Adjunct Principal Investigator Positions at LBI-RUD and CeMM, Vienna
Starting or consolidated level to begin in 2018/2019
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 have identical principles of excellence, competitiveness, internationality as well as mentoring and training, and both operate in a unique mode of super-cooperation, connecting biology with medicine, experiments with computation, discovery with translation, and science with society. We are partner institutes and located in the very same research building in the middle of the Vienna medical campus. Both have a partnership with the Medical University of Vienna and several faculty members have dual affiliations.
To complement and strengthen the current Faculty, CeMM and LBI-RUD are offering Adjunct Principal Investigator positions to highly professional individuals who work on an exciting problem of molecular medicine, preferably but not exclusively pertaining to Rare and Undiagnosed Diseases, Molecular Pharmacology, Immunity, Infection Biology, Inflammation, Neurologic Diseases, Hematopoiesis, Hematological Malignancies, Genome Integrity, Blood, Vascular Disorders or Metabolic Disorders.
Whom we are looking for:
We are looking for MD and/or PhD scientists either at their first independent appointment or already at the consolidation stage to apply their expertise close to a clinical setting in a stimulating research environment. Required are scientific quality and originality, a track record of achievements as well as a collaborative and interdisciplinary mindset.
What we offer:
We offer a collaboration/affiliation contract for initially 5 years including a PhD student position, and some consumables and facility service funds. The unique opportunity to become part of the CeMM/LBI-RUD Faculty. Benefit from lively scientific exchange, extend your network, collaborate and explore new possibilities – in science and beyond.
If you have the necessary drive and passion to make a difference, apply now for one of several positions of ADJUNCT PRINCIPAL INVESTIGATORS at LBI-RUD/CeMM.
EU-LIFE, the alliance of 13 leading life science research institutes in Europe announced its reaction to the European Commission´s proposal for Horizon Europe, the next Framework Programme for Research and Innovation (FP9) that will run from 2021 to 2027.
The key points are as follows:
• EU-LIFE urges the European Parliament and the EU Council to push for a stronger Horizon Europe by raising its budget as recommended by several reports
• EU-LIFE encourages Horizon Europe to expand the extremely successful programmes it has initiated, namely the ERC grant system and Marie Skłodowska-Curie Actions, in addition to collaborative projects that address technological and environmental challenges facing our society today. These actions attract and foster the best and brightest minds, and encourage ground-breaking research that will ensure Europe’s leadership in technological and biomedical innovation in the future.
• EU-LIFE supports the statement released by 14 university organisations on calling for: increased total budget of Horizon Europe, a review of budget allocation, centre the Programme’s pillars on the realisation of the European Research Area, better integration among research, innovation and education.
• Support for the announced ‘mission’ actions and a recommendation that researchers and innovators are involved in identifying and managing missions
Immune cells promoting inflammation play a crucial role in the development of atherosclerosis. Scientists at CeMM and the Medical University of Vienna in collaboration with the University of Cambridge showed that a survival factor for those cells has also anti-inflammatory functions and a protective role in atherosclerosis. The study, published in Circulation, provides valuable new insight for atherosclerosis research and suggests a hitherto unknown, inherited risk factor for atherosclerosis.
Atherosclerosis, the pathological narrowing of blood vessels, is the underlying cause for the majority of strokes and heart attacks, the major causes of mortality worldwide according to the WHO. For the development of atherosclerosis, a special type of white blood cells called B2 lymphocytes have been suggested to play a crucial role. For their survival, they need the molecule BAFF. It has been shown, that deletion or blockade of the BAFF receptors at the surface of B2 lymphocytes reduces the development of atherosclerosis in mice. Hence, a similar effect was expected when BAFF is directly targeted.
With highly specific antibodies, BAFF can be bound and neutralized. Those antibodies where tested for their effects on the development of atherosclerosis in mice by scientists from CeMM and the Medical University of Vienna in collaboration with the University of Cambridge. The results were surprising: instead of reducing atherosclerotic lesion formation in the arteries of the tested mice, the antibody treatment lead to an increased plaque size. The findings were published in Circulation (DOI: 10.1161/CIRCULATIONAHA.117.032790).
The researchers - with Christoph Binder, CeMM PI and Professor for Atherosclerosis Research at the Medical University of Vienna as senior author - found BAFF to have anti-inflammatory properties, which has a positive effect on plaque size and atherosclerosis risk. The newly discovered mechanism is triggered by an alternative BAFF receptor (TACI) on the surface of macrophages, another type of immune cells. It was shown that these cells induce an anti-inflammatory process. This finding may provide important implications for atherosclerosis research and prevention: For example, mutations in the gene for TACI may confer an increased cardiovascular risk.
