked closely in order to answer the complex questions of modern Biomedicine. Promoting interdisciplinary cooperation will be the key to making Biology, Physics and Mathematics converge. And training young scientists will be the foundation for such a synergy. MDC provides an ideal environment for this, as it combines outstanding expertise in Molecular Medicine with strong, expanding Systems Biology, thus facilitating molecular basic research whilst making translational progress, too.

Research

The immune sys te m : a pa r tne r i n t h e fig h t ag a in s t ca nce r The immune system protects the body from pathogens like viruses and bacteria. But does it also help to combat cancer? At MDC’s Cancer Day on 14 November, 2012, doctors and cancer researchers from Charité and MDC shared ideas with the main speaker, Guido Kroemer, Director of the Institute Gustave Roussy at the National Institute of Health and Medical Research (INSERM).

Time for young researchers: The renowned scientist Guido Kroemer discusses the work of the PHD student, Chris Fröhlich.

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hen healthy cells mutate into cancer cells the number of sets of chromosomes set is often increased. Upon which, degenerated cells activate a stress programme and express the protein calreticulin on their surface. Utilizing mouse model systems, Guido Kroemer and his team have demonstrated that the immune system is able to remove cancer cells expressing calreticulin. However, the cancer cells frequently manage to escape the immune defence by reducing the number of chromosomes and thus shutting down the stress reaction and the calreticulin expression. This protects the cancer cells and allows unhindered tumour development. Treatment often involves chemotherapy which targets and kills the cancer cells. Guido Kroemer and his team are investigating whether the immune system plays a supporting role in

this therapy. Using microscopic video analysis they tested 980 different active ingredients and have shown that certain anticancer therapeutics activate the immune system which then itself destroys cancer cells. To their surprise they discovered that drugs that are used to treat heart conditions, like digoxin, also activate the immune system. The plan is now to test a combination of chemotherapy and digoxin on patients with so-called head and neck cancer. Kroemer’s work has managed to elucidate the synergetic link between chemotherapy and the immune system. ’The next thing we have to do is analyse how the immune system’s fight against the tumour works on the molecular biological level‘, say Guido Kroemer. Michael Hinz

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News

Influenza viruses in the immediate vicinity of a host cell. | Image: Kai Ludwig © Humboldt-Universität zu Berlin

Systematically fighting the flu virus

In the new Berlin collaborative project “ViroSign – Systems Virology of Influenza – the molecular signature of permissive virus infection”, MDC researcher Professor Dr. Matthias Selbach and his colleagues at the Integrative Research Institute for the Life Sciences (IRI) at Humboldt-Universität zu Berlin (Professor Dr. Dr. h.c. Edda Klipp, Professor Dr. Andreas Herrmann), the Max Planck Institute for Infection Biology (Professor Dr. Thomas Meyer) and the Robert Koch Institute Berlin (Associate Professor Dr. Thorsten Wolff), explore which factors determine a – from the virus’ point of view – successful infection. Their goal is to characterise the typical protein signatures (proteome) of a host cell and, as comprehensively as possible, the temporal dynamics of all interconnected virus-host cell interactions after infection by an influenza virus. The Federal Ministry of Education and Research (BMBF) provides the research network with funding totalling 1.94 million euro under the e:Bio Programme. Newly discovered risk factor for high blood-pressure during pregnancy offers therapy approach

Pre-eclampsia, a serious complication during pregnancy, is one of the Pr e s s

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leading causes of maternal and infant mortality in Europe and the U.S. It affects approximately one in every twenty pregnancies. The main symptoms are high blood-pressure and protein in the urine. The question as to what causes pre-eclampsia remains unanswered. Dr. Florian Herse (Experimental and Clinical Research Center (ECRC) at MDC and Charité) and Dr. Ralf Dechend (ECRC and Helios Clinic Berlin) have now discovered an enzyme that occurs more frequently in the women affected and appears to be involved in the symptomatology. They blocked the enzyme in an animal experiment and were able to alleviate the progression of the disease CYP2J2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia: 10.1161/ ​C IRCULATIONAHA.112.127340

scientific journal Genes and Development. Both scientists work in the research group of Professor Clemens Schmitt, who heads a group at MDC and works as an Oncologist at Charité’s Virchow Clinic. Doctoral candidate in Biology, Hua Jing, physician Dr. Kase and Clemens Schmitt are researching a cell protection programme, known as senescence, which can impede the growth of cancer cells. While doing so, they discovered that the genetic switch, NFkappaB, which is thought to promote cancer development in various forms of lymphoma and is partly responsible for a tumour no longer responding to treatment, also has a good side: ‘This switch reinforces the senescence triggered by chemotherapy, which completely stops cell division in lymphoma,’ Prof. Schmitt explained.

Hua Jing | Photo: David Ausserhofer | © MDC Dr. Julia Kase | Photo: Dietmar Spolert

Chemist Professor Michael Glickman of Technion – the Israel Institute of Technology in Haifa.

Curt Meyer Memorial Prize for MDC and Charité researchers: genetic switch plays a contradictory role in cancer

Bessel Research Award for Michael Glickman of Technion : close collaboration with Max Delbrück Center

Cancer researchers Hua Jing of Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Dr. Julia Kase of Charité – Universitätsmedizin Berlin were awarded the 2012 Curt Meyer Memorial Prize on 18 December 2012. The President of the Berlin Cancer Society, Professor Peter M. Schlag (Charité, MDC) conferred the award, which is endowed with a total of 10,000 euro, for a study that appeared in the U.S.

Chemist Professor Michael Glickman of Technion, the Israel Institute of Technology in Haifa, has been granted the Friedrich Wilhelm Bessel Research Award for his outstanding research achievements by the Alexander von Humboldt Foundation. Glickmann will use the 45,000 euro-award to intensify his long-standing cooperation with Cell Biologist Professor Thomas Sommer at Max Delbrück Center

www.mdc -be r lin.de / de / news / 2013 / index .h tml

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for Molecular Medicine (MDC) Berlin-Buch, and will also conduct research at MDC. He will receive the award in the spring. Michael Glickman investigates a cell system in yeast cells that breaks down proteins in a controlled manner. It uses the protein ubiquitin to put a ’molecular stamp‘ on proteins that are no longer needed or faulty, which are then disposed of in the cell’s ’shredder‘, the proteasome.

Dr. Marina Chekulaeva

Dr. Marina Chekulaeva came to MDC in October 2012 as the new head of the BIMSB-group ‘Non-coding RNAs and mechanisms of cytoplasmic gene regulation’. Marina Chekulaeva did her PhD at EMBL, Heidelberg with Dr. Anne Ephrussi, where she studied how mRNA transport is coupled with translational regulation. For her postdoc, she joined the labs of Dr. Witek Filipowicz (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland) and Dr. Roy Parker (University of Arizona in Tucson, USA) to study the mechanisms of miRNA function. The Chekulaeva lab focuses on understanding the molecular mechanisms that regulate mRNA translation, localisation and stability, and the role of non-coding RNAs in this process.

Professor Uwe Ohler

Professor Uwe Ohler, new BIMSB group leader working on “Computational Regulatory Genomics”, joined MDC in September 2012. Arriving from Duke University Medical School, Durham, North Carolina where he was Assistant Professor (2005-2011) and Associate

Professor (since 2011) of Computational Biology, his move to Berlin also came with a full Professorship in the Department of Biology at HumboldtUniversität zu Berlin. Uwe Ohler’s group develops mainly computational methods to identify which regions in the genome and transcriptome are responsible for expressing genes when and where they are needed. The goal is to decipher the “regulatory code”, that is, how these precise gene expression patterns are encoded in DNA and RNA, and which changes in the code are related to diseases.

Dr. Baris Tursun

Another new group leader at MDC is Dr. Baris Tursun. Arriving in February 2012, he and his BIMSB research group work on “Gene regulation and cell fate decision in C. elegans”. Baris Tursun did his PhD with Dr. Ingolf Bach at the Center for Molecular Neurobiology Hamburg (ZMNH) where he studied ubiquitin ligase activity during neural development. As a postdoc he followed Dr. Bach to the University of Massachusetts Amherst (UMASS, Worcester, USA) where he studied protein degradations in neurons. From 2006 until 2012, Baris Tursun worked in the lab of Dr. Hobert (Columbia University, New York), focusing on neuronal reprogramming and epigenetic regulation of cell fate conversion.

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Winners of the 2012 Image Contest Deadline for the nex t round of the competition is Thursday, 2nd May 2013.

