Congenital immunodeficiencies comprise a group of disorders characterized by an abnormal immune system. The body’s ability to fight infections is impaired and infections can have life-threatening consequences for those affected. Analysis of patients with a disease characterized by an inherited lack of neutrophil granulocytes termed severe congenital neutropenia (SCN) may shed light on the delicate balance of factors controlling differentiation, maintenance, and decay of neutrophils. The team of CeMM Principal Investigator Kaan Boztug in collaboration with the group of Christoph Klein, Director of the Dr. Von Hauner Children’s Hospital Munich, identified mutations in the gene JAGN1 as a novel subtype of SCN in 14 patients bearing 9 distinct JAGN1 mutations. JAGN1 deficiency accounts for approximately 10% SCN for which the underlying genetic defect had previously been unknown. The researchers could show that JAGN1 mutations lead to aberrant function of the endoplasmic reticulum, defective protein glycosylation and increased neutrophil apoptosis. SCN patients are usually treated with the cytokine G-CSF, however for JAGN1-deficient patients the treatment response was unsatisfactory. In a second study IMBA Director Josef Penninger and his team generated Jagn1 knock-out mice and could show that GM-CSF, but not G-CSF, treatment rescues the defects of JAGN1-deficient neutrophils in mice.
Kaan Boztug, first author of one of the studies, identified the first patients with JAGN1 mutations: “The discovery of the JAGN1 deficiency illustrates that inborn errors of immunity can be caused by mutations in genes that were previously not even known to play a role in the immune system. It would be a wonderful result of this CeMM-IMBA-Munich collaboration if treatment with GM-CSF also works for human patients – this will now be assessed in further clinical studies. This is also a perfect example that not only new drugs lead to better therapies. An enhanced molecular understanding of diseases may enable targeted use of existing drugs and can thus fulfill the promise of patient-oriented medicine."
The findings of both studies have been published on August 17, 2014, in the journal Nature Genetics:
Boztug, K. et al. JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. Nat Genet. (2014).
Wirnsberger, G. et al. Jagunal-homolog 1 is a critical regulator of neutrophil function in fungal host defense. Nat Genet. (2014).
Genetic requirement for drug action is important to study as it may reveal mechanism of drug resistance, particularly in cancer, as well as generate ideas for better, safer and more personalized drugs. The laboratory of CeMM Director Giulio Superti-Furga used a genetic screen with human haploid cells, based on the work of Thijn Brummelkamp and his team (NKI and CeMM Adjunct PI), to identify the genes affecting the action of a poorly understood cancer drug under clinical evaluation. Surprisingly, only one gene turned out to lead to resistance, the uncharacterized member of the solute carrier SLC35F2. Further studies showed that whether this cancer drug works or not is entirely dependent on the presence of this transporter. In fact, there is a strong correlation between the levels of expression of the transporter and sensitivity to the drug. If the door is open, the drug will go through and kill the cell.
The findings have been published advanced online in the journal Nature Chemical Biology: The solute carrier SLC35F2 enables YM155-mediated DNA damage toxicity. Georg E Winter, Branka Radic, Cristina Mayor-Ruiz, Vincent A Blomen, Claudia Trefzer, Richard K Kandasamy, Kilian V M Huber, Manuela Gridling, Doris Chen, Thorsten Klampfl, Robert Kralovics, Stefan Kubicek, Oscar Fernandez-Capetillo, Thijn R Brummelkamp, Giulio Superti-Furga. Nature Chemical Biology. doi:10.1038/nchembio.1590.
SLC are the neglected gates that regulate access to biological systems to chemistry, or of organisms to the environment. CeMM is dedicated to mount a large interdisciplinary effort involving several laboratories to try to crack the “code” of the transport and regulation specificity. This will take several years but will allow to have better targeted drugs, that are safer because they know where they go, and to understand the relationship between drugs and nutrition.
On Friday, July 25, the new research report was presented to a selected audience on the CeMM terrace.
The concept of the current report is a wonderful example of our dialogue with society. Our befriended artist, Dorothee Golz, approached us with the idea of having a geneticist collaborate with her to unravel the traits in a particular branch of the body of her oeuvre that allows for a proper “genealogy”. What ensued is presented in this report and represents what we believe may be a first-ever formal quantitative representation of the relationship among the works of an artist. The concept can be expanded to describe also other artistic and scientific output.
To request a hardcopy please send a message to office(at)cemm.oeaw.ac(dot)at
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.
