On September 29, 2017, the CeMM members went on the annual outing of the institute, to start the academic year with a community experience, to strengthen the relationships with colleagues, and to broaden our horizon. This year, we visited Göttweig Abby and the Schallaburg, both spectacular historic sites in a picturesque landscape.
On perfect weather, the trip started with a visit of Göttweig Abby, also known as “Lower Austria´s Montecassino” for its beautiful location on top of a hill. The Benedictine monastery, founded in the 11th century, is full of valuable collections of religious engravings, coins, antiquities and musical manuscripts, and its architectural features are ranging from Romanesque to Baroque. The imperial wing with its sumptuous furnishings and exquisite (ceiling-) paintings left a strong impression.
The second part of the outing brought us to the Schallaburg, where an exhibition on Islam in Austria provided background knowledge and facts, but also new perspectives and food for thought. Where do cultures and religions meet? Where does diversity give rise to fear, where is it felt to be a threat? CeMM is grateful to Professor emeritus Bert Fragner, expert in Islamic and Iranian Studies, who accompanied us and explained how the Islam and Muslim cultures belong to Austria and its society since centuries.
On September 28, 2017, Christiane Druml, Director of the Josephinum of the Medical University of Vienna, Curator Moritz Stipsicz, and CeMM Director Giulio Superti-Furga invited to a journey to the very heart of the interface of art and science. On the occasion of the exhibition “Artificial Hearts – The Bridge to Survival” in the Josephinum, a motley audience of artists, physicians, scientists and students visited the astonishing collection of historic medical exhibits and contemporary art pieces and installations, followed by a lively discussion round in CeMM´s Brain Lounge.
Vienna has played a pioneering role in the development of the artificial hearts. It was preceded by decades of extraordinary research achievements, which are showcased at the Josephinum. Interventions by artists Judith Fegerl, Peter Garmusch, Stephanie Pflaum, Samuel Schaab and Anna Witt complement the historic collection of instruments and anatomical wax models and created an extraordinary experience, taking the guests in unexpected audio-visual spheres and blurring the lines between art and science.
The audience then moved on to an open discussion round in the CeMM Brain Lounge, where the effects of increasing isolationism and nationalism on art and science was debated. Does oppression and restriction increase the motivation and creativity of artists and scientists? What is necessary to mount resistance and form opposition? What kind of influence, both societal and economical, do art and science have? What are the different financial needs and dependencies, and how do they influence the ability to oppose and provoke?
Giulio Superti-Furga (moderator), Christiane Druml, Moritz Stipsicz, artist and researcher Anna Artaker, visual artist Roswitha Schuller, print journalist Almuth Spiegler, artist Hubert Scheibl, radio journalist Elisabeth Nöstlinger, Oscar Bronner, founder of the journals Trend and Profil and editor of Der Standard, MedUni Vienna Professor Michael Trauner, and CeMM PI´s Christoph Bock and Jörg Menche opened the discussion with their experiences and thoughts. The evening ended at CeMM´s terrace with hour-long conversations. We want to thank everybody who contributed to this most pleasant, and inspiring evening.
CeMM is member of EU-LIFE (www.eu-life.eu). EU-LIFE is a European alliance of research centers of excellence in life sciences, whose mission is to support and strengthen European research excellence. Representing over 7,200 scientists and staff distributed in more than 500 research groups across Europe, EU-LIFE is a strong representative of the scientific community throughout Europe.
In a position paper we announce our key priorities for the next Framework Program for Research and Development (FP9) that will run from 2021 to 2027, which can be summarized as follows:
• To double the investment by the European Commission to 150 billion euro for the entire programme 2021-2027. It is clear from calculations for previous framework programs by the European Commission that every euro spent will generate a multiple in economic benefits over time.
• To invest more in basic research than today. Without basic research, no applied research is possible. Good basic research actually acts as a booster for applied and commercial research investments.
• To encourage collaboration of excellent research based on more bottom-up, non-prescriptive approaches that address key societal challenges.
• To encourage technology transfer that turns scientific insights into economic value. Technology transfer is critical to counter the current “innovation paradox”. The true challenge is to pro-actively assist the basic researchers with identifying and enabling commercial and medical use of their findings.
