April 24, 2017

Next-Generation Microscopy with Pharmacoscopy

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A novel microscopy method, developed and patented by scientists from CeMM, allows unprecedented insights into the spatial organization and direct interactions of immune cells within blood and other liquid multi-lineage tissues. The assay, called Pharmacoscopy and published in Nature Chemical Biology, is able to determine the immunomodulatory properties of drugs within large libraries on immune cells in high resolution and high throughput. 

The search for new drugs, small molecule or biologicals, that influence the immune system in a desired manner is challenging: immune signaling, often a combination of communication via soluble proteins and direct interaction by cell-cell contacts, is subtle and hard to track in all its nuances. So far, there has been a lack of fast and robust technology to measure the effect of a potential immunomodulatory drug in particular in a cell-cell contact dimension. 

By combining state-of-the-art high-throughput fluorescent microscopy with single cell image analysis and novel analysis algorithms, Pharmacoscopy provides a powerful solution. Developed by a group of scientists at CeMM led by Director Giulio Superti-Furga and tested in collaboration with the Medical University of Vienna, Pharmacoscopy can quantify the overall spatial patterning and direct interactions of immune cells within blood with unprecedented speed and accuracy. The method was introduced in Nature Chemical Biology (DOI:10.1038/nchembio.2360).

Combined single cell resolution and fully automated platform control, Pharmacoscopy can test large drug libraries, as available in Stefan Kubicek’s PLACEBO (Platform Austria for Chemical Biology) laboratory, for compounds with immunomodulatory potential. With this method, the scientists identified Crizotinib, an FDA approved drug for non-small cell lung cancer, to have a previously unknown immunomodulatory potential.

Publication:

Gregory I. Vladimer, Berend Snijder, Nikolaus Krall, Johannes W. Bigenzahn, Kilian V.M. Huber, Charles-Hugues Lardeau, Kumar Sanjiv, Anna Ringler, Ulrika Warpman Berglund, Monika Sabler, Oscar Lopez de la Fuente, Paul Knöbl, Stefan Kubicek, Thomas Helleday, Ulrich Jäger, and Giulio Superti-Furga. Global survey of the immunomodulatory potential of common drugs. Nature Chemical Biology, April 24, 2016. DOI:10.1038/nchembio.2360

Funding: 

This study was supported by the European Research Council, the Austrian Science Fund (FWF), Swiss National Science Foundation, European Molecular Biological Organization, the Austrian Federal Ministry of Science, Research and Economy, The National Foundation for Research, Technology and Development, The Swedish Cancer Society, the Kunt and Alice Wallenberg Foundation, the Torsten and Ragnar Söderberg Foundation, and the Marie-Sklodowska Curie Fellowships.

March 28, 2017

7th CeMM S.M.A.R.T. Lecture with Hermann Hauser

In CeMM’s 7th S.M.A.R.T. Lecture, Hermann Hauser held a fascinating talk on how “Machine learning is changing everything” – from every day communication technologies to transportation habits to business strategies. 

“Machine learning is the most powerful tool that mankind developed so far” – with these words, Hermann Hauser, physicist and extremely successful serial entrepreneur at Cambridge, opened his Lecture on one of the fastest developing technologies of our times. In contrast to similar sounding but refuted predictions on artificial intelligence, Hermann Hauser emphasized, the progress of machine learning clearly shows the real impact that this tool soon will have and already has on everyone’s life. 

Speech recognition in mobile phones, face recognition programs or recommender systems of commercial platforms are just some recent examples for the capabilities of machine learning. A key feature of this technology responsible for its outstanding success: instead of following pre-programmed rules, the system learns from big data. Overruling the deterministic character of classic programming, machine learning is based on probabilities that allow to make guesses and decisions. As quality, size and availability of data is constantly increasing, machine learning will improve and pervade more and more areas of our life, Hermann Hauser is convinced. Moreover, it will change the way business is made and affect a broad range of industries. 

While this new technology will offer humanity a broad range of innovations and advantages, Hermann Hauser also pointed out the risks: “The genie is definitely out of the bottle – now we must figure out how to ensure that super intelligent machines embody human values” he emphasized. Furthermore, they pose a major challenge for society: intelligent machines might put more than 50 % of jobs be in danger. However, at the same time machine learning opens up unique business opportunities, especially in the service and health care sector with its dramatic increase in high-throughput and sensor technologies.

