Science Life Facts

Research Report 2017 Research Report 2017 Science Life Facts The image on the cover of this research report, captured by the CeMM faculty in Lower Austria, was part of the “CeMM Blue Book Challenge”.

What is the CeMM Blue Book Challenge?

We document our experiments, findings and thoughts in our lab journals, aka “blue books”. Appropriately, the first ever CeMM research report in 2007 imitated a blue book to clearly symbolize that we report our results to the public in an authentic and comprehensive way. We have a growing number of friends, supporters and VIP’s captured on camera with our blue books to symbolize our deal with society.

Last year, for CeMM’s 10th anniversary, we went one step further and used the original linen cloth cover for our report and then asked the CeMM community to participate in what we called the “CeMM Blue Book Challenge” – this involved taking a creative picture of/with the Blue Book and submitting it into the following categories:

Category 1: Most faraway place Science (relative to CeMM, that is) Category 2: In front of a landmark Category 3: In everyday life Category 4: Doing/watching sports Category 5: At an event Category 6: Still life Category 7: With VIP

Category 8: With the “number 10” Life Category 9: Flashmobbing Category 10: Photobombing Category 11: In a holiday/relaxing setting Category 12: Anything else creative

We were overwhelmed by the creativity, ­virtuosity, humor and the richness of ideas reflected in the numerous submissions. They were ­exhibited at our 10th anniversary Facts ­celebration in September 2017.­ However, to reiterate our gratitude for the incredible response to our call and to thank every participant for his or her effort, dedication and CeMM spirit, we would like to start off this research report by presenting the submissions for the Blue Book Challenge. Facts Life Science CeMM Research Report 2017

Introduction pp. 10–13

Science at CeMM

Molecule Man/Drugs pp. 16–23 Bloody Lady/Personalized Medicine, Rare Diseases pp. 24–35 Monsieur Macrophage/Immunity pp. 36–43 Virus/Infectious Diseases pp. 44–51 Miss DNA/Genome Based Medicine pp. 52–59 Cancer pp. 60–67 Facilities at CeMM pp. 68–69 Principal Investigators pp. 70–79 Scientific Advisory Board pp. 80–83 Obituary pp. 84–85

Life at CeMM

Testimonials pp. 88–99 Science Lectures, Symposiums and Workshops pp. 100–105 Social Events pp. 106–109 10 Years of CeMM pp. 110–119 Community Service pp. 120–121 Art and Science pp. 122–123

Visits to CeMM pp. 124–125 Life Awards pp. 126–127

CeMM Facts

Co-Workers pp. 130–139 Facts & Figures pp. 140–143

Publications 2017 pp. 144–149 Facts CeMM Ph.D. Program pp. 150–151 Responsible Research Lectures p. 152 Libra Activities p. 153 Technology Transfer p. 154 Strategic Partnerships and Collaborations p. 155 Supporters pp. 156–164 How to Reach CeMM p. 165 Acknowledgements pp. 166–167 Imprint p. 168 The Mission of CeMM 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 characterized by 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 Science arts. CeMM trains modern biomedical scientists to make great contributions. The goal of CeMM is to pioneer the science that nurtures the precise, personalized, predictive and preventive medicine of the future. Life Facts Giulio Superti-Furga ­Anita Ender and CeMM Directors 2017 Research Report Introduction