Dimitrios Tsiantoulas#, Andrew P. Sage#, Laura Göderle, Maria Ozsvar-Kozma, Deirdre Murphy, Florentina Porsch, Gerard Pasterkamp, Jörg Menche, Pascal Schneider, Ziad Mallat# and Christoph J. Binder#. (# equal contribution). BAFF Neutralization Aggravates Atherosclerosis. Circulation, June 5, 2018 . DOI: 10.1161/CIRCULATIONAHA.117.032790
The study was funded by the Austrian Science Fund FWF, the European Union, the British Heart Foundation and the European Research Council (ERC)
Fanconi anemia (FA), a rare, inherited disease, is caused by defective genes for DNA-repair in the cells of the patient leading to bone marrow failure, developmental abnormalities and increased cancer risk. Using genome-wide genetic approaches, researchers at CeMM systematically screened for the loss of an additional gene that could rescue the disease – and found it. The corresponding protein turned out to be a potential target that could be therapeutically exploited for FA. The study was published in Nature Communications.
Damaged DNA and its complex repair mechanisms is the research focus of the group of Joanna Loizou, Principal Investigator at CeMM, and finding new molecular targets to fight FA is one of their goals. In their latest study, published in Nature Communications (DOI 10.1038/s41467-018-04649-z), the researchers aimed to find additional genes that genetically interact with the diseased FA genes and are essential for the manifestation of the disease, and thereby, if destroyed, restore the ability of the cell to repair DNA crosslinks. The research project was performed in collaboration with scientists from the University of Cambridge, from the Leiden University Medical Center, the University of California, the University of Toronto and the group of Jörg Menche at CeMM.
The scientists, with former post doc of Loizou´s lab Georgia Velimezi and CeMM PhD student Lydia Garcia-Robinson as shared first authors, deployed a novel genetic screen to search for synthetic viable interactions, using a genome-wide loss-of-function approach that uses insertional mutagenesis achieved via a gene-trap approach, on special lines of FA-defective cells that only possess one copy of each gene. With this method, they scored a bulls eye: the researchers found an enzyme that removes ubiquitin, an important regulator of protein activity and half live, to be synthetic viable for FA gene deficiencies.
When the enzyme, called USP48, was artificially destroyed by CRISPR/Cas9, the FA-deficient cells were less sensitive to DNA-damaging compounds and showed an increased clearance of DNA damage. With further molecular analysis of the underlying processes, the researchers were able to show that the inactivation of USP48 in FA-deficient cells even restored a nearly error free repair of the damaged DNA.
Georgia Velimezi#, Lydia Robinson-Garcia#, Francisco Muñoz-Martínez, Wouter W. Wiegant, Joana Ferreira da Silva, Michel Owusu, Martin Moder, Marc Wiedner, Sara Brin Rosenthal, Kathleen M. Fisch, Jason Moffat, Jörg Menche, Haico Van Attikum, Stephen P. Jackson and Joanna I. Loizou. (#Co-first Author). Map of synthetic rescue interactions for the Fanconi anemia DNA repair 4 pathway identifies USP48. Nature Communications, June 11, 2018. DOI: 10.1038/s41467-018-04649-z.
The study was funded by the European Molecular Biology Organization (EMBO), the Austrian Science Fund (FWF), the European Commission, the European Research Council (ERC), the National Institutes of Health (NIH), Cancer Research UK, the Wellcome Trust and the Boehringer Ingelheim Fund (BIF).
Acute Myeloid Leukemia (AML) is an aggressive form of blood cancer that frequently develops in children. The diseased cells often carry mutated forms of a specific gene, which is known to function within large protein networks. Researchers at CeMM and LBI-CR identified a protein of this network crucial for the survival of the cancer cells – a novel potential approach for targeted therapies. The study was published in Nature Communications.
AML is not a single disease. It is a group of leukemias that develop in the bone marrow from progenitors of specialized blood cells, the so-called myeloid cells. Rapidly growing and dividing, these aberrant cells crowd the bone marrow and bloodstream, which can be fatal within weeks or months if the disease is left untreated. Myeloid cells of various types and stages can become cancerous and cause AML, which makes the condition very heterogeneous and difficult to treat. Thus, finding drug targets that affect as many forms of AML as possible is a prime goal for researchers.
