Giulio Superti-Furga, Scientific Director of CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and Professor for Medical Systems Biology of the Medical University of Vienna has been appointed Member of the Scientific Council of the ERC, on the 10th anniversary of its existence, for a function period of 4 years.
The European Research Council is the most important and prestigious funding institution for basic research in any field conducted within the European Union. Excellence is the sole criterion for selection; there are neither thematic priorities, nor geographical or other quotas for funding. Perhaps the most important funding programme of the ERC is the ERC Starting Independent Research Grant, promoting early scientific independence of promising talents with 2 million Euros over a period of 5 years. It has created a very positive impact on the attractiveness of Europe as research area. But the ERC has also other programmes, such as the ERC Advanced Investigator Grant, which fosters innovation carried out by established scientists with a proven scientific track record of excellence. Having been awarded two ERC Advanced Investigator Grants over the years and two ERC Proof-of-Concept Grants, to explore the application potential of research ideas, Giulio Superti-Furga, who also acted as ERC panel member in the past, knows the ERC well and is well suited to offer his experience to the organization that this year celebrates its 10th anniversary.
The ERC is governed by the Scientific Council, consisting of eminent European scientists and scholars including Nobel Prize laureates. Members are nominated by an independent search committee and appointed by the European Commission. Since 2014 Professor Jean-Pierre Bourguignon, a renowned French mathematician, is President of the European Research Council. From 2010 to 2013 Professor Helga Nowotny, a Viennese Professor of Social Studies of Science held this prestigious position. She was also a founding member of the ERC in 2007. In 2017 the European Research Council is celebrating its 10th anniversary.
The ERC Scientific Council acts on behalf of the scientific community in Europe to promote creativity and innovative research. Giulio Superti-Furga: “It is a great honor to accept this important responsibility, which has had a tremendously positive impact on basic research in Europe. My aspiration is to contribute to a more science and innovation-friendly climate in Europe by promoting excellence in research and ensuring that politicians protect and promote the ERC as the most successful research funding scheme of the EU. Results from basic research accompany us at every step and should therefore become a core theme in everyday life - in education, in the media and in public discussions. Society and politics must have the courage to invest in new projects, to keep pace with scientific developments and associated implications. It is important to understand science as a fundamental component of our culture and of our future and a motor for innovation and competiveness also for the European industry."
CeMM Adjunct PI Thijn Brummelkamp and his team discovered a surprising role of a host enzyme in Picornavirus life cycle. Their study, published in Nature, offers a completely new approach for antiviral therapies, which are soon anticipated to enter preclinical development.
Polio, hepatitis A, but also the common cold – Picornaviruses cause a broad range of human diseases. Their structural and genetic diversity made it difficult to develop effective antiviral therapies against this large family of viruses. Lacking the membrane envelope present in other types of viruses, Picornaviruses have developed a sophisticated – and largely unknown – mechanism to safely deliver their RNA packaged into protein shells called capsids into the cytoplasm of their host cells.
In this crucial step of Picornavirus infection, CeMM Adjunct Faculty Member Thijn Brummelkamp, group leader at CeMM’s EU-Life partner institute NKI, and his team identified a hitherto unknown and surprising role of a protein called PLA2G16: Located at the host’s cell membranes, PLA2G16 is essential for poliovirus entry, acting at a previously unknown step between pore formation and translation of viral RNA (published in Nature, doi:10.1038/nature21032).
The scientists didn´t leave it with that: Cells in which the PLA2G16 gene was deleted were resistant to virus infection, and mice lacking the gene were protected from a dose of a virus that would normally be lethal. Inhibition of the drugable PLA2G16 Protein surrenders picornavirus particles to a clearance mechanism normally associated with bacterial infections.
“These findings suggest that PLA2G16 can be exploited as novel antiviral target for diseases caused by picornaviruses. Furthermore, as such drugs would target a host factor rather than a viral protein, there would be a high barrier for the virus to develop drug resistance”, explains Dr Thijn Brummelkamp.
The CeMM spin-off company Haplogen, of which three CeMM faculty members were scientific founders, is developing drugs targeting PLA2G16 in partnership with Evotec which are anticipated to enter pre-clinical development in the course of 2017.