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t the New Year's reception on the Berlin-Buch Campus, three scientific images won prizes in the 2012 Best Scientific Image Contest. First place went to Professor Dr. Jochen Meier, head of the research group on RNA Editing and Hyperexcitability Disorders. Matthias Sury and Erik McShane from Professor Dr. Matthias Selbach's research group (Cell Signalling and Mass Spectrometry) came in second place, and Gwendolyn Billig from Professor Dr. Thomas Jentsch's research group (Physiology and Pathology of Ion Transport) came third. All the winners were delighted to receive new cameras courtesy of sponsor Nikon. Each year, MDC employees are asked to submit scientific photographs they have taken of their work. The deadline for the next round of the competition is Thursday, 2nd May 2013. Visitors choose their favourite images during ‘Science Night’, a night of city-wide open-house events at scientific institutions. The competition is supported by the Society of Friends of MDC.

First Prize Neural circuits

Second Prize The flower meadow of mass spectrometry

Third Prize Looking up a mouse’s nose

Rather like the electric circuits in a computer, our neural networks perform amazing tasks which, however, far exceed the capabilities of a computer. Purple indicates the nerve cells which have been stimulated by gene transfer to produce therapeutically effective proteins. The dendritic tree, where the incoming signals converge, appears in blue, and yellow identifies the cell cores.

If painter Claude Monet were alive today, he would surely relish the image produced by a mass spectrometer. The coloured “flowers” show protein fragments of the intestinal bacterium Escherichia coli. They were analysed with the help of a mass spectrometer, which works like high-precision scales, identif ying protein fragments by their exact weight. A state-of-the-art mass spectrometer facilitates the analysis of hundreds of proteins in just a few hours.

The image shows a cross-section of the nasal cavity of a mouse in which various structures have been marked with fluorescent dyes. You can see the nasal concha covered with olfactory mucosa. It contains innumerable olfactory receptor neurons from which tiny sensory cilia protrude into the nasal cavity (in yellow). Here is where odorants are detected and translated into neuronal signals. The red structures are the axons of the olfactory cells which bundle together in large clusters under the mucosa and transmit the olfactory signal to the brain. Every cell can be recognised by its blue core.

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insight s Cutting the cake on the 20th anniversary of the Max Delbrück Center (MDC) on 7 December 2012: (from lef t) Prof. Walter Rosenthal (Chair of the Board and Scientific Director), (former) Federal Minister of Research, Prof. Annette Schavan, Cornelia Lanz (Administrative Director, MDC), Prof. Ulrich Frei (Medical Director, Charité) and Prof. Annette Grüters-Kieslich (Dean of Charité).

Congr atulations

MDC

The Ma x Delbrück Center for Molecular Medicine ( MDC) celebrated its 20th anniversar y. Friends and a ssociates expressed their congratulations. P h oto s Dav i d Au s s e r h o f e r

More than 400 guests from science, politics and the public followed the invitation to the 20-year anniversary celebration.

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< Professor Annette Grüters-Kieslich, Dean of Charité: ‘By founding BIH as a model institution we are opening up a one-off opportunity for translational research. This is a crucial step forward in the campaign to overcome segregation into university and non-university research.’

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bly assisted by MDC Board Chairman, Professor Walter Rosenthal, and Administrative Director, Cornelia Lanz, (former) Federal Minister of Research, Professor Annette Schavan, having held her official speech, then proceeded to cut the three-tiered birthday cake. At a ceremony entitled ‘Research and Responsibility’ on 7 December 2012, MDC celebrated its 20th anniversary. Politics and academia were well-represented, including Berlin’s Senator for Economics, Technology and Research, Cornelia Yzer, the Vice President of the Berlin House of Representatives, Anja Schillhaneck, and Professor Dr. Jürgen Mlynek, President of the Helmholtz Association to which MDC belongs. In his speech, Walter Rosenthal recognised the achievements of the founding director, Professor Detlev Ganten, and his successor, Professor Walter Birchmeier, whose appointments policy and excellent scientific work paved the way for MDC’s enormous success. Looking to the future and the upcoming establishment of the Berlin Institute of Health as a common umbrella for Charité and MDC, Professor Walter Rosenthal said ‘This is a unique chance for MDC and Charité to put their common translational activities on a new footing, both in terms of content and structure.’

‘Research and Responsibility’: Postdoc Gwendolyn Billig, scientific director Walter Rosenthal, moderator Heike Schmoll from FAZ, founding director Detlef Ganten and PhD student Nuria Cerdá-Esteban debated on stage (from left to right)

A happy reunion: Wolf-Michael Catenhusen (former State Secretary), Konrad Buschbeck (former advisor and member of the Board of Trustees and the Scientific Board of the MDC) and Jan Grapentin (Federal Ministry of Education and Research).

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< Professor Jürgen Zöllner, E xe c u ti ve D i re c to r of th e Ch a r i té Fo u n d ati o n : ‘I hope that MDC’s success will increase exponentially and that ‘BIH’ will be infinitely greater than the sum of its two parts.’

A warm welcome: former Federal Minister of Education and Research Annette Schavan and former senator and CEO of the Charité Foundation, Jürgen Zöllner. Back row (from right): Detlev Ganten and the presidents of the three universities in Berlin: Jan-Hendrik Olbertz (HU), Jörg Steinbach (TU) and Peter-André Alt (FU).

Cornelia Yzer, > Senator for Economics, Technology and Research : ‘MDC has developed at a rate of knots. A new, high-impact paper ever y week. Three Leibniz award winners, one woman and two men. From the ver y beginning, cooperation between science and business played an important role at MDC. Now, with the common research area at BIH, a bridge is being built between clinical and research activities. This is a great opportunity for Berlin as a business location, too. MDC is as it is – not looking back on its birthday, but looking forward.’

< Professor Annette Schavan, former Federal Minister of Education and Research : ‘Happy birthday, and thank you ver y much for ever y thing you’ve done. One of the primar y aims of public and political responsibility in our countr y is to continue developing and internationalising universities and research institutes, creating more space for these hotbeds of innovation. We have to send out the signal that research, not just in Berlin but in the whole of Germany and Europe, is one of the sources of our future prosperity.’

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Professor Jürgen Mlynek, > President of the Helmholtz Association of German Research Centers : ‘We are proud of MDC. It’s a jewel in the crown of health research in the Helmholtz Association and beyond.’

< Dr. Manfred Erhardt, former Senator for Science and Research : ‘BIH is great. The Berlin Institute of Health will attract the best researchers from all over the world. There are already excellent scientists working at MDC. I still remember having sleepless nights because not all the staff at the old academy institutes were able to keep their jobs. It really got to me. Which is why I am all the more thrilled about this success stor y which has been jointly written by researchers from east and west.’

< Dr. Gudrun Erzgräber, former Managing Director of BBB Management GmbH : ‘I hope the development of MDC and, by extension, BIH, will continue to be just as magnificent and successful as it has been in the last two decades. In our time, Professor Ganten and I made a good team : he was the visionar y when it came to campus development ; I looked after the application side at the BioTechPark. There’s no other campus in Germany that can boast the same degree of cooperation between clinical and research activities and business. Biotech firms like that.’

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20 Years

of Science

20 years of the MDC A major exhibition showca ses the MDC’s scientif ic publications since it wa s founded 20 years ago T e x t l u cy pat t e r s o n P h oto s Dav i d Au s s e r h o f e r

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n 2012, the MDC celebrated its 20th birthday. Commemorating this, the MDC’s birthday bash on 7th December featured an exhibition – ‘20 years of science, 20 years of the MDC’ – on show in the Foyer of Haus 84 until the end of January. With a giant infographic, the exhibition depicts all 3,210 of the MDC’s scientific publications produced in the 20 years since it was founded. Each one is represented by a single ‘bubble’ along a 22 metre-long timeline from 1992 until 2012. The position on the y-axis represents the impact factor of the journal in which it was published, its size the number of citations, and its colour the MDC research programme to which the authors belonged. Immediately obvious is the sheer number of publications involved. And it doesn’t take much to realise what an incredible amount of work they represent. The fact that so many are high impact or highly cited is not only testament to the standard of the work, but also caused some problems in production of the exhibition: due to space constraints we* couldn’t add labels indicating title, journal, authors and lab for all the bubbles. To restrict

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the number of labels enough, we had to set the cut-off point at impact factor higher than 15 or more than 180 citations! In its way, this infographic tells the story of the MDC. There are relatively few publications in the early years as the new institute gradually finds its feet through the turbulent post-reunification period of the early 90s. But time passed and further investment helped the institute to grow and develop. Research data started to accumulate – it’s often said that a good paper can be 4 or 5 years in the making – until, around the end of the 90s, the MDC really hit its stride and the publication rate took off. In parallel, a lot has changed in science in the course of the last 20 years. To set the MDC’s publications in a wider context, the exhibition also includes some of the milestones from life science research: from big discoveries that changed the way we think about biology, to technological breakthroughs that have changed the way we work. Without the green fluorescent protein (GFP), we'd still be in the dark

For example, daily life in the lab was rather different 20 years ago. Imagine trying to do your research now

Absorbed in the exhibition: PhD student Matti Baumann.