You hold inyour research hands annual the 10th Vienna that strongly that ­ Vienna We for the doresearch benefit scientific of with the “new” Medical ­ Medical with the “new” EMBL/EMBO ­ found that their of circumstances, By aseries Molecular Medicine of the Austrian Academy of of the Austrian Medicine ­Molecular particular individuals in the Austrian Academy inthe Austrian individuals ­particular What dowedo? years ago, ago, 30 years the founding of the IMP e.g. ment, and of Vienna University by the Medical run hospitals, and teaching-active research- largest numerous historical roots inthenumerous vision historical of for Center the Research of CeMM, report matured to a CeMM-unique success formula, formula, success aCeMM-unique to matured of engagement science; and ethical research solutions;medical commitment responsible to investment inyoung scientists; development our as serve that principles ten ­formulated we Forour tenth anniversary ­medicine. We­medicine. you thank allhere. for ­ ­ research- City of Vienna. of Vienna. the City that occurred in September 2017. They were 2017. inSeptember occurred that celebrations theanniversary underpin to 10th center into recognized CeMM aninternationally by genetic inheritance and ­ by genetic inheritance inthe middle located being of one of the world’s Sciences. The Austrian Academy of Sciences is Academy of Sciences The Austrian Sciences. supportive ministry, IMBA’s example,a supportive the ministry, IMBA’s all they could ­ to part of our mission part are and statement used were of developing institute, into auniquely fortunate the had luck has CeMM inthe past, of Sciences our mother We institution. of have the privilege of new technologies; elaboration of personalized centered around a wonderful event, which ­centered around event, awonderful A­ ­ecosystem. creation; social engineering of a new culture of of anew culture engineering creation; social guides: operative maximum innovation; ­current ­ ceutical super-cooperation. have ingredients ten These and impact commercialization active ­society; quality and excellence; focus on medicine; and on excellence; medicine; focus quality creation for of basis theprecision scientific industry that sustains the research the research sustains that industry supporting administrators have donesupporting administrators formidable team of and scientists team formidable community, the energy associated community, associated the energy leverage the privilege and grow the privilege leverage values science, a local pharma alocal science, values University, the City of University, the City attractive environattractive - ­ We and who supporters allour friends thank They will also serve as guides through this report. guides thisreport. through as alsoserve They will by Business CompanyTheatre (directed would have attended the celebration of this with particular joy and pride was Principal Principal joy and was pride with particular presentwere many too and be to contributed, Denise’s students, was a serene appraisal of aserene appraisal the was students, Denise’s Dr. Häupl, Michael who unable while being to Dr. ­ Investigator Denise Barlow.­Investigator Denise to acknowledge 2017. Denise was a stellar presence at CeMM from from astellar presence at CeMM was Denise 2017. research: Miss DNA, Monsieur Macrophage, Monsieur Macrophage, DNA, Miss research: ­representing one fields main of CeMM’s of from CeMM in the last ten years. A person who Aperson years. ten inthe last CeMM from who students graduated all50Ph.D. ­featuring Cancer, Bloody Lady, Virus and Molecule Man. and Man. Molecule BloodyCancer, Lady, Virus intellectual and ­ intellectual institutions. The memorial service, lovingly The service, memorial ­institutions. named. We thank the Austrian Federal President, President, We Federal named. the thank Austrian and whoincluded colleagues many have friends inspiring us for us many more come. to ­inspiring years tool. The “Walking Acts” of the Open House of House the Open Acts” The “Walking tool. the field genomicof She imprinting. also accrued not only bringing the her beginning, ­ Sadly, Denise died of lung cancer on October 21, 21, onSadly, of October died cancer lung Denise achievement in teaching, training and ­ training achievement inteaching, attend the event, honoredattend the event, withtheir visit us a ­ accompanied years, over ten the us past and­ generous a whole of of ­ badges series Many supporters,colleaguesandfriends orchestrated by ­ orchestrated Europe’s majorof Europe’s ­ group female several in leader the first, often ­ group, as music quiz and ascience celebration. Each actor embodied a character acharacter embodied actor ­celebration. Each colleagues from all over the from colleagues world and most of scripted piece performed at the anniversary at the anniversary piece performed scripted thereafter, inaugurating the “hall of fame” of fame” the “hall inaugurating soon thereafter, scientists can ­ can ­scientists scientific acumen and experience as pioneer and in experience acumen ­scientific displayed their exquisite acting skills in a short, inashort, displayed skills their exquisite acting Alexander Van der Mayor, Bellen and Vienna’s develop around charismatic personalities. Denise will keep will Denise personalities. Sylvia Knapp and attended by affectionate community that that community affectionate molecular biology research biology research molecular honor by avocal, being sponsoring sponsoring amazing amazing mentoring theater) ­theater)