• To have excellence as the sole criterion for selection in FP9.
• To focus on open science in order to foster wider impact of excellent research. Furthermore, expected timing of impact of research outputs should be readjusted for the longer term.
Jo Bury, Chairman of EU-LIFE and Managing Director of the Flanders Institute of Biotechnology (VIB): “Excellent science and professional technology transfer are essential for the well-being of citizens in the future. We have seen that some approaches were successful in the past, where deep scientific insights have led to major breakthroughs in applied science as we see today in immuno-oncology for instance. In our research institutes, tens of thousands of Europe’s leading researchers are committed to finding solutions for the most challenging issues of our time, both in health and agriculture. For public research institutes, the funding by the Framework Programs is critical. We are convinced that the right choices will be made to re-balance the funding for more basic research”.
As a leading research institute in Austria we look forward to boost national, regional and European research and innovation.
Blistered dancing feet, tissues wet with tears of joy and the taste of cake still on our lips: the 10th anniversary celebration on September 12, 2017 at the Aula der Wissenschaften was CeMM´s biggest, most spectacular and memorable event we had since the opening of our research building.
We thank everybody who celebrated with us and who contributed to the success of CeMM over the past years! It is your support and friendship that motivates us to do the best possible research.
Exhausted but happy, we summarize CeMM´s decennial jubilee as follows: Moderator Annie Kay wonderfully guided the audience through a mixture of overwhelming light and video shows, scientific highlights, guests of honor, musical delights, heartwarming wishes, astonishing theatre and many other special features.
“If I have to summarize what CeMM has done to the city and the community in one word, I would say “inspirational” said Andreas Mailath-Pokorny, city council for culture, science and sport of Vienna.
Together with Helga Nowotny, former President of the ERC, Markus Müller, Rector of the Medical University of Vienna, Klement Tockner, President of the FWF, Thomas Henzinger, President of the Institute of Science and Technology Austria, and Jo Bury, Chair of EU-LIFE and Managing Director of the Flanders Institute of Biotechnology, Andreas Mailath-Pokorny took part in a quiz game moderated by CeMM PhD-Student Martin Moder, that playfully highlighted the importance of funding for research. Markus Müller compared the close collaboration of the Medical University of Vienna with CeMM with a happy marriage that he wishes to continue until the end of their days.
Jo Bury held the keynote speech, presenting in his talk CeMM´s ranking in international comparison as well as its role in the EU-Life consortium, an alliance of top research centers created to build and promote excellence in life sciences in Europe.
From the very beginning of the ceremonial act, members of the Vienna English Theater “Walking Acts” accompanied the guests and introduced with their characters the main research fields of CeMM. Miss DNA, Monsieur Macrophage, Cancer, Bloody Lady, Dame Virus and Mr. Molecule later showed their exquisite art of acting during a short scripted piece on stage, but also supported the whole event with their entertaining impro theatre roles.
With mind-blowing visual effects digitally mapped over the entire festive hall, the light art collective Lichttapete, headed by Marcus Zobl, accentuated each and every part of the evening programme. Alma, a sublime ensemble of accordion, violin and double bass, who charmed with their winking nod to traditional Austrian folk music, set the musical framework during the celebration act. Subsequently, the world-famous Irish folk band The Dublin Legends brought guests and CeMM employees to hit the dancefloor, where they stayed until late at night dancing to the lineup of DJane Alexandra Augustin.
We are grateful to Bertram Schütz from Science Communications who helped CeMM organize the event, and to Kriso Leinfellner, Stefanie Lichtwitz and their team for the exhibition designs of the evening and for being a valuable partner for CeMM from the very beginning.
Last but not least, we thank everyone who contributed to the blue book photo challenge. We will show the winners of each categories, and a selection of the most creative pictures on the upcoming weeks on Facebook.