The research groups of Florian Grebien from the Ludwig Boltzmann Institute for Cancer Research, Giulio Superti-Furga, Scientific Director of the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, and Johannes Zuber, from the Institute of Molecular Pathology, tackled that question in their latest study. They were able to identify common, conserved molecular mechanisms that drive oncogenesis in the context of the large number of different MLL-fusion proteins by characterizing the protein-protein interaction networks of distantly related MLL fusion proteins. Their results were now published in Nature Communications (DOI:10.1038/s41467-018-04329-y)
The scientists identified the methyltransferase SETD2 as a critical effector of MLL-fusion proteins. Using genomic techniques including CRISPR/Cas9 genome editing, the researchers found that SETD2 loss caused induction of DNA-damage and ultimately cell death in the cancer cells. Moreover, SETD2 loss increased the lethal effect of Pinometostat, a drug that is currently in clinical development for treatment of leukemia patients with MLL fusions. These experiments might pave the way for a more effective therapy in the future using a combination of compounds.
Anna Skucha, Jessica Ebner, Johannes Schmöllerl, Mareike Roth, Thomas Eder, Adrián César-Razquin, Alexey Stukalov, Sarah Vittori, Matthias Muhar, Bin Lu, Martin Aichinger, Julian Jude , André C. Müller, Balázs Győrffy, Christopher R. Vakoc, Peter Valent, Keiryn L. Bennett, Johannes Zuber*, Giulio Superti-Furga* and Florian Grebien* (*equal contribution). MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity. Nature Communications, 2018. DOI:10.1038/s41467-018-04329-y
The study was funded by the European Commission, the European Research Council (ERC), the Austrian Science Fund (FWF), the Austrian Research Promotion Agency (FFG), the National Institutes of Health (NIH), the National Research, Development and Innovation Office, Hungary, and Boehringer Ingelheim.
The first line of immune defense against invading pathogens like bacteria are macrophages, immune cells that engulf every foreign object that crosses their way and kill it with acid, in a process called phagocytosis. In their quest to systematically study proteins that transport chemicals across cellular membranes, researchers at CeMM characterized the critical role for transporter SLC4A7 in this process, providing valuable new insights for many pathologic conditions from inflammation to cancer. Their results were published in Cell Host & Microbe.
Among the many different kinds of immune cells that patrol the body, macrophages are the first when it comes to fight against a foreign threat. With their flexible and versatile surface, they engulf every microorganism or particle that could be harmful for the health of the organism, and enclose it in an intracellular membrane vesicle called phagosome. To eliminate the threat and break it down to its constituents, the interior of the phagosome needs to be effectively and progressively acidified. For this crucial part of phagocytosis, the macrophages must undergo multiple metabolic changes, which are not yet entirely understood.
The team of Giulio Superti-Furga, Scientific Director of CeMM, in collaboration with the laboratory of Nicolas Demaurex of the University of Geneva, discovered in their latest study that a membrane protein belonging to the family of “solute carriers” (SLCs) plays an essential role in phagocytosis and phagosome acidification. Their work was published in the journal Cell Host & Microbe (DOI 10.1016/j.chom.2018.04.013).
The researchers developed an essay with special cells in which they impaired the 391 human SLC genes individually using CRISPR/Cas9 gene editing technology. Strikingly, among all SLCs, SLC4A7, a sodium bicarbonate transporter, was the only one who turned out to be essential for macrophages to undergo phagocytosis and acidification. Cells with impaired SLC4A7 were unable to acidify their phagosomes and by consequence decreased their capacity to kill bacteria.
The results of this study do not only provide new fundamental insights into the molecular functioning of one of the most important cells of the immune system. As phagocytosis plays a significant role in various pathologic conditions from inflammation to cancer, these new insights are likely of relevance beyond the context of infectious diseases. The effort to understand the role of the different cellular transporters, supported by a grant of the European Research Council (ERC), has added a small new piece to the large and fascinating puzzle coupling trafficking of chemical matter to metabolism and cellular function.
Vitaly Sedlyarov, Ruth Eichner, Enrico Girardi, Patrick Essletzbichler, Ulrich Goldmann, Paula Nunes-Hasler, Ismet Srndic, Anna Moskovskich, Leonhard X. Heinz, Felix Kartnig, Johannes W. Bigenzahn, Manuele Rebsamen, Pavel Kovarik, Nicolas Demaurex, and Giulio Superti-Furga. The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification. Cell Host & Microbe, 2018. DOI: 10.1016/j.chom.2018.04.013
The study was funded by the European Research Council (ERC), the Austrian Academy of Sciences, the Austrian Science Fund (FWF), the European Commission, and the European Molecular Biology Organization (EMBO).