Having funded more than 20 technology companies, including outstanding success stories like Advanced RISC Machines (ARM) that licenses the architecture for the most widely used microchips for smart phones, Hermann Hauser is an expert in identifying and foreseeing future trends. With his S.M.A.R.T. lecture on machine learning, he gave us a thrilling overview of the latest developments and presented some eye-opening features of this revolutionary technology. Our warmest thanks to Herman Hauser for a wonderful and illuminating evening at CeMM! 

March 13, 2017

ERC’s 10th anniversary: EU-LIFE statement on the need for increased ERC budget

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EU-LIFE, the alliance of research centres in life sciences congratulates the European Research Council (ERC) on its 10th anniversary and wishes to acknowledge publicly the key role of this European Commission initiative in promoting excellent basic research.

In only a decade, the ERC has become a flagship for excellent scientific research in - and for - Europe which is key to innovation.  This is particularly relevant because even though- and mainly because of- its impact is initially unpredictable, basic research is the most certain way to major innovation for the benefit of the society.

The ERC has proven very successful in attracting top researchers to Europe and in increasing the competitiveness of Europe’s research on a global scale. The ERC allows the brightest scientists to perform excellent research that sooner or later will pave the way to disruptive innovation from all scientific fields. Coupled to professional technology transfer, basic research is of utmost importance to boost innovation. The ERC Proof of Concept Grants are indispensable for the translation of disruptive innovation from basic research results. 

Without ERC grants, research institutions would not be able to attract many of the best scientists in the world. However, Europe’s scientific potential is still not being fully realised due to lack of funding, many great research ideas fully fitting ERC evaluation criteria are put on hold, simply because of the current ERC budget limits. With an increased ERC budget excellent research will further flourish in Europe, making it even more attractive for top researchers. 

As such, we urge politicians from all Members States and the European Union institutions to unequivocally support the ERC namely by increasing its budget in the next framework programme the FP9 and clearly endorsing its guiding principles of scientific merit and independence.

March 07, 2017

Kickoff for Pharmacoscopy – a novel tool for precision medicine

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In light of the importance of research on precision, molecular, and personalized medicine, CeMM and the Medical University of Vienna hosted on March 6, 2017 a kick off meeting to celebrate the start of Pharmacoscopy, a novel high-content screening and imaging platform to break resistance of relapsed and refractory hematological malignancies - a true bench-to-bedside circle.

This meeting presented and celebrated the collaborative project between the Superti-Furga and Kubicek laboratories at CeMM and the Division of Hematology and Hemostaseology, Department of Internal Medicine I of the medical University of Vienna. The Pharmacoscopy platform is funded with the precision medicine grant from the WWTF (Wiener Wissenschafts-, Forschungs- und Technologiefonds / Vienna Science and Technology Fund) awarded to Giulio Superti-Furga and Ulrich Jäger.

The meeting began by reviewing the importance of the strong CeMM and MedUni Wien collaborative atmosphere that has propelled basic and translational science, as reiterated by the Vice Rector for Research and Innovation Michaela Fritz. Christoph Zelinski, Director of the Department of Internal Medicine I, touched upon ongoing precision medicine programs in the MedUni Wien such as the EXACT trial. Ulrich Jäger, Head of the Division of Hematology and Hemostaseology, further spoke about the need for personalized and precision medicine in the hematological space, where functional testing that will be used to meet the aims of the WWTF grant can synergize with genetic testing that is clinically routine.

CeMM scientific Director Giulio Superti-Furga and his Senior Postdoctoral Fellow Gregory Vladimer outlined the image-based screening platform that is the backbone of this program, and how the technology is currently being used for clinical utility. The meeting was finished by Ulrich Jäger presenting interim results of an ongoing clinical study aimed at describing the benefits of data generated through this collaboration for the treatment of patients.

The Pharmacoscopy project aims to break resistance of refractory blood cancers through ex vivo automated image-based analysis of drug action, and potentially drive clinical trials of already approved drugs in off-indication blood cancers. The approach provides a very concrete and actionable platform for precision medicine and the use of off-indication approved drugs for late stage hematological malignancies. The collaboration is tuned directly to unmet clinical needs of resistant blood cancer patients.

February 21, 2017

First breath shapes the lung’s immune system

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With the first breath, the lungs require to develop immunological defense mechanisms while maintaining the gas exchange. The postnatal immunological development of the lungs remained largely unknown until the group of Sylvia Knapp at CeMM and the Medical University of Vienna shed light at a complex immune program that starts right after birth: the study published in Cell Reports reveals how first breath-induced interleukin-33 signaling shapes the performance of pulmonary immune cells and influences anti-bacterial defenses.