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‘Wall of Fame’: The 22 metre Scientific exhibition received a lot of attention from junior scientists.

without the literature search engine Pubmed (publically launched in 1997). Even the internet itself was a novelty. There was no Powerpoint, microscope images were recorded with analogue cameras, and until the invention of automated sequencers in 1996 DNA sequencing was so painstaking (manually loading gels and then reading rows and columns of bands) that a single new gene sequence could qualify for a paper. Also, for example, it was only in 1992 that the sequence of GFP (a green fluorescent protein isolated from a jellyfish) was first published, and 1995 when improved variants turned it into a widely used tool. Used as a label in living cells, modern cell biology would be unimaginable without it. The first published use of GFP from the MDC was in 1997 by Cristina Cardoso and Heinrich Leonhardt (Cardoso et al., 1997). They had made a DNA ligase I:GFP fusion protein to study the timing and localisation of DNA replication for the first time in living cells. Back then this presented new challenges, e.g. keeping cells alive for long periods under a microscope. Similarly, it was only in 1994 that the first transgenic mice were made using the cre-loxP system, developed in part by Klaus Rajewsky, at that time in Cologne. Rather than knocking out a gene of interest entirely, it was now possible to disrupt genes at later stages of development or just in specific tissues. The first use of this technology at the MDC was by Alistair Garratt in Carmen Birchmeier’s group (Garratt et al., 2000). Among several groups at the MDC experimenting with the system in the mid to late 90s, Alistair recalls, ‘At that time we weren’t sure the

conditional knockouts would really work and our time investment would pay off. Recombination is never 100% and we were worried that the unrecombined cells might rescue the phenotype.’ Happily, this didn’t turn out to be a problem, and the system lived up to its promise, now a key tool for studying the role of genes in different contexts.

Concept of the exhibition by Luiza Bengtsson, Vera Glaßer, Lucy Patterson References: Cardoso et al. J Cell Biol. 1997 139:579-87. Garratt et al. J Cell Biol. 2000 148:1035-46. Behrens et al. Nature. 1996 382:638-42. Bladt et al. Nature 1995 376:768-71. Meyer & Birchmeier Nature. 1995 378:386-90

Ever y publication counts

The biggest bubble on the chart belongs to Walter Birchmeier for a paper (Behrens et al., 1996) describing for the first time the interaction between LEF1 and beta catenin in canonical Wnt signalling. Walter was among the first of the new group leaders to be recruited to the MDC in 1993 and offers this potential explanation for the success of his paper: In 1995, he was joined by his wife Carmen Birchmeier and her lab, who proceeded immediately to publish two big Nature papers (Bladt et al. 1995, Meyer & Birchmeier 1995). ‘The consensus of opinion around the MDC at that time was in danger of becoming, ‘Bright woman, shame about the husband’’, he explains, ‘so I felt I had to do something about it!’ However, size isn’t everything. Even impact factor is not always a good predictor of how important a piece of research will turn out to be. Every paper has its part to play. What’s clear is that the growing body of scientific work, represented in this exhibition, is the real legacy of our institute. No one could have predicted where these 20 years would take us, both here at the MDC and in life science in general. You have to wonder - what will the next 20 bring?

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20 Years of MDC Part 2 19 9 7-2 0 0 1 1997

1999 Life Science Learning Lab ‘Gläsernes Labor’

Three research labs not only offer in-service training opportunities for teachers and lab staff but, above all, experiment-based courses for school students in genetics, neurobiology, cell biology, ecology and chemistry. Open Day, 2000: head of lab, Dr. Ulrich Scheller, now Managing Director of BBB Management GmbH, demonstrating some experiments. Photo: Thomas Müller, © MDC

Nobel laureate at MDC

Co-discoverer of the structure of DNA, James Watson, on a short visit to MDC on 3 May 1997. He held the opening address at the Congress of Molecular Medicine. D. Ganten. James D. Watson at the Congress of Molecular Medicine. J Mol Med (Berl). 1997 Sep;75(9):615-7. Photo: Thomas Machowina, ©Springer-Verlag

1998 2000 Demonstration to save university hospital

Laying the foundation stone at FMP

Rain pelts down on the campus during the laying of the foundation stone for the new FMP (Research Institute for Molecular Pharmacology) building on 13 July 1998. Berlin Senator for Research, Peter Radunski (centre), and the then Director of FMP, Walter Rosenthal (right), lend a hand. Photo © BBB Management GmbH

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Jens Reich and many others demonstrating in front of Berlin’s ‘Red Town Hall’ against the closure of the university hospital in Berlin-Buch on 13 January 2000. The financial crisis surrounding the AOK health insurance scheme had sparked a cost-cutting debate on abolishing the university status of the two campus clinics run by Charité.

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Regal visit to MDC

On 29 September 2000, HRH Princess Chulabhorn Mahidol, President of the Chulabhorn Research Institut in Bangkok, Thailand, visited MDC. Professor Detlev Ganten (left) shows the princess around the Berlin-Buch campus. Photo: Uwe Eising, © MDC

2001 MDC.C

The new Communications Center (MDC.C) at the Max Delbrück Center for Molecular Medicine (MDC) in BerlinBuch. It was opened by Federal President Johannes Rau on 29 November 2001 on the occasion of the award ceremony for the German Future Prize.

Unveiled on campus

On 14 October 2000: a memorial to the victims of National Socialism who suffered euthanasia and abuse in the name of medical research. The memorial reminds us that scientists at the Kaiser Wilhelm Institute for Brain Research in Berlin-Buch used the brains of euthanasia victims for their research. The sculpture was created by Anna Franziska Schwarzbach and erected jointly by MDC, Max Planck Society (MPG, Munich) and German Research Foundation (DFG, Bonn). Photo © MDCPhoto /© BBB Management GmbH

Right from the beginning Dr. Iduna Fichtner, head of the Research Group E xperimental Pharmacology:

‘We work at the interface between experimental cancer research and clinical application. I am very happy to have had the opportunity to continue my research at the Max Delbrück Center after the reunification (of the two German states). I have gotten a lot of support here to found my company.’ Anita Glanz, receptionist at the front desk:

From left to right: Dr. Christoph Stölzl (Berlin Senator for Science, Research and Culture), Prof. Detlev Ganten (MDC Foundation Board), Dr. Gudrun Erzgräber (Managing Director, BBB Management GmbH), Wolfgang Branoner (Berlin Senator for Economics and Technology), unknown, and Till Behnke (Architects Heinle, Wischer and Partner) Photo: Uwe Eising, © MDC

Laying the foundation stone for the Communications Centre at the MDC

at the Max Delbrück Centre for Molecular Medicine (MDC) in Berlin-Buch on 13 July 2000.

‘I really enjoy dealing with people of various backgrounds here at MDC. In my ‘glass box’ I am visible to all. Hence, the majority of the staff knows me. I do not even need to look up when many of them pass by. I recognize them by the sound of their footsteps. I know the campus since my early childhood. A lot has changed throughout the years. Today, I sit at the front desk and am part of the success story.’ Frank-Peter Kirsch, V ice Manager

‘20 years MDC - that means for me: state-of-the-art and exciting research – which always was and still is directed towards past, present and future (perspectives). It's a pleasure to be part of this process, to say thank you and to bring new ideas.’

of the Safet y Group :

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LinkedIn is good,

face-to-face is bet ter MDC research alumni talk about their science and careers

Alumni discuss diverse careers: Junior scientists listen intently.