Jacqueline Staring, Eleonore von Castelmur, Vincent A. Blomen, Lisa G. van den Hengel, Markus Brockmann, Jim Baggen, Hendrik Jan Thibaut, Joppe Nieuwenhuis, Hans Janssen, Frank J. M. van Kuppeveld, Anastassis Perrakis, Jan E. Carette & Thijn R. Brummelkamp. PLA2G16 represents a switch between entry and clearance of Picornaviridae. Nature, Jan 2016. DOI: 10.1038/nature21032.
This work was partially funded by the Swiss National Science Foundation (SNF), the Cancer Genomics Center (CGC), the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NOW) and the European Research Council (ERC).
Diet-related diseases like non-alcoholic fatty liver disease (NAFLD) are known to have a major inflammatory component. However, the molecular pathways linking diet-induced changes with inflammation remained elusive. In a new study, Christoph Binder’s Group at CeMM and the Medical University of Vienna identified crucial inflammatory processes in NAFLD and found that malondialdehyde (MDA), a biomarker for oxidative stress, plays a key role in the development of NAFLD and can be neutralized by specific natural antibodies – a novel approach towards a potential therapy for the prevalent disease.
Worldwide, the incidences of obesity, hypertension or insulin resistance are alarmingly high. As a consequence, risk of developing inflammation-associated diseases like type 2 diabetes, NAFLD and cardiovascular disease increased accordingly. However, the exact pathways that link the eating habits with the ensuing inflammation were so far not well understood.
The team of Christoph Binder, Professor of Atherosclerosis Research at the Medical University of Vienna and Principal Investigator at CeMM, in collaboration with Ronit Shiri-Sverdlov at the Maastricht University, Christoph Reinhardt at the University Medical Center of the Johannes Gutenberg University Mainz and the German Center for Cardiovascular Research Mainz was not only able to shed light on the biological processes that lead to the development of chronic inflammation upon a nutrient rich diet in mice. Moreover, the Scientist found MDA to be a key player in hepatic inflammation which can be neutralized with natural antibodies. Their results were published in Hepatology (DOI: 10.1002/hep.28970). Shared co-first authors of the study are Clara Jana-Lui Busch, PhD Student at CeMM and the Medical University of Vienna, and Tim Hendrikx, PostDoc in the group of Christoph Binder.
“This study shows how the close collaboration of CeMM and the Medical University Vienna fosters the development of a future precision medicine”, says senior author Christoph Binder. “With cutting edge RNA sequencing methods and bioinformatic analyses of transcriptome data, we discovered key mechanisms in some of the most prevalent diseases and we confirmed those findings in mice models.” Binder explains, and adds: “Above that, the administration of specific antibodies for MDA epitopes provide a promising new approach for the development of therapeutic strategies.”
Clara Jana-Lui Busch*, Tim Hendrikx*, David Weismann, Sven Jäckel, Sofie M. A. Walenbergh, André F. Rendeiro, Juliane Weißer, Florian Puhm, Anastasiya Hladik, Laura Göderle, Nikolina Papac-Milicevic, Gerald Haas, Vincent Millischer, Saravanan Subramaniam, Sylvia Knapp, Keiryn L. Bennett, Christoph Bock, Christoph Reinhardt, Ronit Shiri-Sverdlov and Christoph J. Binder (*shared first author). Malondialdehyde epitopes are sterile mediators of hepatic inflammation in hypercholesterolemic mice. Hepatology, Dec 16 2016. DOI: 10.1002/hep.28970
This study was supported by the Austrian Science Fund (FWF, SFB Lipotox F30), Boehringer Ingelheim (PhD Fellowship), Austrian Academy of Sciences (Doc Fellowship), EMBO (Short Term Fellowships), The Netherlands Organisation for Scientific Research (NWO), German Center for Cardiovascular Research (DZHK), German Federal Ministry of Education and Research, and the German Research Foundation (DFG).
The next PhD Program at CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, in Vienna, starts in October 2017. We are looking for exceptionally motivated PhD candidates with a keen interest in genomics, medicine and working in teams and have 15 fully funded positions to offer.
The 2017 CeMM PhD Program will focus on the thematic areas: Infection, Immunity, Metabolism, Cancer and Network Medicine. These areas are built on the pillars of epigenetics, bioinformatics and systems biology, chemical biology and the mechanism of action of drugs, high-throughput genetics, genomics and proteomics, and molecular and cell biology.