CeMM today officially announces the start of operation of a new spin-off company, Allcyte, founded by CeMM Director Giulio Superti-Furga, Berend Snijder, now Professor at the ETH Zurich, Gregory Vladimer, and Nikolaus Krall. The team met while Snijder, Vladimer, Krall were postdoctoral fellows in the research group of Giulio Superti-Furga. Allcyte supports pre-clinical drug development and clinical decision making services by helping physicians find the right drug for the right patients, and pharmaceutical companies identify the most promising indications for their drugs and drug candidates. In the era of big-data medicine, Allcyte is built around the “Pharmacoscopy” high-content imaging platform originally developed at CeMM, and clinically validated in collaboration with the Department of Hematology of the Medical University of Vienna. The Pharmacoscopy technology is the basis for a number of academic research collaborations between CeMM and the MedUni Wien, including a life science grant provided by the WWTF that aims to define better personalized medicine for late-stage hematological cancer patients.
As of September 1, Allcyte has entered an important strategic collaboration with Boehringer Ingelheim to advance Boehringer Ingelheim’s preclinical oncology drug discovery by using the pharmacoscopy technology. Pharmacoscopy enables the profiling of drug response in primary liquid patient samples with minimal sample requirement, high speed, and with single cell resolution, enabling never-before-quantified phenotypes to drive scientific exploration. The platform can not only measure cell-autonomous drug effects (e.g., specific killing of a particular cell) but is also capable of quantifying the interplay between different cell types in complex human tissues by measuring physical cell-cell interactions in an unprecedented and statistically robust manner. Parts of the technology have recently been published in Vladimer et al Nature Chemical Biology 2017.
The mission of CeMM is to achieve maximum scientific innovation in molecular medicine by performing excellent research. Only the efficient commercialization of CeMM’s proprietary and ideas can lead to the improvement of healthcare. Therefore intellectual property of CeMM already resulted in the founding of new start-up companies (Haplogen, MyeloPro, Allcyte), and into out-licensing of patents or partnerships with industry involving consultancy, know-how, technology transfer.
Allcyte is supported by Austrian Business Agency (AWS) pre-seed and seed grants managed by the Federal Ministry of Science, Research and the Economy, and the Federal Ministry for Transport, Innovation and Technology, as well as by private investors and industry cooperation.
Every tissue has its own pattern of active alleles (the gene variants inherited from the mother or father),. For the first time, scientists were able to show that the differential allele activity is regulated by tissue-specific, regulatory DNA elements known as enhancers – a process that could also be involved in many diseases. The results of the former CeMM group of Denise Barlow were published in the high-profile open access journal eLife.
Every gene in (almost) every cell of the body is present in two variants – so called alleles: one is deriving from the mother, the other one from the father. In most cases both alleles are active and transcribed by the cells into an RNA message. However, for a few genes, only one allele is expressed, while the other one is silenced. For long it was thought that the pattern of active alleles is nearly homogeneous in the various tissues of the organism.
The new study (DOI:10.7554/eLife.25125), where CeMM PhD Student Daniel Andergassen is first author (now a PostDoc at Harvard University), uncovers a different picture. By performing the first comprehensive analysis of all active alleles in 23 different tissues and developmental stages of mice, the team of scientists revealed that each tissue showed a specific distribution of active alleles. The scientists were able to catalogue active alleles in a comprehensive set of mouse tissues, or the mouse “Allelome”, and gain an insight into how this differential gene activity is regulated.
The scientists found that both genetic and epigenetic differences between the maternal and paternal allele contributed to the observed tissue-specific activity patterns. This study reveals for the first time a comprehensive picture of all active alleles in different tissues. The results are not only valuable to understand basic biological functions, but will also help investigating diseases that involve defective gene regulators.
Interestingly, this study demonstrated that Igfr2, the first imprinted gene discovered by Denise Barlow in 1991, is surrounding by a large cluster of imprinted genes that extend over 10% of the chromosome, making it the largest co-regulated domain in the genome outside of the X chromosome. Fittingly, after her lab found the first imprinted gene, and discovered the first imprinted non-coding RNA shown to control imprinted silencing, the final work from Denise Barlow’s lab as she went into retirement reveals the full picture of imprinted genes in the mouse.
Daniel Andergassen, Christoph P Dotter, Daniel Wenzel, Verena Sigl, Philipp C Bammer, Markus Muckenhuber, Daniela Mayer, Tomasz M Kulinski, Hans-Christian Theussl, Josef M Penninger, Christoph Bock, Denise P Barlow, Florian M Pauler, Quanah J Hudson. Mapping the mouse Allelome reveals tissue-specific regulation of allelic expression. eLife, August 14, 2017. DOI:10.7554/eLife.25125
This study was supported by the Austrian Science Fund FWF.
