April 24, 2017

Next-Generation Microscopy with Pharmacoscopy

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 07, 2017

Kickoff for Pharmacoscopy – a novel tool for precision medicine

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.

January 16, 2017

Giulio Superti-Furga new Member of Scientific Council of the European Research Council (ERC)

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."

March 18, 2016

2nd ERC Advanced Investigator Grant

Giulio Superti-Furga, scientific director at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and Professor of Medical Systems Biology at the Medical University of Vienna is to receive the Advanced Investigator Grant of the European Research Council ERC in the amount of approximately 2.5 million euro. The term for the prestigious grant is 5 years.

"ERC Grants are the most important promotions for life sciences in Europe. Unfortunately, the situation is becoming increasingly competitive due to budget cuts," says Giulio Superti-Furga who has built up and is leading CeMM at the campus of the Medical University of Vienna and the Vienna General Hospital: "I am all the more delighted to receive this extraordinary distinction as it also confirms the relevance and quality of CeMM research." The goal of CeMM is to prepare the precise medicine of the future by decoding molecular causes for important diseases such as cancer, inflammation and immune disorders. Giulio Superti-Furga already received an ERC Advanced Grant in 2009 for the exploration of basic immune system mechanisms. In 2011, he also received the first ERC Proof of Concept Grant in Austria.

The molecular system biologist has been granted the present ERC funding for research into existing components in cell membranes that transport dissolved substances into cells. Previous studies have shown that these "cell gates", so-called SoLute Carrier Proteins (SLCs) perform an important task in regulating the cellular metabolism and are responsible for accepting medications. The goal of the research project with the title "Game of Gates" is to decode the previously unknown rules according to which cells open or close their gates, either permitting or preventing the entry of substances. Giulio Superti-Furga: "Thus far, SLCs were treated more or less as second-rate by the scientific community. However, we expect that insights from our study will significantly contribute to a new, fundamental understanding of cellular physiology and thus prepare the way for the development of new, targeted therapies for various illnesses." 

The ERC Advanced Investigator Grant is being awarded to Giulio Superti-Furga after two ERC Starting Grants had been given to Andreas Bergthaler and Christoph Bock in the autumn of 2015. Moreover, CeMM Principal Investigator Kaan Boztug won the bid – also in the autumn of 2015 – for founding the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases. The "Vienna Research Groups for Young Investigators" grant of the Vienna Science and Technology Fund WWTF had also been awarded to the CeMM PI Jörg Menche. All of these promotions once again emphasize the excellent work being performed at the CeMM.

September 21, 2015

A “hot” approach for understanding drug action and identifying new drug targets

How do successful drugs actually work? And how can we identify new targets for drug discovery to enable the development of novel potential therapeutics? A key challenge for scientists in academia and the pharmaceutical industry is to find out how small molecules such as drugs or cellular metabolites act within a cell – who are the mediators and effectors required for a drug or metabolite to exert their effect e.g. on cell proliferation, shape etc.? Based on the simple fact that interaction between a small molecule - such as a drug - and a given target protein increases the thermal stability of that protein, scientists at CeMM have developed a new state-of-art approach to reveal the cellular proteins that are engaged by small molecules and metabolites. By refining the established cellular thermal shift assay (CETSA) approach in which cells are treated with a small molecule and then heated to measure the differential protein stability upon target engagement and combining it with modern protein mass spectrometry a broad view of small molecule-protein interactions is provided. A particular advantage of the new methodology is the fact that the assay works with intact living cells and thus reflects a more natural (“physiological”) context in which the small molecule and its target proteins interact without any interference considering compound uptake, efflux, metabolism as well as cellular compartments. A potential future application includes the use of patient material to identify patient specific bio markers to enable personalized medicine.

Publication:
Kilian V M Huber, Karin M Olek, André C Müller, Chris Soon Heng Tan, Keiryn L Bennett, Jacques Colinge, Giulio Superti-Furga. Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling. Nature Methods, doi:10.1038/nmeth.3590.

Funding:
CeMM gratefully acknowledges funding from the Austrian Academy of Sciences, the European Union (FP7 259348, ASSET) and from the Austrian Science Fund (FWF F4711, MPN).