The successful candidate will be awarded a generous scholarship which will cover all research costs, university fees, work-related travel, salary and health insurance for 4 years. The degree will be awarded by the Medical University of Vienna.
How to Apply
To be eligible to enroll in the CeMM PhD Program all candidates are required to have a final degree* in medicine, biology, chemistry, bioinformatics, computer science, engineering, physics, mathematics or a similar subject (*at least a four year Bachelor’s degree). The working language at CeMM is English, so excellent written and oral communication skills in English are also required.
Apply now! The application deadline is 10th February 2017.
For further information on the PhD Program, and to apply through the online system please visit www.cemm.at/phd-program
QIAGEN announced the European launch of a unique calreticulin (CALR) mutation assay to aid in establishing the diagnosis of myeloproliferative neoplasms (MPN)
The importance of CALR mutations in MPN was first described in December 2013 by the group of CeMM Principal Investigator Robert Kralovics. In April 2014 QIAGEN obtained the exclusive worldwide license rights to intellectual property and know-how from CeMM covering specific mutant alleles of the CALR gene.
QIAGEN’s new ipsogen CALR RGQ PCR Kit (ipsogen CALR assay) has been developed for the detection of CALR mutations in genomic DNA from patients which are suspected of MPN. It enables the identification of the two major types of CALR mutations and detects additional mutations in specific areas of this disease-relevant gene.
MPN are a group of blood cancers characterized by significant symptoms and complications such as thrombosis and a high risk of transformation into acute leukemia. The different forms of MPN combined affect nearly 250.000 patients in Europe and 300.000 patients in the US and roughly 2.5 in every 100.000 worldwide.
As the mission of CeMM is to achieve maximum scientific innovation in molecular medicine to improve healthcare, we are happy to see this novel diagnostic tool for a widespread blood disorder being introduced into practice by one of the leading companies for biomedical technologies.
Publication: Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant'Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schönegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013 Dec 19;369(25):2379-90.
A subset of lung tumours is exquisitely sensitive to a class of recently approved anti-cancer drugs. Researchers at the CeMM and the Ludwig Institute for Cancer Research in Oxford published this finding in the journal Nature Communications. It opens the way for new clinical trials in a type of cancer considered to be “undruggable” and may lead to a therapy for up to 10% of lung cancer patients.
About 10% of lung tumours carry mutations in a gene called ATM. However, there are no drugs available in the clinic to treat ATM mutant lung cancer. With cutting edge high-throughput drug screens, the team of Sebastian Nijman, CeMM Adjunct PI and Group Leader at the Ludwig Institute for Cancer Research in Oxford made a surprising discovery: Cancer cells with ATM mutations are sensitive for drugs that inhibit an enzyme called MEK. The study was published in Nature Communications (DOI: 10.1038/NCOMMS13701)
In ATM deficient lung cancer cells, Nijman’s team found that MEK inhibition results in cells being unable to keep proliferating and leads to apoptosis. An unexpected finding, as MEK inhibitors have so far been approved for the treatment of a type of skin cancer but not for lung cancer.
The study constitutes a substantial contribution for the development of a future precision medicine: ATM mutations could be used as a potential biomarker to stratify lung cancer patients to receive a MEK inhibitor. Given that lung adenocarcinomas are among the most prevalent types of tumours for both men and women worldwide, a significant number of patients could benefit from a MEK inhibitor based treatment.
Michal Smida*, Ferran Fece de la Cruz*, Claudia Kerzendorfer, Iris Z Uras, Barbara Mair, Abdel Mazouzi, Tereza Suchankova, Tomasz Konopka, Amanda M Katz, Keren Paz, Katalin Nagy-Bojarszky, Markus K Muellner, Zsuzanna Bago-Horvath, Eric B Haura, Joanna I Loizou and Sebastian MB Nijman (* equal contribution). MEK inhibitors block growth of lung tumors with mutations in Ataxia Telangiectasia Mutated. Nature Communications, 2016. DOI:10.1038/NCOMMS13701.
This study was supported by the European Research Council (ERC), the Moffitt Lung Cancer Center of Excellence, research grants from the Austrian Science Fund (FWF), the Vienna Science and Technology Fund (WWTF) and the European Union FP7 Career Integration Grant, fellowships from the Austrian Academy of Sciences as well as by the Ministry of Education, Youth and Sports of the Czech Republic.