Are you full of ideas and impatient for action to translate the opportunities of the genomic age into better therapeutics and diagnostics? Do you have a truly collaborative mindset and enjoy teamwork across disciplines? Do you have an inclusive and open personality that cherishes being a scientist within a broader cultural and social context?
CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, is one of the best places you should consider to advance your basic, medical-oriented research.
With great pleasure we announce that Denise Barlow, Principal Investigator at CeMM and Honorary Professor of Genetics at the University of Vienna, has received the Erwin Schrödinger Prize 2014 for lifetime achievements. The Erwin Schrödinger Prize is an annual award presented by the Austrian Academy of Sciences for lifetime achievement in the fields of mathematics and natural sciences. This prize is the most prestigious award of the Austrian Academy of Sciences and was established in 1958.
This recognition is very well-deserved. Denise Barlow's contributions to the field of mammalian genetics as well as to Austrian research are exceptional. She is a world-leading expert in epigenetic mechanisms operating in development and disease. We congratulate Denise!
In 1991, the Barlow group discovered the first mammalian imprinted gene (Igf2r) and since then, has uncovered many details of the imprinting mechanism and promoted its use as an epigenetic gene-regulatory model. Her laboratory has shown that an unusual and very long non-coding RNA (lncRNA), a macro ncRNA, induces imprinted gene expression. More recently, her laboratory has also shown that transcription, independent of the lncRNA product, is the mechanisms that silences the Igf2r gene. The focus of her work currently is to understand the epigenetic processes by which these unusual macro-ncRNAs induce gene silencing in imprinted clusters and in the wider mouse and human genomes.
July 06 - 08, 2014 More than 40 speakers, session chairs and special guests together with guests representing the Austrian molecular biology and life sciences community celebrated the 50th and 40th anniversaries of the European Molecular Biology Organization (EMBO) and the European Molecular Biology Laboratory (EMBL) and their impact in Austria, with a dedicated event. EMBanniversary AUSTRIA, a unique fusion of a scientific conference, alumni reunion, party as well as science & society and political stakeholder event, started with a Sunday evening Welcome Bash on the terrace of the CeMM – Research Center for Molecular Medicine on July 6, followed by a two-day conference in the beautiful Jesuitensaal of the Aula der Wissenschaften in Vienna’s 1st district.
The conference included 7 scientific sessions, thematically named after eminent Austrian scientists such as Gödel, Landsteiner, Perutz or Mendel, with speakers and session chairs that have direct links to EMBO and EMBL, either through past employment, prizes or fellowships and that furthermore also have a direct link to Austria. EMBL Director General Iain Mattaj delivered the Wittgenstein Lecture entitled “Looking into the future of molecular biology through the EMBL lens”. A second special lecture, the Freud Lecture, was delivered by the IMP’s former director Kim Nasmyth of the University of Oxford.
Giulio Superti-Furga, Chair of the Board of the EMBL Alumni Association, on behalf of the association’s Austrian Chapter, presented the association’s Austrian Chapter Achievement Award Medal to Max L. Birnstiel, former director of the Institute of Molecular Pathology, and Denise P. Barlow, Principal Investigator at CeMM in recognition of a life-time of outstanding research in molecular biology and for their contributions to the EMBO and EMBL community in Austria.
The award ceremony was followed by a lively round table panel discussion on “How to Promote Molecular Biology?” chaired by Giulio Superti-Furga. The panelists Maria Leptin (EMBO Director), Hemma Bauer (Austrian Ministry of Science, Research and Economy) and Renée Schröder (Max F. Perutz Laboratories, Vienna) inspired, challenged and engaged the audience in a vibrant debate about the role, impact and future of molecular biology and the significant role of life sciences research in Austria.
EMBanniversary AUSTRIA was rounded up by a wine and cheese reception that provided additional opportunity for video interviews, networking and reminiscence. Many guests expressed their excitement with respect to the opportunity to meeting old friends and hearing cutting-edge science from Austrians involved in the diverse areas of the life sciences field. We thank all speakers and participants for their contribution to a successful and enjoyable event.
We gratefully acknowledge the following sponsors for providing additional support for EMBanniversary AUSTRIA: EMBL Alumni Association, EMBLEM Technology Transfer GmbH, Austrian Federal Ministry of Science, Research and Economy, Research Institute of Molecular Pathology, Austrian Academy of Sciences, Boehringer Ingelheim RCV GmbH & Co KG, Haplogen GmbH, Starlab GmbH, Max F. Perutz Laboratories, Sigma-Aldrich Handels GmbH and Biozym.