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he MDC’s 20th birthday celebration brought together not only current staff and an impressive cohort of prominenti from science and politics, but also an enthusiastic group of former MDC researchers. The first MDC research alumni meeting took place on the eve of the big day in December and attracted about 60 former PhD students, postdocs and group leaders. They came from as far away as Brazil, the USA, China, Canada, India, and other corners of the globe, responding to the call of their alma mater. The meeting’s scientific symposium

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featured research updates from six alumni who currently head their own labs or institutes. The keynote lecture was delivered on the theme of ‘Immune regulation and cancer, on this and the other side of the Atlantic’ by Klaus Rajewsky, who ought to know: He recently moved his group to MDC after nearly half a century of remarkable research carried out in Germany and the USA. In addition to lively scientific and personal exchanges, another six alumni reflected on their diverse careers in academia and industry at a panel discussion of the MDC Career

Pathways Special. The festive lights glittering on early December snow made a suitable backdrop for the festive St. Nikolaus’ Day dinner. In a cosy restaurant on the banks of the river Spree they revived old friendships, met other alumni, and ‘LinkedIn’ the old-fashioned way – over a cold beer and a well-roasted duck. Oksana Seumenicht

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Passionate physician and scientist: Ahmed Abdelaziz knows that he is needed in Egypt.

cairo,

t h e cit y t hat n e v er s leeps Despite the hard working and living conditions, MDC alumnus A hmed A bdelaziz decided to go back to his home countr y, Egypt. Because he knows he can make changes there.

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uring the alumni dinner, Dr. Abdelaziz frequently looks at his smartphone. ‘One of my students is updating me on the situation,’ explains the professor from the German University of Cairo (GUC). Thousands of people are protesting in Cairo against the authoritarian measures imposed by President Morsi. Meanwhile, Ahmed Abdelaziz discusses with other alumni why he decided to go back to his home country. The unrest has seeped into lab life. Abdelaziz now holds some lab meetings by the Nile, where he and his students discuss work and the political situation. His passion for his country and his wish to make changes have driven him to where he is now. Trained as a medical doctor in Cairo, he decided to do a PhD in Europe. ‘I believe that a good doctor needs to know about clinics and research equally,’ he says. He found a mentor in Prof. Morano at MDC and received his doctoral degree from Charité and Humboldt-Universität. He continued his research career as a postdoc at the University of Calgary in Canada, but soon got an offer to return to Cairo. ‘The experience in Canada was great, but it was too cold and

not comparable to Germany. I always knew that Egypt was my final destination,’ he explains. He proceeds to talk about Cairo, a city that never sleeps, where the sun always shines and people are warm and approachable. Starting his work as a principal investigator at GUC, Dr. Abdelaziz wanted to tackle medical problems relevant to the Egyptian population. He had observed a high incidence of hepatitis C, hepatocellular carcinoma, and lupus erithromatosus in his private practice. After talking to Dr. Leonid Karawajew during a scientific visit to Berlin, he decided to investigate the role of microRNAs in these diseases. His lab has now published many peerreviewed articles on this topic and is focusing on personalised medicine for Egyptian patients. But doing research at an Egyptian university is not easy. ‘In the time that it takes me to prepare a paper in Egypt, I could have published three in Germany,’ he explains. ‘Sometimes we order reagents and they get stuck in customs for weeks. Once we receive them, they are unusable.’ Yet it does not sound like any of this discourages him. ‘I always preferred to start things

from scratch,’ he explains. ‘I knew that my added value to a research institution would be higher if I went back to Egypt.’ Another look at the smartphone. He expresses his hope that the revolution will improve the situation in his country. ‘My students were at Tahrir Square, and I am amazed by how persevering they are. I teach my students science and they teach me life.’ Nuria Cerdá-Esteban

Everyday life at the university during the Arab spring: Ahmed Abdelaziz with his seminar students.

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Lehrer for tbildungsprogramm Labor trifft Lehrer a m M a x- D e l b r ü c k- C e n t r u m f ü r m o l e k u l a r e Medizin ( MDC) in Berlin-Buch

A Finger on the

Pulse of Science T e x t Ma i m o n a Id

‘I could keep doing this a lot longer’: Thomas Rzesnik exchanges his teacher’s desk for the lab bench.

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P h oto s M i c h e l e C a l i a r i

homas Rzesnik knows all about fine-motor work. In his time, he has dissected the delicate trigger hairs of the Venus fly-trap and severed bees’ antennae in order to insert dye through their tiny channels to turn the insect’s brain red. But that was more than a quarter of a century ago. Now he's back in the lab for the first time since. ‘It all feels so familiar. I'm walking on clouds,’ raves the 52-year-old. His regular place of work is the classroom. Today, he has traded the teacher’s desk for a seat at the cryomicrotome. He sits there completely engrossed in his work at the modern precision instrument, worth several thousand euros, that produces microscopic tissue samples from deep-frozen material. With a fine brush, he picks up one of the flimsy samples from the cooled microscope stage. A critical moment, because the tissue that measures only a few micrometres

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Making tissue sections demands lots of dexterity from Annett Reich.

will collapse and fold if it is not fixed on the slide fast enough. The delicate structures of the tissue sample must not get damaged so that the dyed cells can still be examined under the microscope later. It requires a steady hand and a certain amount of routine. After a few attempts, the biology teacher gets the hang of it and is thoroughly enjoying himself. ‘I really feel I’ve accomplished something. I could have gone on doing this for hours.’ Thomas Rzesnik, who teaches at the Röntgen Schule in Berlin, is clearly a happy man. Direct contact with current research

The MDC teacher training programme ‘LTL’ offers educators from different types of school the opportunity to experience current research at a top institution hands-on. Today’s class deals with the function, structure and pathology of the nervous system and is taking place in Professor Carmen Birchmeier-Kohler's working group, “Developmental Biology and Signal Transduction in Nerves and Muscle Cells”. Scientists Dr. Hagen Wende, Dr. Thomas Müller and Dr. Michael Strehle explain the various methods they use in their work in Molecular Biology.

Together with biological technical assistant (BTA) Maria Braunschweig they mentor the participants. The teachers are particularly impressed by their visit to the Department of Electron Microscopy, where head of department Dr. Bettina Purfürst shows them the innovative high-resolution equipment. The one-day workshop for teachers is clearly focused on practical work. After a theoretical introduction, the six educators have to roll their sleeves up. They are not expected to pipette colour solutions for their own sake, but rather to learn relevant methods that are standard in any research lab. ‘This way, we give our participants a realistic insight into the latest scientific findings and the daily routines of lab workers and scientists,’ Dr. Luiza Bengtsson explains. The biochemist launched the programme at MDC about eighteen months ago. The strategy is based on small groups and hot research topics that can be addressed in teaching at school level. To ensure the training session has a sustainable impact on their teaching, participants leave with didacticised teaching and ancillary materials as

well as the products and samples they have made during the workshop. They can incorporate these into their lessons and pass on what they have learned to their pupils. Dr. Annett Reich and her other colleagues graduated from university decades ago. The chemist wants to keep pace with the latest scientific developments for her pupils’ sake. ‘Many of my pupils want to go to university. I’m doing my best to make sure they are ready to meet the demands of university life,’ says Reich, who teaches at the CharlotteWolff-Kolleg in Charlottenburg-Wilmersdorf. She will only succeed if she can make her subject fun and spark her pupils’ enthusiasm for it. With cutting-edge research topics and the materials from the workshop she hopes to be able to impress them. The mood in the Max Delbrück research lab is exuberant. Clad in MDC lab coats, Annett Reich, Stefanie Rieck and Grit Herrmann look over the shoulder of lab assistant Maria Braunschweig as she pulls a particularly delicate tissue sample out of a saline solution. The three of them will have to do the same in a minute. They are amazed how much craftsmanship and skill this work takes. Tasting the

Delicate tissue: Grit Herrmann exercises care in positioning the specimen on the slide.

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works for the communications department. She is particularly keen to highlight the significance and importance of basic medical and scientific research, and wants to foster understanding and acceptance of it. Moreover, young people should be able to form their own opinions about headlines or newsflashes such as “Broccoli will protect you from cancer”. But they can only do so if they have a solid grounding in science, which is supposed to be taught at school. Luiza Bengtsson: ‘It is through the teachers that we reach the pupils, and today’s pupils are tomorrow’s society.’

Learning instead of teaching: The teachers learn everything that matters from BTA Maria Braunschweig (middle).