At the 12th CeMM Landsteiner Lecture, held by Yasmine Belkaid, Director of the NIH Center for Human Immunology and Director of the NIAID Microbiome Program, everything revolved around one of the most important emerging fields of research in life sciences: the microbiome. Yasmine Belkaid explained how microorganisms living in and on our bodies influence every aspect of our immune system, and why research in this field will change the medicine of the future.
We carry around nearly the same number of microbes as we have cells in our body, yet those microscopic symbionts express a hundred times more genes than human cells. This ratio, which Yasmine Belkaid presented at the beginning of her lecture, gave the audience a first impression of the magnitude of the microbiome’s influence.
The communities of bacteria, protists, fungi and viruses that reside throughout the human body affect many aspects of its physiology. However, the immune system is by far the most tightly interwoven part. Refuting the old paradigm of an immunity whose sole purpose is to defend the body against invading pathogens, Yasmine Belkaid showed how it constantly interacts with the commensal microbes and how those single celled organisms control the immune cells with a mind-blowing precision.
Among the many examples of her groundbreaking research, Yasmine highlighted the finding that single types of microbes are able to engage specific kinds of immune cells, like the CD8 lymphocytes which are promoted by S. epidermidis. Without causing inflammation, this specific interaction contributes to the protection of the skin against the infection with a pathogen. Yasmine Belkaid further described how “mysterious” non-classical MHC-I molecules present commensal antigens in the establishment of a homeostatic immunity and how CD8+ T cell inducing bacteria even promote wound healing.
To understand the profound alliance between the microbiota and the immune system in detail, Yasmine Belkaid concluded her talk, will be a major progress for combating a broad range of medical conditions, from infection to inflammation to cancer.
370 scientists of different fields and interested lay people showed with a long-lasting applause and many questions their appreciation of Yasmine Belkaid´s outstanding talk. The baroque festive hall of the Austrian Academy of Sciences was filled to the last place and many more followed the lecture via video stream in an adjacent room. Framed by the music of Bela Koreny and Ethel Merhaut, who delightfully performed two Viennese songs, the evening was rounded off with a cocktail reception and lively discussions.
Our warmest thanks to Yasmine Belkaid for this wonderful 12th CeMM Landsteiner Lecture!
Image Gallery CeMM Landsteiner Lecture 2018
Former CeMM Landsteiner Lectures
A video of Yasmine Belkaids Lecture will be available soon.
DNA mutations driving cancer development are caused by different mechanisms, each of them leaving behind specific patterns, or “scars” in the genome. Using CRISPR-Cas9 technology, researchers at CeMM and the Wellcome Trust Sanger Institute at Cambridge, UK were able to show for the first time in cell culture that specific genetic alterations indeed lead to the predicted pattern of mutational signatures observed in human cancers. The results were published in Nature Communications (DOI: 10.1038/s41467-018-04052-8).
When a cell develops into a tumor, something has gone terribly wrong: the uncontrolled growth, invasion of nearby tissues and finally metastasis are the result of many consecutive DNA mutations. Such an accumulation of demolished genetic material often derives from initial environmental exposures, enzymatic activities or defects in DNA replication or DNA repair mechanisms. Each of those initial mutagenic conditions creates their own pattern of DNA damage called mutational signature. Deciphering them could theoretically allow us to trace back the initial cause of a tumor, profile its properties and help find a therapeutic strategy.
However, reading those mutational signatures in tumor samples is a difficult task, as the large amount of mutations that a patient acquires during its lifetime create a noisy and uncontrolled system – even the best clinical data will, at most, provide only associations. Therefore, the group of Joanna Loizou, Principal Investigator at CeMM in collaboration with researchers from the Wellcome Trust Sanger Institute, developed an experimental setup to validate the concept of mutational signatures in cell culture.
The findings of this study not only confirm an analytical principle that describes mutational processes and cancer development, mutational signatures are a direct mechanistic read-out of specific dysfunctions of a cell. Thus, even if the underlying gene defect is unknown, mutational signatures could be used as biomarkers for the molecular characterization of tumors – a new diagnostic tool to improve the precise and personalized treatment of cancer.
Xueqing Zou*, Michel Owusu*, Rebecca Harris, Stephen P. Jackson, Joanna I. Loizou#, Serena Nik-Zainal# (*These authors contributed equally to this work # Corresponding authors). Validating the concept of mutational signatures with isogenic cell models. Nature Communications 9, 2018. DOI: 10.1038/s41467-018-04052-8.