Happy birthday EMBO! Happy birthday EMBL!
The Austrian Academy of Sciences (ÖAW) has announced their newly elected members. Among them are two Principal Investigators of CeMM. We congratulate Sylvia Knapp for being elected as Corresponding Member and Sebastian Nijman for having been named as member of the Chapter of Young Scientists (“Junge Kurie”). Giulio Superti-Furga, Scientific Director of CeMM: “We are very proud of the scientific excellence of the two group leaders. This recognition by the Austrian Academy of Sciences is very well-deserved.”
The 8th CeMM Karl Landsteiner Lecture at the beautifully frescoed Festive Hall of the Austrian Academy of Sciences was delivered by Prof. David M. Sabatini of the Whitehead Institute for Biomedical Research of the Massachusetts Institute of Technology (MIT). More than 350 scientists and interested lay people from all walks of society attended the lecture, which was opened by CeMM’s Scientific Director Prof. Giulio Superti-Furga, who acknowledged Prof. Sabatini’s distinguished achievements and leading contribution to molecular biology. Gustav Ammerer, a Viennese biotech pioneer, research group leader at the Max F. Perutz Laboratories (MFPL) of the University of Vienna and accomplished amateur cello player provided a smooth start of the evening with his interpretations of Johann Sebastian Bach’s Suite No.1 in G major (BWV 1007), Allemande & Sarabande. David M. Sabatini continued the series of world-leading distinguished scientists of CeMM Karl Landsteiner lecturers that started in 2007. Prof. Sabatini, MD, PhD, recipient of the 2014 National Academy of Sciences Award in Molecular Biology, is the leading investigator on what can be considered probably the most “critical” biological process, the regulation of cellular growth and metabolic state, and its master regulator protein “mTOR” with its essential role in cellular decision making. In his talk “Grow – Shrink, Get Fat – Stay Lean, Divide – Rest: How Cells Decide” Prof. Sabatini outlined the fundamental and intriguing processes surrounding the mTOR protein that cells use to integrate internal and environmental cues such as nutrient availability to rationalize cellular decision making such as proliferation or differentiation. In his presentation he also introduced some of his latest research findings and discussed challenging open questions. The lecture was very well perceived as evidenced by a lively podium discussion and rounded up by a cocktail reception in the academy’s aula. We are grateful to Prof. Sabatini for his fascinating presentation.
Mutations of CALR have been discovered recently in an estimated 15% of cases of myeloproliferative neoplasms (MPNs - a group of blood disorders involving overproduction of blood cells) by the research team of Robert Kralovics at CeMM and collaboration partners at the Medical University of Vienna (NEJM doi: 10.1056/NEJMoa1311347). QIAGEN now licensed the technology from CeMM, and will develop a reliable diagnostic test for the CALR mutations offering each patient a clearer prognostic profile and guiding disease management. Development of a CALR diagnostic test will be highly complementary to QIAGEN’s kits for a key mutation of the Janus kinase 2 (JAK2) gene.
Lange Nacht der Forschung (Long Night of Science) 2014
(Vienna, 4 April 2014) Counting more than 135.000 visitors of all ages the ‘Lange Nacht der Forschung’ (Long Night of Science) 2014, a joint initiative of the Federal Ministry of Science, Research and Economy (BMWFW) and the Federal Ministry for Transport, Innovation and Technology (BMVIT), took place on Friday 4th April, at several locations throughout Austria. CeMM´s booth at the Aula der Wissenschaften in Vienna’s first district with about 3.200 visitors was a significant success. CeMM was represented with an information stand that also included a ‘hands-on’ science parcours with stations that allowed visitors to extract DNA from strawberries, learn how to build a DNA double helix with gummi bears and toothpicks, a pipetting competition and a microscopy station. The CeMM Management and CeMM scientists, among them Principal Investigators Joanna Loizou, Andreas Bergthaler, Kaan Boztug and Christoph Bock were present on site and excited by the overwhelming interest. “The last teenagers, who still wanted to look through the microscope, literally had to be politely rejected at 10 past midnight – what a night, what a sight!”, Bergthaler summed up. Last but not least the good news of the evening rounded up the successful event, when the Federal Minister for Science, Research and Economy, Reinhold Mitterlehner, announced that basic science in Austria is not threatened by budget cuts.