‘It’s nice to get people excited about our work. It really boosts your confidence, because research can get ver y frustrating at times’

exciting world of the lab seems to be going to the teachers’ heads. Much to Maria Braunschweig's delight, they are all in high spirits. It makes her think of her own school days. ‘The teachers remind me a bit of pupils. They chat and lark around,’ laughs the 27-yearold MDC assistant. They have not mastered all the techniques yet, but the teachers have made a pretty good job of it, she thinks. Thomas Müller, Hagen Wende and Michael Strehle are thrilled by the positive feedback and genuine interest in their work. ‘It’s nice to get people excited about our work. It really boosts your confidence, because research can get very frustrating at times,’ Müller says. Michael Strehle has enjoyed being asked so many questions about his presentation. ‘What the participants get to see here goes well beyond the experiments they do at school. It’s a real

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highlight for them.’ Ultimately, he and his two colleagues also benefit from ‘LTL’. They learn to communicate their complex and difficult work to others. The scientists know how essential this is and feel that communication is part of their work. ‘The research we’re doing here is very expensive and paid for by the tax payer. The public quite simply has a right to know what is happening here,’ Wende stresses. ‘People should see that what we are doing here isn't voodoo, ‘Thomas Müller adds. Programme director Luiza Bengtsson can only agree. ‘The notion that science spawns ground-breaking new insights every day of the week is not quite accurate. The workshop gives teachers an idea how work-intensive research really is and that usually, success is the result of many tiny building blocks coming together over long years of teamwork’, says Bengtsson, who

High-tech in the lab: René Eichhardt slices cell tissue at the cryomicrotome.

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Open Ear

An ‘honorary member’ joins the newly elected Staff Association: Hermann von Helmholtz (in the blue jacket): Dennis Siuchninski, Dr. Dennis Kobelt, Rainer Leben, Elke Güttler, Dagmar Gerhard, Ingo Kahl, Signe Knespel, Dr. Jana Dröse, Lutz Else and Dr. Alexander Löwer (from left to right).

Championing the interests of MDC colleagues : the newly elected Staf f Council

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ith a turnout of 43 percent, MDC staff elected their new Staff Council on 3 and 4 December 2012. Election committee members Martin Flachmeier, Petra Haink, Bettina Krause and Jana Richter made sure everything went smoothly. Since the number of staff at MDC has passed the one-thousand mark, the number of council members has increased to thirteen. During this four-year term, newly elected members Manuela Adloff, Dr. Jana Dröse, Lutz Else, Robby Fechner, Dagmar Gerhard, Elke Güttler, Ingo Kahl, Signe Knespel, Dr. Dennis Kobelt, Rainer Leben, Dr. Alexander Löwer, Dennis Siuchninski and Corinna Volkwein will assume the tasks of representing the staff.

At its first session, the Staff Council elected Jana Dröse, Lutz Else, Dagmar Gerhard and Ingo Kahl to the board, with Ingo Kahl being re-affirmed as chairman. For the last four years, he has been involved in the activities of the Staff Council and since 2009, has been on leave from his original duties to represent staff interests full-time. ‘We are there for all the colleagues at MDC and will listen to any concerns or questions,’ he stresses. Jana Dröse is new to the Staff Council. ‘MDC lives and grows through its staff members. That’s why I think it’s important to stand up for their interests,’ says Dröse, who is an officer in the PhD office. IT specialist Dennis Siuchninski is also new to the Staff

Council. Being a link between employer and employees is a great challenge for him. ‘I don’t just want to complain when things go wrong, but get things moving in the places that count,’ he emphasises. The core tasks of the Council are issues relating to employer-employee relationships and the workplace, such as the terms and conditions of employment, temporary contracts and employment agreements. But they also deal with other topics like opportunities for individual development and combining work and family. The Staff Council sees itself as an important element of internal democracy and Ingo Kahl is pleased that his re-election will allow him to continue and expand his work on the Staff Council. Further themes that are important to him are conflict-mediation and psychological stress at work. ‘This is why I trained to become a fairness and conflict advisor,’ he says. The Staff Council has also made it its declared goal to campaign for longer-term and indefinite-period contracts at MDC in order to offer staff secure prospects for the future. ‘Research is a tough field to work in, and it has its own rules. As the Staff Council we want to campaign for fair play, ensure that every staff member is given opportunities and that nobody falls by the wayside,’ says Ingo Kahl. One of the Staff Council’s crucial tasks will be to represent employees’ interests during the building and development of BIH (Berlin Institute of Health). Id

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Strong Partners From China Great interest in German research : the Chinese Amba ssador's f irst New Year’s engagement brings him to the MDC T e x t Ma i m o n a Id

P h oto s Dav i d Au SSe r h o f e r

‘Traditional Chinese medicine and modern Systems Biology go ver y well together.’

Chinese Ambassador Shi Mingde in Dialog with MDC Director Walter Rosenthal.

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uch was the surprising conclusion of Chinese Ambassador Shi Mingde on his visit to the Max Delbrück Center for Molecular Medicine (MDC) on 3 January 2013. He has been the senior representative of the People's Republic to Germany since August 2012. His compatriot, Dr. Wei Chen, working group leader at MDC's Berlin Institute for Medical Systems Biology (BIMSB), had just introduced the diplomat and his delegation to Systems Biology, which considers the organism and the processes in its cell metabolism in their entirety. A holistic approach of this kind is also the hallmark of Far Eastern Medicine, the Ambassador noted at his first engagement of the New Year. MDC's Scientific Director, Professor Dr. Walter Rosenthal, presented the Center and the Buch

Campus to the Chinese guests in an informal atmosphere, stressing the high degree of internationalism. A third of all MDC employees come from more than 70 countries; 47 Chinese scientists work here, 15 of them as visiting researchers. Independent innovation

When it comes to science and research, China is striving for independent innovation – that means original inventions rather than imitations. The party leadership's ambition is to make the People's Republic a leading research nation. “In the last years, China has taken great strides in research, which makes it an ideal partner for us," Walter Rosenthal stressed. The MDC Scientific Director attaches great

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‘Sino-German collaborations hold great promise for the future,’ writes Chinese Ambassador Shi Mingde in the MDC guest book.

The Chinese Ambassador (right) likes the holistic approach of Systems Biology, here with BIMSB group leader Wei Chen.

importance to basic research, an area in which Ambassador Shi Mingde also saw common challenges. ‘Basic research seldom produces results that can be applied quickly, which is why it isn’t easy to convince the public of its usefulness. We are facing the same issue,’ the diplomat said. After a brief introduction, MDC scientists Professor Dr. Michael Bader (Molecular Biology of Peptide Hormones), Associate Professor Dr. Enno Klussmann (Anchored Signalling) and Dr. Wei Chen (Systems Biology of Gene Regulatory Elements) provided an overview of their current research results. Afterwards, the delegation visited the BISMB laboratories. The representative of the People's Republic was particularly eager to meet Chinese PhD students working at MDC. He

passed on New Year's greetings to the doctoral candidates in Chinese and appealed to them to embrace German culture so that Germans and Chinese could get to know one another better. ‘The young are the future of our country. Use this opportunity to learn, whether you stay in Germany or return home to China’, the 58-year-old encouraged his compatriots. PhD student Hua Jing said she was going to heed one of the Ambassador's recommendations, in particular. The 2012 Curt Meyer Memorial Prize winner will complete her graduate studies with Clemens Schmitt's working group at MDC this year. Shi Mingde told her and her colleagues: ‘Health is our most precious gift. Stay healthy, and above all, happy. Try to avoid stress at work and focus on a fulfilled life.‘

Ambassador Shi Mingde (2nd from left) is delighted to meet a few Chinese nationals at the MDC.

