Researchers at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases in Vienna, the University Medical Center of Regensburg, and the National Institute of Hematology and Infectious Diseases and the Semmelweis University in Budapest have studied the response to targeted leukemia therapy in unprecedented detail, using single-cell sequencing and epigenetic analysis. The paper published in the journal Nature Communications uncovers a precise molecular program in patients with chronic lymphocytic leukemia (CLL) who start treatment with the targeted cancer drug ibrutinib. While this program was shared by all patients, the speed of its execution differed widely. These results will help develop personalized strategies for managing CLL as a chronic disease, which is particularly relevant for CLL as a disease of the elderly.
Chronic lymphocytic leukemia (CLL) is the most common form of blood cancer (leukemia) in the Western world, affecting approximately 1.2% of all cancer patients. This type of cancer starts with the lymphocytes (a type of white blood cells) that are produced in the bone marrow. CLL is characterized by the proliferation of abnormal lymphocytes (B cells) that fail to mature and grow out of control. These abnormal cells accumulate in the bone marrow and lymph nodes, taking the place of other healthy cell types and impeding their normal development. Finding the most suitable therapy for each patient poses a challenge due to the clinical and molecular heterogeneity of this disease, with some patients facing slow disease progression, whereas others face rapid progression and require quick medical response.
The cancer drug ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has remarkable efficacy in most patients with CLL. It is becoming the standard of care for most patients requiring treatment due to its clinical efficacy and mostly tolerable side effects. However, it does not cure the disease, and patients must undergo prolonged periods of treatment. Christoph Bock and his group at CeMM investigated the molecular program with which CLL cells and other immune cells response to ibrutinib treatment in patients with CLL. Their goal was to learn the epigenetic and transcriptional patterns that predict how swiftly the treatment is having an effect on the CLL cells and how long it takes for the disease to respond in each individual patient.
In previous studies, scientists had investigated only specific aspects of the molecular response to ibrutinib, focusing largely on genetic drug resistance or the transcriptome response of cancer cells. For the first time, CeMM researchers provide a comprehensive genome-scale, time-resolved analysis of the regulatory response to this drug in primary patient samples. The authors used a combination of immunophenotyping, single-cell transcriptome profiling (scRNA-seq) and chromatin mapping (ATAC-seq) to jointly monitor the activity, regulation and expression of the CLL cells and other cell types of the immune system. Importantly, they performed this analysis at eight pre-defined time points during the ibrutinib therapy, following seven individual patients over a standardized 240-day period after the start of the treatment.
Through integrative bioinformatic analysis of the resulting dataset, the authors were able to describe at high resolution how ibrutinib induces a very consistent chain of events on cancer cells over time across all patients. They found that ibrutinib first acts right at the center of the CLL cells’ activity, causing the genes that establish the cancer cell identity of the CLL cells to shut down, and then puts them in a dormant state. This means that the cancer cells stop dividing but quiescently survive, waiting for the right environment conditions to begin proliferation once again.
The present study by André Rendeiro, Thomas Krausgruber and colleagues is the result of cross-disciplinary collaborations with researchers from the Department of Hematology and Stem Cell Transplantation of the National Institute of Hematology and Infectious Diseases at the Central Hospital of Southern Pest, and the Department of Pathology and Experimental Cancer Research of the Semmelweis University in Budapest (Hungary). It constitutes one of the first high-resolution, multi-omics time series of the molecular response to targeted therapy in cancer patients, and it establishes a broadly applicable approach for analyzing drug-induced regulatory programs, identifying molecular response markers for targeted therapy. Finally, the study could help stratify patients into fast and slow responders based on characteristic molecular markers and open up new directions for the development of ibrutinib-based combination therapies for CLL.