FDA-approved artemisinins, since decades used to treat malaria, transform glucagon-producing alpha cells in the pancreas into insulin producing cells – thereby acquiring features of beta cells, the cell type damaged in type 1 diabetes. Those groundbreaking results, published in Cell, provides the basis for a promising new approach towards a cure for type 1 diabetes.
For years, researchers around the globe tried various approaches with stem- or adult cells in order to replace destroyed beta-cells in the bodies of diabetes patients with newly-produced insulin-secreting cells. Now a research team coordinated by Stefan Kubicek, Group Leader at CeMM, eventually got a lead: In their latest study, published in Cell (DOI: 10.1016/j.cell.2016.11.010), they showed that malaria drug artemisinin hit the bulls eye.
“With our study, we could show that artemisinins change the epigenetic program of glucagon-producing alpha cells and induce profound alterations of their biochemical function”, Stefan Kubicek explains. The epigenetic master regulator Arx was identified as the key molecular player in the transformation process. “Arx regulates many genes that are crucial for the functionality of an alpha cell,” says Stefan Kubicek. Together with the group of Jacob Hecksher-Sorensen at Novo Nordisk, Kubicek’s team proved that Arx is sufficient to confer alpha cell identity and does not depend on the body’s influence.
In addition, Stefan Kubicek´s team and their collaborators (Martin Distel, CCRI Wien; Dirk Meyer, Leopold-Franzens-Universität Innsbruck; Patrick Collombat, INSERM Nice; Physiogenex, Labege) observed an increased beta cell mass and improved blood sugar homeostasis in diabetic zebrafish, mice and rats upon artemisinin delivery. As the molecular targets for artemisinins in fish, rodents and humans are very similar, chances are high that the effect on alpha cells will also occur in humans.
Jin Li, Tamara Casteels, Thomas Frogne, Camilla Ingvorsen, Christian Honoré, Monica Courtney, Kilian V.M. Huber, Nicole Schmitner, Robin A. Kimmel, Roman A. Romanov, Caterina Sturtzel, Charles-Hugues Lardeau, Johanna Klughammer, Matthias Farlik, Sara Sdelci, Andhira Vieira, Fabio Avolio, Francois Briand, Igor Baburin, Peter Májek, Florian M. Pauler, Thomas Penz, Alexey Stukalov, Manuela Gridling, Katja Parapatics, Charlotte Barbieux, Ekaterine Berishvili, Andreas Spittler, Jacques Colinge, Keiryn L. Bennett, Steffen Hering, Thierry Sulpice, Christoph Bock, Martin Distel, Tibor Harkany, Dirk Meyer, Giulio Superti-Furga, Patrick Collombat, Jacob Hecksher-Sørensen, and Stefan Kubicek. Artemisinins Target GABAA Receptor Signaling and Impair α Cell Identity, Cell 2016. DOI:10.1016/j.cell.2016.11.010.
This work was partially funded by the Juvenile Diabetes Research Foundation (JDRF), the European Research Council (ERC), the Medical University of Vienna, the European Molecular Biology Organization (EMBO), the NovoNordisk Foundation, the European Commission FP7 Marie Skłodowska-Curie Actions, the Austrian Science Fund (FWF), the Austrian Academy of Sciences (ÖAW); the INSERM AVENIR program; the INSERM, the FMR, the ANR/BMBF, LABEX SIGNALIFE, the Max- Planck Society, Club Isatis, Mr. and Mrs. Dorato, Mr. and Mrs. Peter de Marffy-Mantuano, the Fondation Générale de Santé and the Foundation Schlumberger pour l’Education et la Recherche.
The Austrian Federal Ministry of Science, Research and Economy (BMWFW) presented the future strategy for the Austrian Life Science and Pharmaceutical Sector at CeMM
It was an honor for CeMM to host State Secretary Dr. Harald Mahrer with his delegation for a press conference to present a strategy document on the Austrian Life Science and Pharmaceutical Sector.
CeMM is enthusiastic about the fact that life sciences have become a strategic focus point for the Federal Ministry of Science, Research and Economy, and appreciates the commitment to bring Austria among the Top 3 performers in Europe according to a number of parameters. The overall goal of the strategy is to position Austria among the innovation leaders, and to also show the positive economical and societal effect of life science research and the pharmaceutical sector in general. CeMM Director Prof. Giulio Superti-Furga pointed out during the press conference that the number of ERC projects granted to scientists in Austria within the last 3 years is already an impressive sign of the vitality of Austria’s life science research and a very good indicator for the further potential of our country in the future, demonstrating that Austria can compete on an international level.