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Running the Runway The MDC runners came in 93rd in a field of 1,079 at the 20th Berlin Marathon Relay on the site of the former airpor t at Tempelhof

‘Only in Berlin.... Where else could you run laps past aeroplanes on a runway?’,

asks an enthusiastic Dr. Ulrich Gohlke. This is the scientist's fourth year with an MDC running group, where he trains regularly with colleagues. At the 20th Berlin Marathon Relay at the former airport, Tempelhof, the MDC Bond Angels were the second fastest group from the Max Delbrück Center, finishing in three hours, eleven minutes and 41 seconds. They only had to cede to the MDC Artists, an all-male team whose seven-second lead over the Bond Angels earned them 93rd place amongst 1,079 competing groups Running instead of flying

She sets a good example: Dana Lafuente, Coordinator of the Administrative Directorate Photo: Maimona Id

On a foggy November Sunday, about 7,000 runners gathered to compete at a place that once used to be bustling with air traffic. A new option this year was the half marathon distance of 21.0975 kilometres. Since 2008, MDC’s Society of Friends has covered the registration fees for the eight MDC relay teams with more than 30 runners. Among them is runner and organiser Dana Lafuente. ‘MDC is one of the most successful health and prevention research centres worldwide. It’s only right that we motivate our staff to take regular exercise,’ emphasises Lafuente, who is an administrative coordinator in the Administrative

Fun and team spirit are the focus for MDC jogging groups. Photo: Dana Lafuente

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Directorate. Every year, Ulrich Gohlke, the Bond Angels’ team captain, tries to recruit enough runners for the relay. Everyone is welcome. ‘Some people are not very sporty and don't start training until two months before the race. But it’s not about setting records, it's about having fun with colleagues,’ the researcher notes. What counts are team spirit and the shared experience. ‘You get to know each other on a completely different level than in the office or the lab,’ Gohlke comments. For Dana Lafuente it is important to promote a feeling of shared identity amongst the more than 1,600 employees, that is not work-related. ‘With an average age of 38, we’re a very young centre. Everyone has a heavy workload. Sports are fun and give us an opportunity to meet and talk about other things apart from what goes on in our labs and offices,’ she says. She is delighted to have discovered so many talented runners at MDC and hopes to see many new faces at the different races that MDC’s Society of Friends will sponsor in 2013, among others the 'Berliner Firmenlauf' on 24 May and the 'allod Gesundheitslauf' on 14 September. Id You will find all MDC records under : www.mdc-berlin.info/de/ infrastruktur/Sports/index.html

Information about ‘Freundeskreis’ under: www.mdc-berlin.de/Freundeskreis

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Politics

m ee ts Scien ce

The MDC’s first parliamentar y evening a success

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ECRC scientist Dominik Müller explains to some of the guests why animal experiments are crucial.

the same time, he and Professor Dr. Nikolaus Rajewsky underlined the importance of close cooperation with Berlin universities. MDC researcher Rajewsky, who coordinates BIMSB, presented the work being conducted by researchers in systems biology and later spoke about the plans to construct a major new building on the north campus of Humboldt-Universität (HU) in Berlin-Mitte. HU President Professor Dr. Jan-Hendrik Olbertz stressed the central role of collaboration between MDC and HU, particularly in the new Integrative Research Institute for the Life Sciences (IRI) on HU’s north campus.

hree major themes were the focus of attention at the first parliamentary evening held by the Max Delbrück Centre for Molecular Medicine (MDC) last October: animal experiments, the upcoming collaboration between Charité and MDC at the Berlin Institute of Health (BIH – also the subject of the cover story) and the Berlin Institute for Medical Systems Biology (BIMSB). MDC stakeholders presented the themes in short discussion rounds at the Humboldt Carré am Gendarmenmarkt which were followed by snacks and more discussions with parliamentarians and guests from Berlin universities and non-university research institutions.

Inform about animal testing: Thorsten Karge (SPD), Brigitte Jenner (Publications officer of Tierversuchsgegner Berlin und Brandenburg e.V.) and Simon Kowalewski (Piratenpartei).

Cooperation of Charité and MDC

Importance of animal testing

Professor Dr. Walter Rosenthal of the MDC Board of Directors, for example, explained how important cooperation with Charité – Universitätsmedizin Berlin is to MDC. ’The results of our basic research can only find their way into applications in combination with excellent clinical partners – and that’s what we have at Charité.‘ Translational medicine was not a one-way street, Rosenthal emphasised. The dialogue between doctors and clinical researchers and scientists conducting fundamental research would become even more intensive. ’A shared roof over our heads will give us the appropriate space to do so‘, said Rosenthal. At

Finally, Dr. Boris Jerchow, head of the Transgenic Core Facility at MDC and deputy head of the Animal Facilities, and Dominik Müller, research group leader at MDC and professor at Charité, explained the necessity for animal experiments in fundamental biomedical research. MDC’s plans for new animal facilities with modern, integrated laboratories (In vivo pathophysiology laboratory, IPL) had met with opposition from animal rights organisations and some parliamentarians. Protesters picketed outside the Humboldt Carré for some of the time, but the debates inside at the parliamentary evening concentrated on the facts of the matter. vg

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C u lt u r e s ’ c al e n da r s Passover 26th March to 2nd April 2013

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Passover One of the most famous Jewish festivals tells the stor y of the exodus of the Israelites from Egypt. Inbal Ipenberg remembers what it means for her. Te x t Inbal Ipenberg

P H oto L u cy Pat t e r s o n

Passover holiday, which is celebrated for seven days starting every year on the 14th day of the month of Nisan (according to the Hebrew calendar). I remember well celebrating the festive dinner called Seder that marks the beginning of the holiday, particularly the special kosher food that conservative Jews serve during Passover. Unfortunately, I suppose, the principles and dogmas I have adopted over the years have turned me into a vegetarian – which makes it a challenge to plan a kosher diet during the holiday! You can find something, but it won't necessarily be both vegetarian and tasty. Leavened breads are taboo ‘On Passover mornings, the special holiday foods drew us out of bed’: PhD Student Inbal Ippenberg has lovely childhood memories of Passover.

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he Passover holiday, or ‘Pessach’ in Hebrew, is a holiday that commemorates a story found in the book of Exodus in the Hebrew and Christian Bibles. The legend recounts how the people of Israel escaped to Egypt during a period of drought and horrible famine. They settled down and lived in peace for many years until a new Pharaoh acceded to the throne. Fearing the increasing power and numbers of

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ethnic Israelis in his country, he enslaved them and subjected them to various other cruelties. After hundreds of years of labour devoted mainly to the glory of the Pharaohs, the legend goes, Moses led them to freedom. The Egyptian king did not get off lightly; after ten godsent plagues, the Pharaoh decided to let the people of Israel return to their homeland. This is the traditional origin of the seven-day

Several criteria must be fulfilled to celebrate the holiday in a ‘kosher’ way. The main ritual involves getting rid of all the leavened food (anything made from wheat, barley, and so on). This stems from another part of the Exodus legend: the Israelis were in such a rush to leave Egypt (rightly fearing that the Pharaoh would change his mind) that the dough in the pastries didn’t have enough time to rise and all of the breadstuffs remained flattened. So conservatives refrain from leavened

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foods and various grains during the Passover holiday; they use only specialised ‘matza flour’, which lends its name to the flattened special bread of Passover. So now, in the days leading up to Passover, traditional Jewish households get rid of all sorts of leavened food and clean up to eliminate any traces of unkosher food. My father used to hide slices of bread and pita-breads in small bags around the house, which we had to find by candlelight before the house was ready for the holiday. Some families burn their leavened food before the holiday; others sell it to non-Jews. The latter is considered a symbolic ritual and is usually performed by a key community figure such as the chief rabbi of Israel.

specific order. The Seder organiser, usually the eldest person in the family or the father, blesses the food and drinks and instructs the family on the dinner rituals. It is considered a commandment for everyone at the dinner to participate in reading the Haggada. These customs make everyone feel as if they had just been freed from slavery in Egypt and had taken part in the fatiguing journey back to the Holy Land. During the Seder dinner we eat different dishes that symbolise many aspects of the Exodus legend. For example, we eat a bitter herb (horseradish or lettuce heart) that symbolises the hard times that the people

The Haggada is full of the stories of the legend and songs, but I think that most of the families celebrating the holiday are eager to get to the part with the dinner itself, and skip most of it. The Passover holiday lasts for seven days, in which conservative people eat only kosher food. At the end of the holiday, Jewish people who are originally from the north of Africa (Morocco, Libya and so on) celebrate another holiday that is called ‘Mimouna’. The main goal of the holiday is to celebrate and have a good time while eating vast quantities of colourful sweets that are mostly made of kosher ingredients. The non-kosher, famous Mimouna-pancakes called ‘mufletas’ are prepared just after the Passover holiday has finished.