A single-gene mutation may cause a severe bowel disease in children. This could be shown in a recent study by an international research team led by Kaan Boztug at CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD) together with Michael Lenardo, National Institute of Health (NIH), Bethesda.
The newly discovered alterations lead to total loss of a protein called CD55, causing life-threatening bowel inflammation, chronic diarrhea and vascular thrombosis. The researchers unraveled the underlying molecular mechanisms and discovered previously unknown regulatory pathways relevant to bowel homeostasis. As a consequence of their findings, the researchers could identify a clinically approved drug which may specifically interfere with aberrant signaling involved in this previously unknown disease. The study, co-first-authored by Rico Chandra Ardy, has now been published in the renowned New England Journal of Medicine.
On June 7th, 2017 Giulio Superti-Furga was awarded the title of Commendatore (Commander) dell'Ordine al Merito della Repubblica Italiana (Order of Merit of the Italian Republic) by HE Giorgio Marrapodi, Ambassador of Italy.
The order was given by decree of the President of the Italian Republic Sergio Mattarella, who had visited CeMM together with Austria´s former President Heinz Fischer during his first official states visit to Austria in 2015. The Order of Merit is the highest-ranking honor system of the Italian Republic and is awarded for "merit acquired by the nation" in the fields of literature, the arts, economy, public service, and social, philanthropic and humanitarian activities and for long and conspicuous service in civilian and military careers. In his moving speech Ambassador Marrapodi emphasized the long lasting positive impression of the CeMM visit on the Italian president, the importance of science in general and the impact of the leadership and scientific achievements of Giulio Superti-Furga. The ceremony took place at the Italian Embassy in Palais Metternich under the presence of colleagues, companions, family and friends. We are very proud and congratulate Giulio Superti-Furga to this well-deserved recognition!
The CeMM Library of Unique Drugs (CLOUD) is the first condensed set of FDA-approved drugs representing the entire target and chemical space of all clinical compounds. Its potential was shown in a combinatorial high throughput screen at the CeMM chemical screening platform and published in Nature Chemical Biology: A pair of hitherto unrelated drugs proved to be highly effective against multiple prostate cancer cell lines.
(Vienna, May 22, 2017) The synergy of two combined pharmaceuticals assessed in an experimental setting can reveal completely new therapeutic options. Nevertheless, finding a novel combination of drugs for a given disease within the more than 30,000 drug products approved by the regulatory agencies was hitherto a big challenge for scientists.To facilitate systematic screening for synergistic interactions of drugs, CeMM PI Stefan Kubicek and his colleagues established a collection of 308 compounds (CeMM Library of Unique Drugs, CLOUD) that effectively represent the diversity of structures and molecular targets of all FDA-approved chemical entities.
Moreover, the scientists proved the potential of the CLOUD with CeMM´s highly automated chemical screening platform by identifying a novel synergistic effect of two drugs (flutamide and phenprocoumon (PPC)) on prostate cancer cells. The results of Kubicek´s team with Marco Licciardello as first author where published in Nature Chemical Biology (DOI:10.1038/nchembio.2382) “The combination induced massive cell death in prostate cancer cells. We then went back to the entire approved drug list, and indeed, we could show that all drugs from the clusters that flutamide and phenprocoumon represent synergize. Thereby we validated the reductionist concept underlying the CLOUD library,” Stefan Kubicek explains.
With their experiments, Kubicek´s team in collaboration with scientists from the Medical University of Vienna, the Uppsala University, Enamine Kiev and the Max Planck Institute for Informatics in Saarbrücken proved that the CLOUD is the ideal set of compounds to develop screening assays and discover new applications for approved active ingredients. At CeMM, a number of key discoveries on new applications for approved drugs have already been made with the CLOUD. Furthermore, as shown in the current issue of Nature Chemical Biology, the CLOUD is ideal for finding new drug combinations. “In view of these successes, I would predict that this set of compounds will become world standard for all screening campaigns”, Stefan Kubicek emphasizes.