The study “Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib response in chronic lymphocytic leukemia” was published in Nature Communications on 29 January 2020 DOI: 10.1038/s41467-019-14081-6
André F. Rendeiro*, Thomas Krausgruber*, Nikolaus Fortelny, Fangwen Zhao, Thomas Penz, Matthias Farlik, Linda C. Schuster, Amelie Nemc, Szabolcs Tasnády, Marienn Réti, Zoltán Mátrai, Donat Alpar+, Csaba Bödör+, Christian Schmidl+, Christoph Bock+ * shared first-authorships + shared co-last authorships
The study was funded with support of a New Frontiers Group award of the Austrian Academy of Sciences and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant Agreement No 679146, awarded to Christoph Bock). Thomas Krausgruber was supported by a Lise-Meitner fellowship from the Austrian Science Fund (FWF M2403). Nikolaus Fortelny was supported by a fellowship from the European Molecular Biology Organization (EMBO ALTF 241-2017). Donat Alpar and Csaba Bödör were supported by the K119950, KH17-126718, NVKP_16-1-2016-0004, and NVKP_16-1-2016-0005 grants of the Hungarian National Research, Development and Innovation Office, the Janos Bolyai research scholarship, and the LP95021 grant of the Hungarian Academy of Sciences. Christian Schmidl was supported by a Feodor Lynen Fellowship of the Alexander von Humboldt Foundation.
The next PhD Program of CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences in Vienna will start in September 2020. We are offering 15 fully funded PhD positions at CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, and LBI-RUD, the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases.
• Do you want to work in an environment that promotes free-minded scientific creativity, and translate your findings to impact medical practice and improve healthcare?
• Are you excited to gain a new understanding of the molecular physiology and pathology of humans?
• Do you want to join an international group of highly collaborative and successful colleagues that help you achieve your training and research goals?
• Are you a person who enjoys teamwork across disciplines and within a broader cultural and social context?
The research area
The 2020 CeMM PhD Program will focus on the thematic areas of Infection, Immunity, Metabolism, Cancer, Rare Diseases, Network Medicine, and Design Chemistry. These areas are built on the pillars of epigenetics and genome integrity, bioinformatics and systems biology, high-throughput genetics, genomics and proteomics, molecular and cell biology, chemical biology, and organic chemical synthesis.
Our goal is to enable and empower students with the ability to successfully design, execute, manage and explain a research project in modern molecular medicine, through a strongly participatory and interactive
program. The program is conceptualized in three “modes”: collect, connect and contribute.
These will guide you through scientific excellence in data generation and validation to responsible and professional scientific citizenship.
• An exceptionally motivated PhD candidate with a keen interest in interdisciplinary teamwork and science that nurtures the precise, personalized, preditive and preventive medicine of the future
• Excellent in writing and speaking English
• A candidate with (or will soon obtain) a final degree in medicine, biology, chemistry, bioinformatics, computer science, engineering, physics, mathematics or a similar subject (minimum requirement is a 4-year Bachelor's degree)
The host and partner institutes
CeMM and LBI-RUD are partner institutes with identical principles of excellence, competitiveness, internationality, as well as mentoring and training, together with the Medical University of Vienna, and the Children’s Cancer Research Institute (CCRI) of the St. Anna Children’s Hospital they operate in a unique mode of super-cooperation. Here biology is connected with medicine, experiments with computation, discovery with translation, and science with society and the arts.
The mission of CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences is to achieve maximum scientific innovation in molecular medicine to improve healthcare. At CeMM, an international
and creative team of scientists and medical doctors pursues free-minded, basic life science research in a large and vibrant hospital environment of outstanding medical tradition and practice. CeMM’s research is based
on post-genomic technologies and focuses on societally important diseases, such as immune disorders and infections, cancer and metabolic disorders. The goal of CeMM is to pioneer the science that nurtures the precise, personalized, predictive and preventive medicine of the future. CeMM is part of EU-LIFE an alliance of 13 top research centres in life sciences to support and strengthen European research excellence.
LBI-RUD, the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases focuses its research on rare diseases of the immune system, hematopoiesis, and the nervous system. This research will not only provide the basis for targeted therapies, but also provide unique and novel insights into human biology far beyond the specific disease. LBI-RUD is highly connected in global networks promoting cooperation and synergy between different disciplines and engaging rare disease patients.
CeMM and LBI-RUD enjoy a privileged location right in the centre of the Medical Campus Vienna, one of the largest in Europe, door-to-door with the Medical University of Vienna and the Vienna General Hospital (AKH). The Medical University of Vienna is the largest medical research institution in Austria and the AKH is one of the largest hospitals in Europe treating several hundred thousand people a year. Close by, the Children’s Cancer Research Institute (CCRI) of the St. Anna Children’s Hospital work hard to develop new and improved treatment options for the 250-300 children and adolescents diagnosed with cancer each year in Austria.