Among the priorities for the future mentioned by State Secretary Dr. Mahrer in the life sciences, there are: basic research, state-of-the-art infrastructure, personalized medicine, clinical research, big data management, translational efforts, and a better dialogue between science and society. CeMM is very proud to be able to claim that it is already doing pioneering work in most of these fields, and that everybody at CeMM is further committed to do everything possible to make sure that the life science strategy becomes a successful endeavor and creates an important impact.
Link to BMWFW Strategy Document: www.bmwfw.gv.at/Presse/Documents/Life_Science_Strategie_barrierefrei.pdf
The sequencing of the human genome was a milestone for biology and medicine – but not all is written in our genes. Scientists are now presenting a second chapter of the book of life: Over the last five years, a worldwide consortium of scientists has established epigenetic maps of 2,100 cell types. Within this coordinated effort, CeMM contributed detailed DNA methylation maps of the developing blood, opening up new perspectives for the understanding and treatment of leukemia and immune diseases.
The identity of each cell type is largely defined by an instructive layer of molecular annotations on top of the genome – the epigenome – which acts as a blueprint unique to each cell type and developmental stage. Unlike the genome the epigenome changes as cells develop and in response to changes in the environment. Defects in the epigenetic blueprint are involved in many diseases.
A collection of 41 coordinated papers now published by scientists from across the International Human Epigenome Consortium (IHEC) sheds light on these processes. Three of these papers have been coordinated by Christoph Bock at CeMM. The latest study from Christoph Bock’s team, published today in the journal “Cell Stem Cell”, charts the epigenetic landscape of DNA methylation in human blood.
Led by CeMM scientists Matthias Farlik and Florian Halbritter together with Fabian Müller from Max Plank Institute for Informatics, this study highlights the dynamic nature of the epigenome in the development of human blood. Using the latest sequencing and epigenome mapping technology, Bock’s team now unraveled a blueprint of blood development that is encoded in the DNA methylation patterns of blood stem cells and their differentiating progeny. The result is a detailed map of the human epigenome, similar to a three-dimensional mountain landscape.
Certain routes of differentiation are jammed in leukemia, such that cells can no longer reach their destination and take wrong turns instead. Surveillance of those cells by epigenetic tests can contribute to a more precise diagnosis of leukemia – clinical tests of this approach are ongoing. „The epigenetic map of the human blood helps us understand how leukemia develops and which cells drive the disease” says Christoph Bock.
Matthias Farlik, Florian Halbritter, Fabian Müller, Fizzah A. Choudry, Peter Ebert, Johanna Klughammer, Samantha Farrow, Antonella Santoro, Valerio Ciaurro, Anthony Mathur, Rakesh Uppal, Hendrik G. Stunnenberg, Willem H. Ouwehand, Elisa Laurenti, Thomas Lengauer, Mattia Frontini, and Christoph Bock. DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation, Cell Stem Cell, 2016. DOI:10.1016/j.stem.2016.10.019
This study was partly funded by the BLUEPRINT Project of the European Union.
This year´s S.M.A.R.T. Lecture was a truly exceptional experience for the audience: Mathieu Ossendrijver, professor for the history of ancient science at the Humboldt University in Berlin, presented his findings on astronomic calculations of ancient Babylonians in our fully booked lecture hall.
From five cuneiform tablets, dating from 350 to 50 BCE, Ossendrijver decrypted a sophisticated calculation method to determine and predict Jupiter’s position. According to his findings, more than two thousand years ago the Babylonian astronomers were able to compute a body´s displacement as an area in time-velocity space – a mathematical operation that was hitherto thought to be invented only in the middle ages.
Ossendrijver’s discovery was a true sensation – when he published his findings in Science, it not only astonished his colleagues, but found a broad resonance all over the world. His work changed the view on ancient Babylonian astronomy, and above that, it showed that their mathematical skills might even have had an unprecedented impact on Greek mathematicians and their successors.
The lecture was followed by a lively and fruitful discussion that continued at the subsequent reception – it rounded up this wonderful and enlightening evening. Our warmest thanks to Mathieu Ossendrijver´s for a magnificent and memorable S.M.A.R.T. Lecture!