theater theater

Ce — M­—M­— Research Report 2017 Facts Life Science Science 10 11 We allthose to who and visited thankful are was the overhaul of the CeMM building’s the overhaul of was year building’s the CeMM with a performance to celebrate to the “ with aperformance world leaders in this important field. Christoph world field. inthisimportant leaders Austria’s most beautiful buildings of the neo buildings most beautiful ­Austria’s Again, it was a year of many grants, awards and awards of ayear many grants, itwas Again, Josephinum for amemorable began that evening BioMedical Research (NIBR), Hermann Hauser, Hauser, Hermann (NIBR), Research ­BioMedical Bundesimmobiliengesell­ hosted many CeMM memorableIn 2017, Lounge. In September, we partnered withthe we InSeptember, partnered Lounge. Bock and his team are avolcano are andBock histeam of innovative the achievements of recognizes anearly Prize (EIC) and Jean-Pierre Bourguignon, the Bourguignon, President and(EIC) Jean-Pierre to fulfillingourmission previous prize holders alldeveloped­previous prize into the ­ Ernst foyer. architect to We grateful are CeMM design expert Kriso ­ Kriso design expert CeMM the legendary serial entrepreneur who scientist serial the legendary forthe President Institutes of the Novartis Computational Biology (ISCB). The ­ for Computational Biology (ISCB). medical doctors and philosophers. doctors medical exhibition onheart” the of premises one of this improvement universe Also,our art possible. Christoph Bock by the International Society by Bock Society the International ­Christoph honors. We would pick to like out one we that mid-career scientist for outstanding for scientist outstanding mid-career to Scientific highlightsthatgetuscloser Symbolically important in this anniversary inthis anniversary Symbolically important and our young faculty. at theare forefront of innovation, Jay like Bradner, artwork by Hans Kupelwieser by Hans for artwork the Brain awarded to CeMM ­ awarded CeMM to 2017 proud Prize the of: Overton particularly are approaches genomes for decoding and of the European Research Council (ERC). Council of the Research European of the two communitiesof ­ well the two as as members with various Lounge, out Brain CeMM far times inthe indifficult and sciences on art expanded and now new includes awonderful the Innovation new European chairs Council ­epi classical era, and ended withalively era, ­ classical ­contributions computational to biology. The and visitors, among and which visitors, ­speakers people who dedicated time to our students, our postdocs our postdocs time our to students, ­dedicated ­genomes, alsoat the level. single-cell Principal Investigator Principal schaft BIG for BIG making schaft Leinfellner and Leinfellner journalists, journalists, discussion discussion artificial ­artificial