The partner institutions, CeMM, LBI-RUD, CCRI and the Medical University of Vienna are located within walking distance of Vienna’s historical city centre. Vienna is repeatedly ranked as the world’s best city to live in and is a United Nations city with a large international, English- speaking community. The official language at CeMM is English, and more than 40 different nationalities are currently represented at the institutes.
For more information and application details please have a look at: CeMM PhD Program Open Call 2020 (PDF)
Deadline for applications: 31 January 2020
From 15 to 17 January 2020, the Christian Doppler Laboratory Closing Symposium “From Understanding Chromatin Dynamics to Therapeutics Targeting” will take place at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in Vienna (Austria). The event is jointly organized by CeMM PI Stefan Kubicek, CeMM PostDoc Sandra Schick, and Senior Principle Scientist Simon Wöhrle (Boehringer Ingelheim). The highlight of the programme is the keynote lecture by Brian R. Cairns, Chair of the Oncological Sciences Department at the University of Utah School of Medicine, and an investigator with the Huntsman Cancer Institute (USA). The line-up of speakers also includes EMBO Members Tom Owen-Hughes (University of Dundee, UK) and Dirk Schübeler (FMI for Biomedical Research in Basel, Switzerland), among other excellent speakers from Austria, Germany, Switzerland, the United Kingdom and the United States.
The symposium is organized on the occasion of the ending of the Christian Doppler Laboratory for Chemical Epigenetics and Antiinfectives, a close collaboration between Stefan Kubicek's Group at CeMM, Boehringer Ingelheim and Haplogen, to celebrate its successful outcome. The Christian Doppler Research Association promotes the cooperation between science and business. Under the direction of highly qualified scientists, research groups work in close contact with the commercial partners on innovative responses to business-related research questions.
For the past seven years, Stefan Kubicek’s Group has collaborated with industry on application-oriented basic research, which has resulted in 17 high-impact publications including the CD Lab as an affiliation, nine of them with Stefan Kubicek as a corresponding author. The key highlight was the study published last year in Nature Genetics with Sandra Schick as first author (“Systematic characterization of BAF mutations explains intra-complex synthetic lethalities in human cancers”. DOI: 10.1038/s41588-019-0477-9).
The CD Laboratory programme has funded a compact research group of 13 scientists over the past seven years, who have worked at CeMM, and are all still active in research. Some of them have moved to independent academic positions and others have also taken on leadership roles in industry. The CD Laboratory funding programme has supported the research of Stefan Kubicek’s Lab, resulting in an ERC Consolidator Grant “CHROMABOLISM” awarded in 2018, and has also laid the foundation for future research. We thank the Christian Doppler Research Association, Boehringer Ingelheim and Haplogen for this successful collaboration.
At the end of this year, Giulio Superti-Furga, Scientific Director of CeMM and Professor for Medical Systems Biology of the Medical University of Vienna, will terminate his appointment as Member of the Scientific Council of the European Research Council, which he started in January 2017. We thank Giulio for this important scientific community service during difficult political times, strongly advocating for the support of frontier research on new ideas, as the best means to reach innovation and economic welfare, and to sustain the ground for democracy. Having been awarded two ERC Advanced Investigator Grants in the past 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, will continue to be a strong supporter of the ERC, which celebrated its 10th anniversary in 2017 and is now preparing for Horizon Europe.
Coinciding with this is the end of the function of ERC President Jean-Pierre Bourguignon, a renowned French mathematician, who has been highly successful at further increasing the prestige of the ERC and effectively safeguarding the budget. CeMM’s students, postdocs and faculty have a fond memory of his visit in Vienna in October 2017. As part of the scientific community, we thank Jean-Pierre Bourguignon for his inspiring leadership. From 2010 to 2013 Prof. Helga Nowotny, a Viennese Professor of Social Studies of Science, also held this prestigious position. We look forward to the term of the designated new President Mauro Ferrari, who will start in January 2020. We wish him success at leading the ERC in the future 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. With its different programme,s it has created a very positive impact on the attractiveness of Europe as a research area.
Researchers at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences identified a key mechanism for how antiviral immune responses reprogram liver metabolism. Their recent study, which was published in the renowned scientific journal Immunity, investigated the communication between inflammation and liver metabolism during chronic viral infection. Surprisingly, the antiviral cytokine type I interferon (IFN-I) was found to be a master regulator of metabolic pathways in liver cells. The researchers focused on the urea cycle, a central metabolic node, and found that it is disrupted by IFN-I during viral infection. This led to altered serum metabolite concentrations which regulated antiviral immunity and reduced liver pathology.