Marco P Licciardello, Anna Ringler, Patrick Markt, Freya Klepsch, Charles-Hugues Lardeau, Sara Sdelci, Erika Schirghuber, André C Müller, Michael Caldera, Anja Wagner, Rebecca Herzog, Thomas Penz, Michael Schuster, Bernd Boidol, Gerhard Dürnberger, Yasin Folkvaljon, Pär Stattin, Vladimir Ivanov, Jacques Colinge, Christoph Bock, Klaus Kratochwill, Jörg Menche, Keiryn L Bennett & Stefan Kubicek. A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor. Nature Chemical Biology, May 22, 2017. DOI:10.1038/nchembio.2382
This study was supported by a Marie Curie Career Integration Grant, the Austrian Federal Ministry of Science, Research and Economy, the National Foundation for Research, Technology, and Development and the Austrian Science Fund (FWF).
The 11th CeMM Landsteiner Lecture, held by James “Jay” Bradner, President of the Novartis Institutes for BioMedical Research (NIBR) on May 15, 2017, was a truly memorable event: with enthusiasm and with great incisiveness, Dr. Bradner illustrated for the audience principles and examples of medical innovation and eloquently argued about their impact on the whole of humankind.
This year’s CeMM Landsteiner Lecture was accompanied by the wonderful accordionist Otto Lechner, whose music evoked many stimulating emotions in a short time and left the audience of more than 400 people prepared for more virtual adventures. CeMM Scientific Director Giulio Superti-Furga introduced Dr. Bradner as a pivotal figure of the chemical biology community and a visionary innovator, praising the paradigm-changing contributions of Dr. Bradner to drug discovery from a scientific and social point of view. On stage, starting with an historical overview, Dr. Bradner recalled the giants on whose shoulders every medical new modern achievement in drug discovery is built on. From vaccines to antibiotics to biomolecules like insulin – real medical progress was always achieved by radically new ideas and incisive execution.
This is also true for what regards therapy of one of the most intensively researched diseases of our time: cancer. Jay presented the highly significant progress that has been made in cancer therapy the last decades, particular by targeted therapy, exemplified by imatinib/Glivec and and T-cell-based immunotherapy, such as the one involving chimeric antigen receptors (CAR-T cells)
Jay then presented briefly the breakthrough discovery of bromo-domain inhibitors able to reprogram the transcriptional program of cancer cells, such as JQ1, from his own laboratory as associate director of the Broad’s Center for the Science of Therapeutics and as hematologist at Dana-Farber Cancer Institute. The central part of his talk dealt with a yet different, unprecedented approach able in principle to overcome the difficulty presented by so-called “undruggable” part of the human genome. If a protein is difficult to inhibit, how about taking it out of the equation altogether? In other words, to “destroy” it by a chemical strategy? The approach presented, called “targeted protein degradation”, attacks cancer proteins not by inactivating single parts of them, but by dragging them in their entirety to the garbage removal of the cell – the proteasome - where they are destroyed and recycled. Georg E. Winter, now a Principal Investigator at CeMM and present in the audience, has been critically involved in the discovery of these “degronomids” drugs while a postdoctoral fellow in the Bradner laboratory.
While other methods try to find the right key to unlock a given door shut in cancer cells, targeted protein degradation is comparable to an explosive charge that tears the door away completely – with this impressive image, Jay pointed out the game changing difference of his approach. The results of this method speak for themselves: blood cells of leukemia patients treated with JQ1-mediated targeted protein degradation seemed to have “forgotten” that they are cancer cells and thrived like healthy, normal cells again.
The last part of the talk was dedicated to the presentation of a new collaborative paradigm by which Dr. Bradner, now heading NIBR, wants to engage the scientific community. He effectively argued that by sharing tools, reagents and ambitious goals, a new era of public-private partnerships could accelerate the identification of solutions to important challenges in a manner that neither industry alone, nor academia, could achieve alone.
After his talk, Jay answered the many questions from the audience and continued the discussion at the subsequent cocktail reception, meeting literally hundreds of young as well as more senior participants and exchanging views, selfies and coordinates. We want to warmly thank Jay Bradner for his enlightening talk and this wonderful evening!