Overton Overton Kopper, ­ “pharmacoscopy”, as itallows monitor to as the “pharmacoscopy”, vivo” and the results can contribute rapid vivo” “ex and thecan results “DNA wounds” are created to test or test to wounds” repair created are “DNA While still in the experimental phase, it inthe experimental can still be While With the adventWith where of genomic engineering, with cancers of the The blood. method, termed with cancers was able, in 2017, together with the Medical together withthe able, in2017, Medical was University of Vienna, itsclosest partner, to of Vienna, ­University It is with the reassurance of on being the right It iswiththe reassurance Investigators. The interplay between The interplay between Investigators. ­Principal Investigators, as 2017 has been the been of beginning has 2017 as ­Investigators, mounted has large Loizou ­Investigator Joanna Principal CeMM Luckily, years, inthe past In fact, the interpretation of the the interpretation genome-encoded In fact, (such as UV light) but also with stress caused by caused but UVlight) alsowithstress (such as uses computer-based image analysis, exploiting computer-baseduses analysis, image precision medicine, as the effect of drugs is of drugs the effect as medicine, ­precision precision and personalized medicine for patients medicine andprecision personalized ­ and and individual- properties the tissue- in the choice of therapeuticline. the next into take the that physician can information the rapidly to visualize machine learning, on the­tested blood of patients individual onlight the subtle yet interplayamong essential mention among here, Principal the CeMM numerous unfortunately, invasion and, human viral cellmetabolic imbalance, division, hasty track in terms of societal mandate, that CeMM CeMM that mandate, of societal interms track that could compensate for specific genetic couldthat compensate for specific the publication of a series of studies that shed that the publication of studies of aseries is the genome. thisintegrity to Achallenge the ­ the environ­ these human defects. Joanna finds particular finds Joanna particular these human defects. account along withmany other considerations associated not only withenvironmental forces­associated on the cells malignant and not on healthy cells. genome integrity pathways and describe drugs drugs and describe pathways genome integrity genomes, epigenomes, metabolism, disease and disease genomes, epigenomes, metabolism, function, there isarenewed interest in gene function, effect of pharmaceuticals under the of microscope, pharmaceuticals effect considered a particularly “practical” form of of form “practical” considered aparticularly ­contribute ahighly innovative approach towards efforts to systematically investigate the investigate role of systematically to efforts ­center of and involve activities many CeMM all epigenetic “reading mode” imposed epigenetic by “reading specific differential effect of potential drug treatments of potential drug effect ­differential ­deficiencies. drug action is the subject of action isthe most subject of ourdrug projects. disorders associated with defects in DNA repair. inDNA withdefects associated disorders processes that safeguard the integrity of the integrity safeguard that processes ment more are at the ever than Thank youSylvia Knapp work, which closer even ties helped build to us and medical for on responsibility taking years, we will expand core on competenceswe will these CeMM word “drugs”, as traditionally it has been the been ithas traditionally as word “drugs”, will come. will A few years ago, CeMM and the Medical and the CeMM Medical ago, years A few University of Vienna signed acollaboration of Vienna ­University Ultimately, bekey to thiswill we thinkthat Director of Medical Affairs for the three initial Affairs Medical of Director Funds were specifically dedicated by the Ministry Ministry by the dedicated specifically were Funds In the past ten years, CeMM has achieved more has CeMM years, ten In the past Minister Dr. Töchterle­Minister at the this time) fuel to precision medicine avenues. The very heart and heart The avenues. very medicine ­precision prerogative of­prerogative pharma in new ­ framework agreement to allow the mutual use agreement allow to use framework the mutual application, technology through its research to invent mandate new our societal ­fulfilling the pharmaceutical industry and in industry in theleaders pharmaceutical thank Sylviathank for her commitment and dedicated CeMM: Haplogen, MyeloPro and Allcyte. More Haplogen, MyeloProCeMM: and Allcyte. come, to Inthe years ­therapeutic opportunities. the Medical University of Vienna, was appointed was of Vienna, University the Medical we expected in terms of proposing new interms we expected than talents and build cutting edge infrastructure. infrastructure. edge and cutting build ­talents new recruit to community medical the Viennese but CeMM also fosters a translational impact of atranslational alsofosters but CeMM between organizations, Sylvia Knapp, CeMM PI Sylvia PI Knapp, CeMM organizations, between ­biotech companies spun been off from have sofar and ­ to academia, ­ ­academia, partner with the Medical ­ withtheand Medical partner a new ­ and is an essential and long-serving part of our part and and isanessential long-serving existing chemical entitiesand chemical existing for medical Focus ontherapeutics CeMM Ph.D. program. We program. wouldof to Ph.D. like the CeMM specific infrastructure, further strengthening strengthening further infrastructure, of specific of Science and Research (headed by Federal (headed by and Federal Research of Science ethical issues related to CeMM and coordination CeMM relatedto issues ethical creativity should besummoned­creativity and bundled ­continue Investigator at CeMM bePrincipal to consideration. We used to be afraid to use the use to ­consideration. We beafraid to used collaboration. As avisible and link As important collaboration. soul of CeMM is free-minded scientific research, research, scientific soul isfree-minded of CeMM since 2006and Biology at Professor of Infection scientific collaboration­scientific and common projects. spin-off companies and out-licensing. Three discover and develop­discover We them. to now subscribe paradigm, ­ paradigm, implement Sylvia will new standards. alliances to ­ to alliances according to whichaccording to the uttermost supported by other innovative discover and developdiscover new ceutical companies­ceutical to University and University “CeMM teenage years”. These are notoriously are These years”. teenage “CeMM We care, we share. Please, consider how Please, you We can we share. care, We you ask inallpossible support to ways. us We would become to in like yet more daring The Rector of the Medical University of Vienna, of Vienna, University of theThe Medical Rector working together and rely on hundreds Anita Ender Anita Markus Müller, them the called upcomingMarkus patients. patients. ­powertogether of innovativeresearch scientific potential lack of focus and often self-centered and often ­potential of lack focus Giulio Superti-Furga Graz. In future, the various collaboration tasks collaboration tasks the various Infuture, Graz. faculty and team leader and shoulders, on team acase-by- ­faculty of University role of the in the Medical Senate her We on her new faculty. alsocongratulate CeMM is now starting its second decade of life. of itssecond life. decade isnowCeMM starting that we can, slowly but we can, that surely, celebrate the innovation. We­innovation. of withnew ways experiment innovation goeshand inhand withsocial improving, rather than relaxing our standards. relaxing ourimproving, standards. than rather We But alsoidealism. committed are narcissism. on different bedistributed the will new campus relating to of Vienna University the Medical ­ to CeMM continuesCeMM beaplace to where biomedical terms of and inventions ideas terms and yet more acceptingto of the adolescence challenges and Support usduringourseconddecadeoflife and help improve the well-being of many future also contribute multiplying to so these efforts and coordination activities between CeMM and CeMM and coordination between activities of case basis. basis. case difficult years, marked by identity crises, a marked crises, by identity years, ­difficult disciplined and effective intheir implementation. and­disciplined effective