The liver is a crucial organ for systemic metabolism in our body. Apart from the turnover of biomolecules and drug metabolism, the liver’s main function is the removal of toxic substances from the organism. Hepatocytes, or liver cells, are the most abundant cell type and functional unit of the liver. They are metabolic powerhouses in the healthy organism, but they also serve as important immune signaling platforms during infections. As such, they have the potential to react to a range of cytokines – small molecules that are essential for the coordination of immune responses.
Previous studies in the field of immunology and metabolism, or immunometabolism, unveiled groundbreaking mechanisms about how cells of the immune system need to adjust their metabolism to perform their functions to fight pathogens and cancer. Building on this, Andreas Bergthaler and his group at CeMM aimed to study the immunometabolic changes that occur in the whole organism during infection. They particularly focused on the liver due to its important role in controlling systemic metabolism.
To dissect the involved complex processes, the authors took advantage of the benchmark model of chronic infection, the lymphocytic choriomeningitis virus (LCMV). Research with LCMV had already led to fundamental insights into immunology over the past 80 years, and notably contributed to three Nobel Prizes. Among them is the 2018 Nobel Prize in Physiology or Medicine, which was awarded to James Allison and Tasuku Honjo for their discoveries relating to the revolutionary new cancer immunotherapies which exploit the body’s own immune killer cells, or CD8 T cells.
The present study by Alexander Lercher, Anannya Bhattacharya et al. is the result of cross-disciplinary collaborations with researchers from the Medical University of Vienna and the University of Veterinary Medicine in Vienna (Austria), as well as from the Hannover Medical School (Germany), the Cantonal Hospital St. Gallen (Switzerland) and the company Bio-Cancer Treatment International Ltd (China). The study was designed as an integrative unbiased approach to investigate the molecular changes in the liver during chronic infection. Next to expected inflammatory changes, the authors identified intriguing changes in hepatocyte metabolism. Many central metabolic pathways, among them the urea cycle, were found to be repressed upon infection. The urea cycle is essential to remove toxic ammonia from the body to prevent brain damage. Surprisingly, the researchers identified the antiviral cytokine signaling pathway of type I interferons (IFN-I) as a regulator of the urea cycle. This resulted in altered blood concentrations of the amino acids arginine and ornithine. “A key experiment for us was that when we removed the receptor for IFN-I on the surface of hepatocytes, we didn’t see these metabolic changes anymore”, says Alexander Lercher, first author of the study and PhD student in the laboratory of CeMM Principal Investigator Andreas Bergthaler. The systemic changes of arginine and ornithine were found to inhibit antiviral CD8 T cell responses and to reduce liver damage.
One of the most important revelations of this study was the identification of IFN-I signaling as a master regulator for the repression of metabolic processes in hepatocytes upon infection. “We were really surprised that an antiviral molecule affects such vital biological processes as the urea cycle during infection”, says Michael Trauner, co-author of the study and head of the Department of Gastroenterology and Hepatology at the Medical University of Vienna. Together, these findings shed new light on how the body’s immune system evolved to regulate liver metabolism that modulate CD8 T cell responses and reduce collateral tissue damage during infection. Andreas Bergthaler: “We regard this study an important contribution to the field of systemic immunometabolism. It also highlights the central role of the liver for our immune system and how organs of the body communicate through metabolites.” In the future, such findings may be exploited to therapeutically intervene with the regulation of metabolic processes to modulate CD8 T cell responses in diverse diseases such as infection, cancer and autoimmunity.
The study “Type I interferon signaling disrupts the hepatic urea cycle and alters systemic metabolism to suppress T cell function” was published in Immunity on 26 November 2019.