(Vienna, February 21, 2017) The lung is an important interface between the body and the outside environment: with each breath, a surface of roughly 100 square meters exchanges oxygen for carbon dioxide. More than 10,000 liters of air pass adult lungs every day and with this come numerous viruses, bacteria and pollutants, which need to be prevented from entering the body.

To defend the organism from these intruders, the lungs harbor their own arsenal of highly specialized immune cells that are equipped to maintain the balance between host defense and tissue quiescence. However, how this balanced immune homeostasis in lungs emerged after birth, was largely unexplored. Now, for the first time, the group of Sylvia Knapp showed with the help of mouse models that the very first breath of a newborn releases crucial signals that shape the lifelong immunological milieu of lungs.

The study, published in Cell Reports (DOI:10.1016/j.celrep.2017.01.071), reveals that the mechanical forces of spontaneous ventilation at birth lead to the release of interleukin (IL)-33, a cytokine with a wide-range of effects: So-called “type 2 innate lymphoid cells” (ILC2s) follow the IL-33 signal and migrate into the lung tissue, where they release IL-13, another cytokine. This second signal determines the faith of alveolar macrophages by inducing the anti-inflammatory M2 phenotype.

The described mechanisms are crucial in achieving lung quiescence after the first contact with the outside world. However, these processes at the same time increase the susceptibility to bacterial infections, such as bacterial pneumonia - the primary cause of death by an infectious disease in Western countries.

Publication

Simona Saluzzo, Anna-Dorothea Gorki, Batika M. J. Rana, Rui Martins, Seth Scanlon, Philipp Starkl, Karin Lakovits, Anastasiya Hladik, Ana Korosec, Omar Sharif, Joanna M. Warszawska, Helen Jolin, Ildiko Mesteri, Andrew N. J. McKenzie und Sylvia Knapp. First-breath induced type-2 pathways shape the lung immune environment. Cell Reports, February 21, 2017. DOI:10.1016/j.celrep.2017.01.071

Funding:

This study was supported by the Austrian Science Funds (FWF, DK CCHD), the Vienna Science and Technology Fund (WWTF) and grants from the Medical Research Council and the Wellcome Trust.

February 10, 2017

Christoph Bock receives Overton Prize

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We congratulate CeMM PI Christoph Bock on being awarded the 2017 Overton Prize of the International Society of Computational Biology (ISCB). Each year, this prestigious award is given to one early to mid-career scientist from any country who is recognized as an emerging leader in computational biology and bioinformatics. 

Christoph Bock has been one of the first computational biologists who dedicated his career to understanding epigenetics and the human epigenome. During his PhD in the lab of Thomas Lengauer at the Max Planck Institute for Informatics (2004-2008), he developed pioneering methods and software for analyzing and interpreting DNA methylation data. As postdoc in the laboratory of Alexander Meissner at the Broad Institute (2009-2011), he conducted large-scale epigenome analyses of stem cells and contributed to the Roadmap Epigenomics project.

Since 2012, Christoph Bock has been a Principal Investigator at CeMM and a Visiting Professor at the Medical University of Vienna. His research on epigenetic biomarker development helped established the practical value of epigenetics for personalized medicine. He has also been one of the lead bioinformaticians in the BLUEPRINT epigenome project and the International Human Epigenome Consortium. Christoph Bock received an ERC Starting Grant in 2015 and a New Frontier Group award by the Austrian Academy of Sciences in 2013. 

In the light of these achievements, the ISCB’s announcement of the 2017 Overton Prize highlights Christoph Bock as “a rising star in epigenetic data analysis.”

The Overton Prize was instituted in 2001 to honor the untimely loss of G. Christian Overton, a leading bioinformatics researcher and a founding member of the ISCB Board of Directors. Over the last 16 years, the prize has been awarded to an outstanding group of computational biologists (https://www.iscb.org/iscb-awards/overton-prize). 

The ISCB is the world’s leading professional society for computational biology and bioinformatics. It seeks to communicate the significance of computational biology to the larger scientific community, to governmental organizations, and to the general public; the society serves its members locally, nationally, and internationally; it provides guidance for scientific policies, publications, meetings, and distributes information through multiple platforms.

February 02, 2017

CeMM statement on the importance of freedom of movement for the scientific discovery process

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(Modern) civil societies rely on the sharing of goods and information that allow the best use of resources and labor for the common good and well-being of the people. At the heart of all innovation in human civilization is the scientific research process. 