colleagues and partners beyond and­colleagues partners our walls succeed withcomplex, ambitious projects. “­ Vienna English Theater ­science chapters. The through thefollowing Lady will guide you ­Macrophage and Bloody Miss DNA, Cancer, Monsieur Molecule Man, at our 10th anniversary ­research fields of CeMM. ­represent themain by the ­celebrations, ­ characters, Walking Acts” from the ­actors of the ­embodied symbolically ­Virus,

Ce — M­—M­— Research Report 2017 Facts Life Science Science 12 13 Science at

CeMM Science Life Facts Molecule Man: Ladies and ­Gentlemen – I give you the power of drugs. Not only will there be drugs to improve your arm ­wrestling skills, oh no! I have a Molecule Man dream that one day there will be drugs that are personalized, ­precise; they will be part of a + Drug Combinations from the CLOUD ­preventive medicine that takes the organism and its metabolism + A Microscope for Drug Discovery as a whole into account… Monsieur Macrophage: Eh… what are you doing? Molecule Man: A victory speech. Life Facts from GiulioSuperti-Furga’s lab with theintro­ scientists or physicists, we madesubstantial special algorithms that exploremachinelearning. small blood samples. trademark working modeof super-cooperation, the CLOUD, Kubicek’s team was able to find a the diversity of structures and molecular targets the CeMM library of uniquedrugs(CLOUD), a which connectsscientistsof different fieldslike gical advances of thepast years, and usingour Finding therightdrugfor therightpatient is It enables immunomodulatory drugdiscovery an example, Stefan Kubicek areas. By taking advantage of theswifttechnolo one of themaingoals of personalized,precise duction of pharmacoscopy, a novel­ of all FDA-approved chemical entities. Using ­collection of compounds that effectively progress intranslational researchin2017. As biologists, physicians, chemists, computer medicine – and oneof CeMM’s mainresearch microscopy with single-cellimage analysis and method combininghigh-throughput ­ prostate cancer. Another interestingstory came novel drugcombination highly effective against by analyzing immunecell­ interactions in ’ s teamdeveloped micro­ fluorescent ­represent scopy - broad range ofthe approved broad range drugs? able are that hundred cover to a few substances But how platform. find to screening chemical highly­microtiter by ­ CeMM’s plate used at the time same fit on asingle standardized on and the market, of most drugs targets cular and mole of structures represent the diversity ­collection of compounds could that effectively a create to the idea was and Enamine Kiev: the University Uppsala of Vienna, University collaboration with­ problem that in tackled Investigator at CeMM Kubicek, chemist and Principal Stefan needed. asimpler solution ofinteractions drugs, was for screening synergistic asystematic To facilitate beconsidered adaunting can task. agencies approved products by drug the regulatory 30,000 among thefor more a given disease than anoveloptions. Finding combination of drugs new therapeutic reveal can setting experimental inan assessed combinedtwo pharmaceuticals of the synergy of mixing drugs, the unsupervised ­However, strongly while doctors advise against on patient leaflets. information warnings from compounds wellthe known separate –afact of theoutcomes effect from largely deviate that sometimesTwo together can to lead taken drugs found at CeMM asolutionresearchers for thisproblem. buta small comprehensive of molecules, representative library By creating biologicalchallenge. setting isagreat inaspecific effect incombinationcompounds, other, witheach especially for their However, the screening thousands of approved scratch. from drug and development the expensive to tedious an alternative of anew combinations be or can drug drugs existing to Giving new purpose the CLOUDCombinationsDrug from scientists from the Medical the Medical from scientists automated ­ the active form ofthe prodrugs. form