Alexander Lercher*, Anannya Bhattacharya*, Alexandra M. Popa, Michael Caldera, Moritz F. Schlapansky, Hatoon Baazim, Benedikt Agerer, Bettina Gürtl, Lindsay Kosack, Peter Májek, Julia S. Brunner, Dijana Vitko, Theresa Pinter, Jakob-Wendelin Genger, Anna Orlova, Natalia Pikor, Daniela Reil, Maria Ozsvár-Kozma, Ulrich Kalinke, Burkhard Ludewig, Richard Moriggl, Keiryn L. Bennett, Jörg Menche, Paul N. Cheng, Gernot Schabbauer, Michael Trauner, Kristaps Klavins, Andreas Bergthaler
* shared first-authorships
The study was funded with support of the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant Agreement No 677006, “CMIL” to Andreas Bergthaler). Alexander Lercher, Anannya Bhattacharya and Julia S. Brunner were supported by a DOC fellowship of the Austrian Academy of Sciences. Natalia Pikor was supported by an Ambizione grant awarded by the Swiss National Science Foundation (PZ00P3_180011/1).
CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, announces the start of a three-year research collaboration with Pfizer Inc. to explore a combination of technologies aimed at expanding the druggable proteome. CeMM Principal Investigators Georg Winter (project coordinator), Giulio Superti-Furga and Stefan Kubicek, in collaboration with researchers from Pfizer’s Medicine Design organization based in Cambridge, USA, will aim to explore a discovery strategy that combines parallel, efficient ligand identification with focused degradation of individual targets.
Chemical proteomics approaches have traditionally been pursued at CeMM in the laboratories of Giulio Superti-Furga and Stefan Kubicek and led to a series of high-impact publications over the last decade. Project coordinator Georg Winter joined CeMM after postdoctoral research with Jay Bradner at the Dana Farber Cancer Center in Boston focusing in the field of Protein Degradation. Therefore, significant know-how, experimental and analytical pipelines are available at CeMM, including a proteomics facility with state of the art instrumentation and trained personnel. In close collaboration with the Pfizer team that brings a strong background in medicinal chemistry and chemical biology, the main aim of this partnership is to scout new corners of the “ligandable” proteome followed by pharmacologic control over selected cellular proteins, including some hitherto deemed as poorly druggable.
“Through this collaboration with CeMM, we have the potential to further build our capabilities in chemical biology and medicinal chemistry and open up areas of target space that have historically been challenging,” said Charlotte Allerton, Senior Vice President and Head of Medicine Design, Pfizer.
“This collaboration will allow us to apply some of the most powerful contemporary technologies in chemical biology at a scale beyond most academic research. Together with Pfizer, we hope to inspire future drug discovery efforts,” said Georg Winter, CeMM Principal Investigator and project coordinator.
The mission of CeMM, the Research Center for Molecular Medicine of the Austrian Academy is to achieve maximum scientific innovation in molecular medicine to improve healthcare. At CeMM, an international and creative team of scientists and medical doctors pursues free-minded basic life science research in a large and vibrant hospital environment of outstanding medical tradition and practice. CeMM’s research is based on post-genomic technologies and focuses on societally important diseases, such as immune disorders and infections, cancer and metabolic disorders. CeMM operates in a unique mode of super-cooperation, connecting biology with medicine, experiments with computation, discovery with translation, and science with society and the arts. The goal of CeMM is to pioneer the science that nurtures the precise, personalized, predictive and preventive medicine of the future. CeMM trains a modern blend of biomedical scientists and is located at the campus of the General Hospital and the Medical University of Vienna.
Researchers at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences have developed a new methodology characterizing more precisely how drugs influence each other when combined during treatment. Their analysis of over 30k drug pairs applied to cell lines identified 1,832 interactions between 242 different drugs and sheds new light on how drugs perturb the underlying molecular networks. The findings have now been published in the scientific journal Nature Communications.
Combining two or more drugs can be an effective treatment of diverse diseases, such as cancer. Yet, at the same time, the wrong drug combination can cause major side effects. Currently there is no systematic understanding of how different drugs influence each other. Thus, elucidating how two given drugs interact, and whether they have a beneficial effect, would mean a major step towards drug development to treat diseases more effectively in the future.
On a molecular level, drugs cause complex perturbations of various cellular processes in our body. These processes are orchestrated by an intricate network of molecular interactions, the so-called interactome. Over the last decade, numerous studies have revealed a close relationship between the structure of the interactome and the functional organization of the molecular machinery within the cell. This opened exciting opportunities for using network-based approaches to investigate the foundations of both healthy and disease states. Following this trend, Principal Investigator Jörg Menche and his group at CeMM developed a novel mathematical framework for mapping out precisely how different perturbations of the interactome influence each other.