No Ideas – No Scientific Progress: Progress in all scientific disciplines, whether in the natural sciences, or humanities, mathematics, engineering or medicine, dramatically relies on the free circulation of ideas within a large and dynamic community of individuals and between the individuals and the cultural environment. Circulation and exchange of ideas, in turn, rely on the free exchange of people across nations. People move to visit schools and universities, to refine training in laboratories and institutions, to attend conferences, workshops, short visits, or sabbatical leaves. Avicenna (Ibn-Sīnā), Leonardo, Erasmus, Darwin, Marie Skłodowska Curie, Einstein are just famous examples of scientist that travelled intensively and made some of their most important contributions away from the environment they were born in. 

For all scholars and students, the ability to travel freely should be a fundamental right. CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, issues a plea to all politicians and policy makers in the world to do everything in their power to promote the freedom to travel and to enter countries. We express solidarity with all colleagues worldwide who currently suffer from travel restrictions and tell them that we are committed to engage society until these fundamental rights are (re-)installed. For the sake of knowledge, diversity, science and humankind.

CeMM is a supporter of the following EMBO initiative, offering temporary bench or desk space for US-based scientists who are stranded abroad:

January 31, 2017

Epigenetic diversity in childhood cancer

Researchers at the St. Anna Children’s Cancer Research Institute (CCRI) and CeMM observed unexpected variety in the epigenome of Ewing sarcoma, an aggressive childhood cancer. This finding, published in Nature Medicine, supports the importance of epigenetics in pediatric tumors and provides new perspectives for developing personalized therapies.

Tumors of the elderly, such as breast cancer and colon cancer, accumulate thousands of DNA mutations. These genetic defects contribute to cancer-specific properties including uncontrolled growth, invasion in neighboring tissues, and evasion from the immune system. Similar properties are also found in childhood cancers, although those tumors carry much fewer genetic defects, making it difficult to explain their clinical heterogeneity.

This is particularly true for Ewing sarcoma, an aggressive bone cancer in children and adolescents. A team of scientists by Eleni Tomazou from the St. Anna Children’s Cancer Research Institute in Vienna found that the disease’s clinical diversity is reflected by widespread epigenetic heterogeneity. Using novel bioinformatic methods developed by Nathan Sheffield at CeMM, the scientists studied the tumors’ DNA methylation patterns.

Ewing sarcoma showed unique characteristics that differ markedly from others cancers, and the DNA methylation patterns also varied between patients. Moreover, the researchers found that Ewing sarcoma tumors appear to retain part of the characteristic DNA methylation patterns of their cell-of-origin. Thus, the diverse clinical courses observed among Ewing sarcoma patients may be explained by the combination of Ewing sarcoma specific and cell-of-origin specific DNA methylation patterns. 

“From these new insights into the biology of Ewing sarcoma we expect new impulses for personalized therapy of this aggressive cancer”, Heinrich Kovar, Scientific Director of St. Anna Children’s Cancer Research Institute, optimistically states. “Our findings also provide an interesting concept for other cancer with low genetic complexity. In the era of precision medicine, understanding the causes and consequences of tumor heterogeneity will be crucial to treat in a targeted way”, Christoph Bock, Principal Investigator at CeMM, adds.

Publication:

Nathan C Sheffield, Gaelle Pierron, Johanna Klughammer, Paul Datlinger, Andreas Schönegger, Michael Schuster, Johanna Hadler, Didier Surdez, Delphine Guillemot, Eve Lapouble, Paul Freneaux, Jacqueline Champigneulle, Raymonde Bouvier, Diana Walder, Ingeborg M Ambros, Caroline Hutter, Eva Sorz, Ana T Amaral, Enrique de Álava, Katharina Schallmoser, Dirk Strunk, Beate Rinner, Bernadette Liegl-Atzwanger, Berthold Huppertz, Andreas Leithner, Gonzague de Pinieux, Philippe Terrier, Valérie Laurence, Jean Michon, Ruth Ladenstein, Wolfgang Holter, Reinhard Windhager, Uta Dirksen, Peter F Ambros, Olivier Delattre*, Heinrich Kovar*, Christoph Bock*, and Eleni M Tomazou* (*jointly directed this work). DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma. Nature Medicine, 30 January 2017. DOI:10.1038/nm.4273

Funding:

This work was partly funded by the Austrian National Bank (OeNB), a charitable donation from Kapsch Group (http://kapsch.net/kapschgroup), the Austrian Science Fund (FWF), the Human Frontier Science Program, and the Austrian Academy of Sciences.