active all FDA-approved including entities, chemical representing – theCLOUD world’s library first of 308compoundstotal for the selected were become to a active), need bemetabolized to otherwise (that of prodrugs forms 35 active and withunknown targets drugs bined with34 Com those classes. from selected were drugs 239representative algorithm, a clustering With and activity. structure of similar classes 176 and grouped themknown into targets molecular with ­appended biological alldrugs to activities the plate, researchers screening 384-well their aimof the fitting collection on a standard ­collection), the work reach to begun: just had “STEAM” (the molecules small so-called active systemically 954 the remaining With well. as discarded were foundare creams like only intopical products, or diseases not treat are to used interactions, other mechanisms protein-ligand through than All ­ fragments. salt well as as the list, from bodies they removed macromolecules anti like large withidenticalproducts compounds. Next, all discarding the database, from ingredients unique pharmaceutical active 2,171 extracted and Kubicek’s determined necessary. team was of condensationseries a step, In afirst steps molecules that exert their biological exert that molecules effects - ­

Ce — M­—M­— Research Report 2017 Facts Life Science 18 19 The idea wasThe standardized structures and and ­structures fit on asingle to create a the market,the and at the sametime diversity of could effectively compounds that of ­collection of mostdrugs on represent the represent the microtiter plate. molecular targets may be adopted by the community. ­compounds develop and to assays screening is ­ Kubicek’s team screen, of this combinatorial the –considering the results at CLOUD CeMM ­applications made were for with approved drugs onA number new potential of discoveries the library. CLOUD the reductionist concept­validated underlying phenprocoumon Thereby they synergize. and representing flutamide the clusters from able show to alldrugs that and actually were went back the to entire approved list, drug the scientists by thisfinding, Encouraged cells. combination cell induced death inthose massive –and The treat hitthe to behard to eye. bull’s combination cells known cancer on drug prostate the the tried scientists Hence, cancer. prostate but alsointhe development and progression of develop inthe normal factor transcription a crucial –anuclear interaction as protein acts that drug synergistic of the observed target molecular as identifiedThe team the androgenreceptor (AR) thekilled leukemia cells. efficiently PPC In combination, and flutamide ananti-thrombosis compound.coumon (PPC), the treatment and cancer, of phenpro prostate approved adrug for flutamide, action between the ­ ­ ­plasma on relevant the maximum clinically based The dose for compound each determined was experiments. cell line well-suited for drug of acancer leukemia KBM7 cells, on the viability combinations of­pairwise compounds CLOUD Kubicek’s of group the investigated effect time put to the the to CLOUD It was test: confident the that isthe CLOUD setideal of scientists foundscientists astrong synergistic inter concentration. With this procedure, thisprocedure, concentration. With ­ment and of maintenance the prostate, ­ - Fund (FWF) supportedthisstudy. and Development and the Austrian Science the National Foundation for Research, Technology, Federal Ministry of Science, Research and Economy, A Marie Curie Career Integration Grant, the Austrian Funding May 22, 2017. DOI:10.1038/nchembio.2382 the ­ of the CLOUD uncovers a synergy targeting Bennett KL &Kubicek S. A combinatorial screen Ivanov V, Colinge J, Bock C, Kratochwill K,Menche J, Boidol B, Dürnberger G,Folkvaljon Y, Stattin P, ­Caldera M, Wagner A, HerzogR,Penz T, Schuster M, Lardeau CH, SdelciS,Schirghuber E,Müller AC, Licciardello MP, Ringler A, MarktP, KlepschF, References androgen receptor. NatureBiology, Chemical