The new study performed by Caldera et al., represents the first general approach to quantifying with precision how drugs interact with each other, based on a mathematical model that considers their high-dimensional effects. Their research reveals that the position of targets of a given drug on the interactome is not random but rather localized within so-called drug modules. They found that the location of a drug module is linked to the specific cell morphological changes induced by the respective treatments, making morphology screens a valuable resource for the investigation of drug interactions. Further they identified various factors that contribute to the emergence of such interactions. Most notably, the distance between two drug modules on the interactome plays a key role: Certain types of interactions are more likely depending on the exact proximity between the two respective drug modules. If the modules are too far away from each other, it is rather unlikely that an interaction will take place.
“We developed a completely new methodology to classify drug interactions. Previous methods could characterize interactions only as synergistic or antagonistic. Our methodology is able to distinguish 12 distinct interactions types and also reveals the direction of an interaction”, says Michael Caldera, first author of the study and PhD student at Jörg Menche’s Group.
The study of the Menche group has broadened the understanding of how drugs perturb the human interactome, and what causes drugs to interact. Moreover, the introduced methodology offers the first comprehensive and complete description of any potential outcome that may arise from combining two perturbations. Finally, this methodology could also be applied to address other key challenges, such as dissecting the combined impact of genetic variations or predicting the effect of a drug on a particular disease phenotype. Their research forms a solid base for understanding and developing more effective drug therapies in the future.
The study “Mapping the perturbome network of cellular perturbations” was published in Nature Communications on 13 November 2019. DOI: 10.1038/s41467-019-13058-9
Michael Caldera, Felix Müller, Isabel Kaltenbrunner, Marco P. Licciardello, Charles-Hugues Lardeau, Stefan Kubicek and Jörg Menche
This work was supported by the Vienna Science and Technology Fund (WWTF) through project number VRG15-005.
On 6-8 November 2019, the 3rd RESOLUTE Consortium Meeting took place near Milan, Italy, and was hosted by Axxam within OpenZone. RESOLUTE is a public-private partnership, funded with a grant from the Innovative Medicines Initiative (IMI) and coordinated by CeMM and Pfizer, with 13 partners from academia and industry.
The first day of the meeting kicked off with updates from several RESOLUTE partners, which showcased the progress achieved since the last consortium meeting in Krems, Austria, in June 2019.
The second day was dedicated to a “Data Integration workshop”, where participants discussed insights and tools to extract knowledge from the combination of diverse data types generated within the RESOLUTE project. The workshop included keynote talks by Avner Schlessinger (Mount Sinai, New York, USA), Rob Russell and Francesco Raimondi (BioQuant Heidelberg, Germany), and Patrick Aloy (IRB, Barcelona, Spain). EFPIA representatives Andreas Steffen (Bayer AG), Robert Stanton (Pfizer Ltd), and Karsten Quast (Boehringer Ingelheim), as well as CeMM members Enrico Girardi and Eva Meixner, shared specific examples and tools related to data integration.
On the last day, RESOLUTE external collaborators presented several strategies to develop high-affinity binders for Solute Carriers (SLCs), which will help boost research on this protein class. This was followed by project-specific discussions leading to the definition of current priorities and plans for the upcoming year of RESOLUTE.
We would like to thank OpenZone and Axxam for the smooth organisation, and all participants and partner institutions for their enthusiasm and fruitful discussions!
Find out more about RESOLUTE: https://re-solute.eu
Congratulations to Thomas Reiberger, Associate Professor at the Division of Gastroenterology and Hepatology at the Medical University of Vienna, and Adjunct Principal Investigator at LBI-RUD and CeMM, for receiving the United European Gastroenterology Rising Star Award at the 2019 UEG Week in Barcelona!
Follow the Rising Star Talk of Thomas via live stream on 21 October 2019 at 4.20 pm: "Understanding pathophysiology in order to identify novel therapeutic strategies for chronic liver diseases”
Every year the National Societies Committee and the UEG Scientific Committee jointly select 6-8 emerging clinical scientists as Rising Stars. These are promising candidates under the age of 40 with an excellent scientific track record and internationally recognized and independent research.
The United European Gastroenterology (UEG), represents more than 30,000 medical specialists from every field in gastroenterology. The UEG Week attracts around 14,000 conference participants each year.