My favorite : Matzen with chocolate cream

In addition to a general house cleaning, the kitchen needs to be specially prepared for the holiday. My family has a set of dishes that only comes out at Passover and will always symbolise the spirit of the holiday and the festive environment to me. Some families use everyday dishes and make them kosher by immersion in boiling water. My parents tucked away all the non-kosher dishes in the closets, with a special kosher closet reserved for holiday dishes and food. I really liked Passover morning, when we woke up to a festive diet. My favourite dish was, of course, matza bread spread with chocolate. Bitter herbs symbolize slaver y in Egypt

The first evening of Passover brings the festive dinner called the ‘Seder’. The family gathers around the dinner table and reads from the ‘Haggada’, which recounts the Exodus legend. It is also customary to invite people who have no-one to celebrate with, or don’t have the means to celebrate the holiday. The Haggada spells out all the rituals of this festive dinner, which should be carried out in a

of Israel suffered in Egypt, and their slavery. In addition we eat Charoset, which is a sweet paste made of dried fruit and nuts as a symbol for the mortar the people of Israel used for building the pyramids and other structures, as part of their slavery (according to the legend, at least). One of the nicest rituals of the Seder is the hiding of a piece of matza that is called “Afikoman”. The Seder organiser is supposed to hide a piece of matza during the Seder dinner, in such a way that the other diners will not notice, and the kids that participate in the Seder compete with each other in trying to find this Afikoman. The one that finds the Afikoman gets a gift. Except for one time, I never found the Afikoman piece, and as far as I remember, neither did my young brother. My grandfather used to hide it so well that we all suspected that he didn’t really hide it anywhere!

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We’ll share a cup M D C ’s m u l l e d w i n e s t a l l m a ke s 1,370 euro for young people on the streets

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Foto: David Ausserhofer

ho needs an entire Christmas market? MDC had its own mulled wine stall. With bracing temperatures, a fresh layer of snow and a cheery fire, the little wooden hut in front of the Hermann-von-Helmholtz-Haus this Christmas was a welcome after-work destination for the staff of the Max Delbrück Centre. Hot drink in hand, colleagues found a pleasant way to end the working day or pass the time waiting for the bus and do a good deed at the same time: the organisers around Lucy Patterson from the Communications Department made 1,370 euro which went to Klik, a drop-in centre for young people living on the streets. The project is completely financed by donations and endowments. It provides young, homeless people in Berlin with the chance to have a shower, wash clothes, eat a hot meal and get advice. “Activities like this are good for encouraging a team spirit on campus and also help a good cause,” Lucy Patterson emphasises. She was delighted that so many colleagues from the research groups and administration showed their support by helping out at the mulled wine stall. Id

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In a nutshell Money for new microscopes: MDC Director Walter Rosenthal presents to reverend Hagen Kühne the privately collected donation for the protestant primary school.

New Year’s reception for the Berlin-Buch campus communit y

The link between excellent research and knowledge-based business was the core theme at the New Year’s reception for the campus community on 25 January which brought together MDC, Charité, FMP (Leibniz-Institut für Molekulare Pharmakologie) and berlinbiotechpark. As guest speakers, this year’s hosts, BBB Management GmbH, invited Dr. Andreas Eckert, Chairman of the Board of Eckert & Ziegler AG, and media and science entrepreneur, Sebastian Turner. A welcome address was given by Guido Beermann, State Secretary in the Berlin Senate Department for Business, Technology and Research. MDC director, Walter Rosenthal, was delighted to present a donation of 1,000 euro to Reverend Hagen Kühne, Chairman of the Board of the newly-founded Protestant primary school in Berlin-Buch. The money partly came from private donations by staff at MDC and partly from a collection taken during the festivities to celebrate 20 years of MDC in December

Elections for Youth and Trainee Council (JAV ) 2013

Career Day 2013

Christopher Suckel (trainee IT specialist), Lisa Hügel (trainee animal carer), Lisa Mallis (biology lab assistant), Martina Kneiseler (trainee animal carer) and Vivien Rabke (trainee animal carer) were elected onto the Youth and Trainee Council on 23 January 2013. JAV works together closely with the Staff Council and attends to the concerns of trainees.

Everything you always wanted to know about career paths in science. This is the focus of MDC’s Career Day on 11 April 2013. Lectures, panel discussions and company presentations will tell you about the opportunities for careers outside academia. Visit: www.mdc-berlin.de/careerday

Mongolian Education Minister at Max Delbrück Center During a visit to MDC on 25 January, Mongolia’s Education Minister, Luvsannyam Gantumur, took the opportunity to learn more about MDC’s research and doctoral training from Professor Dr. Walter Rosenthal, Chairman of the Board and Scientific Director of MDC. The Central Asian country with a population of 2.7 million is building a German-Mongolian University in its capital, Ulan Bator, and is interested in collaborating with German research institutions and exchanging doctoral students.

Mongolian Education Minister Luvsannyam Gantumur (lef t) with MDC director Walter Rosenthal, and members of the delegation in the second row. Photo: David Ausserhofer

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Reaudit Job and Family at MDC : successf ul reaudit

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aving successfully implemented the measures recommended in the 2009 ‘audit berufundfamilie’ (an external assessment to promote sustainable family-friendly policies at work), MDC decided to conduct a reaudit in 2012. It now offers many options to help combine job and family, ranging from the Welcome Centre, campus daycare centre and young scientists summer schools through flexible working times to reintegration and dual career opportunities. The Board

of Directors pursues personnel policies that are essential if MDC is to recruit the best staff and talents and focus on scientific performance; the Board expects everyone in a leadership position at MDC to perceive their leadership responsibilities accordingly. In the next three years, the successful programmes will be continued and complemented by new options, such as low-cost holiday accommodation and travel for children and young people offered by the ‘Sozialwerk Bund’.

Contac t Dana Lafuente Coordinator

of the Administrative Directorate MDC / house 84 / room 1110 Tel. 0049(0)30. 9406-2490 [email protected] Gabriele Kollinger

Human resources development MDC / house 84 / room 1209 Tel. 0049(0)30. 9406-3715 [email protected]

MDC Summer

Researchcamp2013

June 24th – 28th 2013

For more Information contact Dr. Bärbel Görhardt BBB Management GmbH Gläsernes Labor| Forschergar ten Mail b.goerhardt @ bbb-berlin.de Fon +49(0)30. 9489 2923 Fa x +49(0)30. 9489 2927 application deadline 30th April 2013

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Photos: Shutterstock, David Ausserhofer

on the Berlin-Buch Campus for boys and girls ages 11-14 Bring your sleeping bag and a light mat tress to spend the night in the Life Science Learning Lab ‘Gläsernes Labor’ | meals and drinks provided. 24-hour professional super vision. | Fee covers transpor tation and all course materials co-payment 180,00 Euro p.P.

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W hether in the MDC Research Camp or lab courses in the Life Science Learning L ab ‘Glä sernen L abor’,

the holiday research progr am is exciting

adventure

Time

09.00

10.00

11.00

12.00

13.00

14.00

knowledge 24.06.

Geocaching: An electronic treasure hunt for the 21stcentury – Getting to know each other

25.06.

Learning in your sleep: A visit to a sleep lab brings the secrets of the night brain to light

A mysterious new model organism: Naked mole rats don't feel pain – on the trail of a fascinating mammal

17.00

18.00

Who is the killer? Carry out advanced criminal detection techniques such as DNA analysis and obtain your ‘laboratory driver's license’

Power from wind, the sun, etc.: Take a look at regenerative energy on campus during the Green Campus Day, Windkraft, Solarenergie und Co:

Dancing with Wolves – spend a day studying animals during the WildLife Day at the Wildpark

28.06.

The Aztecs had good taste: Learn what's in a cocoa bean and how chocolate is made

GPS-Rallye: Discover the Buch campus using satellite signals Picnic (covered in the course fees)

Bowl like an expert in B1 Schöneiche.

19.00

Grill party 20.00

27.06.

Muscles count! A different view of rail travel on the bogie

15.00

16.00

26.06.

Progr am

Campfire: Make your own Geocache on campus

Film evening with popcorn

Courses in the lab

Guided tours and excursions

Social programme

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A feeling for students: Ombudspeople Daniela Panáková and Thomas Sommer look out for the interests of junior scientists.

The ‘PhD’s Pastoral Caregivers’

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PhD students, Nadine Richter and Cornelia Hainer, spoke to both researchers about their work as the ‘PhD's pastoral caregivers’.

Photos: Michele Caliari

In October 2012, PhD students at MDC elected a new ombudswoman: Dr. Daniela Panáková. She has headed her own working group at MDC since summer 2011 and will now share the office of the ombudsperson with Professor Thomas Sommer. He has been at MDC since 1993 and has had a few years to gather experience in the field. PhD students, Nadine Richter and Cornelia Hainer, spoke to both researchers about their work as the ‘PhDs’ pastoral caregivers’.