January 30, 2017

LIBRA Workshop “Best Practice in Gender-Inclusive Recruitment Processes”

On January 26, 2017, a LIBRA Workshop on “Best Practice in Gender-Inclusive Recruitment Processes” with representatives of the partner institutes took place at CeMM in Vienna. It provided expert insights into the topic of unbiased recruitment with the goal to start discussions on best practices, and to define recommendations to remove gender barriers in hiring processes at the LIBRA partner institutes, especially for leading positions. 

LIBRA is an EC funded project which brings together ten research institutes in life sciences in ten European countries. They all are members of the alliance EU-LIFE, which aims to build and promote excellence in life sciences throughout Europe. Their commitment to excellence is also a commitment to diversity and gender equality. CeMM in collaboration with the Max-Delbrück Center for Molecular Medicine Berlin coordinates LIBRA's centralised activities to recruit without gender bias including the dissemination of gained knowledge. Additional topics within LIBRA focus on career development and training, work-life balance, and sex and gender dimensions of research. 

We are grateful to our guest speakers who shared their expertise with us on why diversity matters, how job advertisements can make a difference, and what to consider to make a fair assessment of candidates possible. 

Anna Beninger, Director, Research at Catalyst Inc., USA

Saher Ahmed, Athena SWAN Project Manager, Wellcome Trust Sanger Institute, UK

Eva Lübke, Project Manager at the Chair of Econometrics at the University of Mannheim, Germany

We would also like to thank Petra Unger for a very interesting guided tour “Female Traces” through the first district of Vienna the evening before the workshop started. It reminded us that history was made by both women and men alike, although it is hard to find memorials or texts in history books commemorating women. 

Reference:

Gaucher D et al. Evidence that gendered wording in job advertisements exists and sustains gender inequality, J Pers Soc Psychol., doi: 10.1037/a0022530

January 19, 2017

CRISPR meets single-cell sequencing in new screening method

A new cell screening method combines two revolutionary tools of biomedical research: Scientists at Christoph Bock’s lab have integrated CRISPR genome editing with single-cell RNA sequencing. Their study, published in Nature Methods, establishes a method for studying gene regulation in unprecedented scale and detail.

(Vienna, 19 January 2017) Genome editing using CRISPR/Cas9 “gene scissors” is a powerful tool for biological discovery and for identifying novel drug targets. In a new article published in Nature Methods (DOI: 10.1038/nmeth.4177), a team of CeMM scientists led by Christoph Bock now present a method that combines the strengths of pooled and arrayed CRISPR screens: By integrating CRISPR genome editing with single-cell RNA sequencing, they were able to determine the gene-regulatory impact of many genes in parallel, studying thousands of individual cells in a single experiment. 

Bock’s team succeeded with an elegant design that takes advantage of cutting-edge molecular technologies: The study’s first author Paul Datlinger created a viral vector for making the CRISPR guide-RNAs visible in single-cell sequencing experiments, and the latest droplet-based methods for single-cell RNA sequencing provided sufficient throughput to characterize the effect of thousands of genome editing events in individual cells.

Combining two of the most promising fields of genomics, the CROP-seq (for “CRISPR droplet sequencing”) method enables high-throughput analysis of gene regulation at a scale and detail that would be difficult to achieve with other methods. Furthermore, with falling single-cell sequencing costs, this technology could give rise to the first comprehensive maps of the regulatory effects for each of the 23,000 genes in the human genome.

“We will use CROP-seq to study the interplay of genetic and epigenetic factors in leukemia development”, says Christoph Bock, advancing the laboratory’s European Research Council (ERC) funded project on epigenome programming. “If we understand what it takes to make a cancer cell in the test tube, we can find new ways to interfere and revert cells to a less harmful state”.

CROP-seq was developed as an open source method. All data, protocols, reagents and software that are part of CROP-seq will be freely shared by CeMM, enabling other scientists to use and extend the method in their own work. The ambition to make new methods as widely available as possible is part of CeMM’s commitment to advancing biomedical research.

Publication:

Paul Datlinger, André F Rendeiro, Christian Schmidl, Thomas Krausgruber, Peter Traxler, Johanna Klughammer, Linda C Schuster, Amelie Kuchler, Donat Alpar and Christoph Bock. Pooled CRISPR screening with single-cell transcriptome readout. Nature Methods, 18 January 2017. DOI: 10.1038/nmeth.4177.

Funding: 

The study was partly funded by a New Frontiers Group award of the Austrian Academy of Sciences and by an ERC Starting Grant.