Thomas Reiberger, born 1982, joined the LBI-RUD and CeMM in 2018 as an Adjunct PI. After obtaining his MD at the Medical University of Vienna, he did a first postdoc at the Department of Pathophysiology at the Medical University of Vienna, where he performed his first studies in the field of Liver Cell Biology. During his residency for Internal Medicine at the Divison of Gastroenterology and Hepatology at the Medical University of Vienna, Thomas Reiberger followed the career of a physician scientist and focused his translational studies on portal hypertension and fibrosis in patients with viral hepatitis. Next to the clinic he established the Vienna Hepatic Experimental (HEPEX) Laboratory at the Medical University of Vienna. In 2011 he received his Venia docendi and 2012 he obtained his board certification for Internal Medicine. After another postdoctoral fellowship in the United States from 2012 to 2015, Thomas Reiberger was appointed as Associate Professor of Gastroenterology and Hepatology at the Medical University of Vienna.
More information: https://www.meduniwien.ac.at/web/ueber-uns/news/
Joanna Loizou, Principal Investigator at CeMM, together with Jacob Corn, Eidgenoessische Hochschule Zuerich (ETHZ), Switzerland and Steve P. Jackson, The Gurdon Institute, University of Cambridge, UK, are awarded ERC Synergy Grant for DNA-damage response systems. The prestigious funding worth round €8.86M for a period of six years, of which € 2.95M will go to Joanna Loizou´s group, will help provide major insights into human genome surveillance and speed the development of new therapies for cancer and other diseases.
ERC Synergy Grants are intended to enable a minimum of two and a maximum of four Principal Investigators and their teams to bring together complementary skills, knowledge, and resources in new ways that are more than additive, in order to jointly address ambitious research problems. In their project “Dna Damage Response: Actionabilities, Maps and Mechanisms” (Acronym: DDREAMM) Joanna Loizou, Jacob Corn and Steve P. Jackson team up to shed light on DNA-damage response (DDR) systems.
Within this ERC Synergy Grant, starting in January 2020, the three teams will devote the next six years to mapping and understanding how eukaryotic cells monitor and protect their genomes. To do this they will use cutting-edge technologies in gene editing and chemical biology. Hence, they will take multidisciplinary approaches to create deeply integrated genetic and physical maps of DNA repair pathways and interactions in many human cell types. This work will provide major insights into human genome surveillance in multiple cell types, yield powerful tools to precisely control DNA repair outcomes, and speed the development of new therapies for cancer and other diseases. In response to receiving this grant, Joanna says: ‘the ERC Synergy Grant allows Jacob, Steve and myself to bring together our unique expertise in an unparalleled manner, to tackle the fundamentally important question of how our genomes are maintained’.
In the research project, each individual lab will play to its strengths while also assimilating expertise from the other labs. As the ERC Synergy grant will be focused on rapidly evolving scientific arenas, the international partnership offers a possibility to collectively embrace and exploit the very latest technological developments and scientific opportunities, in ways that would not be possible if the three groups operated individually.
Joanna Loizou’s long-standing expertise is embedded in investigating the cellular pathways that respond to DNA damage, to maintain genome stability and suppress disease. Her important contributions within this field began during her PhD (2000-2004, UK) and continued during two postdoctoral positions (2004-2007, France and 2007-2011, UK). During these training posts, Joanna consistently made seminal discoveries, by identifying a novel kinase that regulates DNA repair (Loizou et al, Cell 2004), linking the DNA damage response to post-translational modifications and epigenetic regulation (Murr* & Loizou*, et al Nature Cell Biology 2006) and identifying and characterizing a novel tumour suppressor (Loizou et al, Cancer Cell 2011).
In September 2011, Joanna established her independent group at CeMM, Vienna, Austria. Her vision is to piece together the intricate puzzle that encompasses the human DNA damage response at the cellular level, hence providing a complete understanding of how such pathways go wrong in disease states, with a strong emphasis on cancer. To achieve this her team uses genome-scale approaches, based around genetics, genomics, proteomics and chemical biology. She hypothesizes, and have proven, that by investigating the regulatory pathways of DNA repair taking unbiased approaches, we can advance our knowledge of how cells respond to DNA damage, uncover genetic interactions required for DNA repair and cellular survival and unravel the impact on the genome upon engagement of DNA damage and DNA repair pathways. Hence, she envisages that her research will shed light on the mechanisms leading to cancer development and pave the way for better treatments for cancer and other DNA repair-associated diseases.