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What sort of problems do doctoral students experience? Thomas Sommer: Usually students come to me with issues that result from a breakdown in communications – things like third-party funding agreements, deadlines for reports or authorship of publications. Communication about authorship can breakdown when a former doctoral candidate is already working somewhere else as a postdoc and is no longer in direct contact with the group leader. When working groups break up and doctoral students have to move away, even though the end of their doctorates is in sight, it often makes their private lives very difficult. They may have to find a new working group in order to complete the project. And often it’s all about the bureaucracy that’s involved when students come from universities abroad that have different rules and regulations. Daniela Panáková: When I took my doctorate at The Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, the group was comparatively small and I got a lot of support from the group leader. So I didn’t need to approach the ombudsperson at the institute. But if I’m absolutely honest, about 80 percent of what you experience in science is quite frustrating, so problems are inevitable. There is no recipe for success. And, in many cases, students and group leaders don’t communicate when the project isn’t going as well as expected. It’s really important to recognise this quickly and keep discussing the difficulties. Of course, I’m hoping there won’t be so many problems, and all the students are happy.

dent’s problems and make suggestions, but I can’t take on the supervision. However, I can draw the group leader’s attention to any problems the students might be having. These could be very different and have a lot to do with the individual student. Some work very independently; others need more guidance and regular, targeted mentoring. The group leader can’t guess what students need – they themselves have to make clear exactly what they want and, if necessary, put some pressure on to get it. As an ombudswoman I can try to mediate, speak to the supervisors and find solutions for the problems they’re having – because good relations between students and their supervisors and constant communication are the be all and end all of a successful project. Thomas Sommer: The sort of help I can give depends on the problem. First of all, I speak to the students about their concerns, and that is often enough to get things sorted. If the situation is more complicated then I would contact the group leader – with the student’s permission. However, students often worry that this will have negative consequences for them.

If the parties really get entrenched, I try to get them talking again because a good atmosphere in the working group is what matters. The three of us would then get together, or involve another person, another group leader, for example. The object is to make sure everyone can make their own point of view perfectly clear so that we can find a pragmatic solution for the doctoral student. So far, I think this strategy has been pretty successful.

What could be done at the institute to improve the situation for PhD students? Thomas Sommer: The mentoring situation is much better now than it was when I first started. Since then, annual PhD Committee Meetings have been introduced which give doctoral candidates an opportunity to discuss their projects with two other group leaders and possibly get some new ideas and advice. This helps them get out of a rut. For many students, especially at the beginning of their doctorates, it would be helpful to show other group leaders a rough draft of

What kind of help can the ombudsperson provide? Daniela Panáková: As an ombudswoman, I can listen to the stu-

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Photos: David Ausserhofer

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their projects so that they’re not stumbling around in the dark in the initial phase. They need a sort of road map which they can go on to develop themselves. The supervisor’s job would then be to order the woolly thoughts of ‘fully-fledged students’. What makes you want to be an ombudsperson? Thomas Sommer: It’s always nice to help others, of course. You see how students are developing, changing and growing with their success. As time goes by, they become more confident and realise that the others are all in the same boat, too. But I have to say that, given the large number of doctoral candidates at MDC, I’m very seldom consulted, which I hope doesn’t mean they don’t trust me! Lots of things are now done by the Graduate Office. I’ve hardly had any unpleasant experiences. I don’t very often get any feedback, but I assume all is well if I don’t hear anything. I really do enjoy working with the doctoral students! Daniela Panáková: There are not so very many women group leaders at MDC, but ever more women in science. That’s why I think it’s important to have an ombudswoman. I was surprised about the result of the election. I’m really pleased and feel very honoured. I shall do the best I possibly can and certainly take the job seriously.

Happiness comes from the heart, advises renowned scientist Gottfried ‘Jeff ’ Schatz.

‘Follow Your Heart!’ Renowned Biochemist Got t f ried ‘Jef f ’ Schat z addressed the brand new postdocs at MDC's first PhD graduation ceremony. Among them wa s Kristin Pet zold, who repor ts on the festivities for the imdc.

Nadine Richter, Cornelia Hainer

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lmost four years ago, as my supervisor's first doctoral candidate, I joined an almost empty lab. Our work group subsequently grew, as did our equipment and with it, my understanding of embryonic pancreatic development. Now my dissertation has been written, defended and published. Even though the path was not always easy, I learned a lot. Concluding this exciting time as a

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doctoral candidate definitely deserved to be recognised with a fine ceremony. I got together with the coordinators of the MDC Graduate Schools Jana Dröse, Michaela Herzig, Sabine Löwer and Annette Schledz, as well as the PhD candidates Amal Alami and Douaa Mugahid, for a brainstorming on the kind of event we wanted. Together we organised MDC's first ever PhD graduation ceremony, held on 7 December 2012. MDC's Scientific Director Walther Rosenthal and his deputy Thomas Sommer opened the hour-long ceremony with a welcoming speech. They congratulated the successful graduates and wished them every success for the next stage of their careers. This was followed by an address by the keynote speaker, award-winning, eloquent Gottfried “Jeff” Schatz, which was the highlight of the ceremony, not only for me. The Biochemist amusingly and critically presented his view of science and scientists: According to Jeff, scientists do not concern themselves with the known, but with the unknown: a scientist was never content with existing dogma but always tried to question it, only to raise even more questions once the old ones had been answered. “Follow your heart!” said Jeff. While ambition and the willingness to work hard might lead to future success, only our hearts could tell us which decisions would make us happy. Thunderous applause followed Jeff's speech, and then the twenty graduates were asked to come on stage. In addition to their doctoral certificates, which they received from the hands of the Graduate School Directors Achim Leutz, Gary Lewin, Michael Gotthardt and Salim Seyfried, the young researchers were also presented with a personally autographed collection of Jeff's essays. A champagne reception with delicious pastries and a cake in the shape of a doctoral cap closed the festivities. Those present could also vote for the most attractive doctoral cap from amongst the graduates’ personal photographs taken on the day of their doctoral defence. The prize, the new

Photos: David Ausserhofer

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PhD cartoon calendar by Jorge Cham, went to the Hübner working group, which had made a multicoloured cap adorned with Eppendorf tubes for their PhD candidate Katharina Grunz. All the graduates and guests were delighted with this first graduation ceremony. For me, personally, it was a wonderful way to mark the end of my time as a PhD student at MDC. The next graduation ceremony will be held on 6 December 2013. Register at the Graduate Office – they are looking forward to receiving your ideas.

A PhD in your pocket and your eye on the future

Kristin Petzold

Not only the most beautiful, but also the most opulent academic's mortarboard: Graduate Katharina Grunz.

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Campus

Campus

‘Trainee

missing.

Are we under thre at from magnetic chaos? ’ Comic ar t in architecture tells an ama zing stor y

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trainee climbs into an MRI scanner and disappears without trace. The scientists at the institute try to find him. They repeat the experiment using a rat. That disappears, too. It transpires that people frequently go missing in the scanner. The public are getting suspicious, families start making enquiries, the media are scrambling to get the story. Headlines in one of the tabloids read: ‘Trainee missing. Are we under threat from magnetic chaos?’

Photos: Robert Patz, Aljoscha Redenius

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If you think that is impossible, just take a look inside the MRI building on campus. In the ‘miracle box’ we presented in the first edition of our staff magazine imdc another miracle has occurred: last year, a floor to ceiling, 155 metre long wall comic appeared over three storeys telling the tale of the trainee, Felix Lehmann. Berlin artist, Robert Patz, won the Art in Architecture Competition for the Berlin Ultrahigh Field Facility (B.U.F.F.) and

Campus

printed on individual lengths of wallpaper which cover the entire surface of the hallways, including images of doors and corners as well as structural elements like radiators. The artist’s (and, indeed, MDC’s) decision to choose wallpaper as the medium for this piece of art in architecture was both unusual and logical: it means that the art and the architecture are inextricably bonded. But there are limits to fusion: health and safety prevented the fire alarms from being integrated in the visual layout. They now have a life of their own on the walls – just like the trainee, Felix Lehmann. vg

completed his creation for the research building in spring 2012. The graphic novel, called “Side Effects”, plays on the fears and sci-fi visions of teleportation experienced by quite a few patients having an MRI scan. And it tells how the research world might react to such unexpected events. In “Side Effects” Patz conjours an aesthetic relationship on several different levels between content and the location for which he created his work of art.

The comic’s visual language is stylised and consistent with the technological environment. The discreet colouring, in grey and mellow orange tones, respects the fact that the piece is part of a working area used by patients and employees. B.U.F.F.’s technical rooms and labs are unmistakable; the story is set in the machine right in front of the observer’s eyes. In his choice of material, Patz also managed to fuse location and work of art. The comic is

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imdc04 March 2013

English