The study was funded by the Austrian Academy of Sciences, the European Commission (Marie-Curie Career Integration Grant), the Austrian Science Fund FWF and the Wellcome Trust.
The 8th CeMM S.M.A.R.T. Lecture held by architect and urban design consultant Jan Gehl was exceptionally entertaining and inspiring. It illustrated with many captivating examples the problems cities developed in the 20th century by pursuing an object- instead of a people-centered city planning and how simple measures can make cities livable.
“We knew more about the natural habitat of the mountain gorilla or the Siberian tiger than about the Homo sapiens’ living space” – with this provoking citations, Jan Gehl displayed the vast lack of knowledge that lead to some of the 20th centuries biggest challenges for modern cities. By building in an objects- and road-focused manner, a typical approach for the era of modernism and “motorism” in architecture, urban planners forgot about creating livable spaces for people. Instead, huge buildings and vast roads were built for cars, a now outdated and inefficient transportation technology, as Jan Gehl pointed out.
In consequence, many modern cities today are not only ugly and unpleasant to live in, but also unhealthy. The emphasis on mobility, meaning the use of automobiles, lead to the so-called “sitting syndrome”, a lack of physical exercise that has become a mayor health threat. To counteract those developments, Jan Gehl pioneered an observation-based city planning by systematically documenting urban spaces, making gradual incremental improvements, then documenting them again.
His results are impressive: measures like banning cars from city centers, creating extensive and coherent biking lanes and designing nice and “sticky” places that people like to use, turned Copenhagen, where Jan Gehl was involved in the urban planning for over 40 years, from a car-dominated city into one of the most livable places in the world. Many other cities, including New York and Moscow, sought advice from Jan Gehl and improved their urban space with his help.
A crowded seminar hall at CeMM with an audience of somewhat 150 people with all kinds of backgrounds followed this S.M.A.R.T. Lecture eagerly and engaged in lively discussions afterwards. Artist, architects, city planners and scientists met Jan Gehl in the brain lounge for an intense discussion round. We are proud, honored, and most thankful that Jan Gehl followed our invitation, and supports our efforts to foster the interdisciplinary discourse, widen our horizons and establish a dialogue with the broader public. The quality of our research is strongly influenced by the quality of our environment and creativity flourishes in inclusive, integrative and livable cities.
His take home message will remain firmly etched into our memories: The world is not about getting from A to B, the world is about having nice places to be!
Lymphocytic choriomeningitis virus (LCMV) served as an indispensable model system for chronic viral infections over the last 80 years; two Nobel prizes were awarded for its exploration. However, the molecular interactions during the life cycle of the virus were hitherto poorly understood. In a new study, published in PLOS Pathogens, CeMM scientists revealed the comprehensive set of cellular proteins that physically interact with the LCMV polymerase – a key enzyme for the development of a chronic infection.
Chronic viral infections like HIV or hepatitis are among the biggest threats to human health worldwide. While an acute viral infection usually results in a full recovery and effective immune memory, chronic viruses evade the immune system and remain permanently in their host´s body. Treating such a disease is a difficult task, as the molecular events during the development of a chronic infection remained largely elusive.
With their latest study published in PLOS Pathogens (DOI 10.1371/journal.ppat.1006758) the team of Andreas Bergthaler, Principal Investigator at CeMM, in cooperation with the University of Basel and the MRC Laboratory of Molecular Biology Cambridge made an important contribution to the understanding of chronic viral infections: the scientists established the first comprehensive overview of cellular proteins interacting with the LCMV polymerase, a crucial enzyme for the replication of the virus and for chronic infection. By mapping them in the human proteome, they revealed various viral strategies and potential targets for future antiviral therapeutics.
In order to perform the study, the researchers – with CeMM PhD student Kseniya Khamina as first author – developed a novel approach to tag viral proteins. Therewith, the interactions of the LCMV polymerase with the proteins of the host cells were determined. Combined with publicly available data from other RNA viruses’ polymerase interactomes, the generated dataset allowed a mapping of the cellular pathways targeted by different viral polymerases. Some of the proteins found to interact with the LCMV polymerase turned out to be essential for the viral life cycle.
Kseniya Khamina, Alexander Lercher, Michael Caldera, Christopher Schliehe, Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, Anannya Bhattacharya, Peter Májek, Alexey Stukalov, Roberto Sacco, Leo C. James, Daniel D. Pinschewer, Keiryn L. Bennett, Jörg Menche, and Andreas Bergthaler. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLOS Pathogens, December 20, 2017. DOI: 10.1371/journal.ppat.1006758
The study was funded by the City of Vienna and the Austrian Academy of Sciences.