Flutamide+PPC PPC Flutamide DMSO unknown target 34 drugs with AR

STEAM 26,800 FDA-approved products + 2,171 active ingredients β-tubulin small molecules 954 SysTEmic 1,415 unique with known Clustering 920 drugs Molecules unique CLOUD target drugs smAll 239 +

STEAM Merge 35 active forms of prodrugs low FIRE intensity

high

DAPI AR_FIRE DAPI AR_FIRE DAPI AR_FIRE DAPI AR_FIRE Biology et al., Adapted fromLicciardello the 308 CLOUD drugs. procedure leadingto filtering andclustering ­representation of the Fig. 2 Biology et al., Adapted fromLicciardello for 24 h. Scale bar 20 µM. the combination of both flutamide, 35 µMPPC or cells treated with 15 mM analysis of prostate cancer Fig. 1 Immunofluorescence Nature Chemical Nature Chemical Schematic 2017. 2017.

Ce — M­—M­— Research Report 2017 Facts Life Science 20 21 Chemical Biology Vladimer et al., modulation. Adapted from for visualizing immuno­ pharmacoscopy principle ­representation of the Fig. 3 Schematic 1 Nature 2017. Isolate mononuclear cells Drugs pre-transferred toplates M O G N H D C K E B P A F L J I 1 234567891011 12131415161718192021222324 from donor M O G N H D C K E B P A F L J I 1 234567891011 12131415161718192021222324 Killer cells Natural B cells T cells Dendritic cells Macrophages possibilities for drug discovery. fornew drug possibilities new into insight immune cell and interactions thereby enables allows of Vienna, developed University and the at CeMM Medical Pharmacoscopy,and their amicroscopy orchestrate actions. method highly complex communicate to pathways biochemical signaling immune of awide mannerdesired ischallenging: cells range use influence that the immune ina system for The search new drugs A Microscopefor DrugDiscovery M O G N H D C K E B P A F L J I 2 1 234567891011 12131415161718192021222324 M O G N H D C K E B P A F L J I 1 234567891011 12131415161718192021222324 Incubate with drugs 3 4 labeled antibodies Fix and stain with Automated microscopy DMSO Pos. ctrl

Drug y Drug x 5 Contacts of ~20e3cells per image measured interaction score Ex-vivo spatial

cut xel offf Pi potential immunological Low potential immunological High B cell A cell and accuracy. of immune cells withinblood speed withhigh interactions and direct patterning spatial overall the designed quantify to algorithms ­analysis iscombined analysis with image single-cell high-throughput fluorescent microscope with ments: with pharmacoscopy, astate-of-the-art microscopy method meets that those require published a Giulio Superti-Furga Director agroupIn 2017, led of by at CeMM scientists contact. ­cell-cell for monitoring inparticular drug, ulatory of apotential the immunomod effect measure to and robust ­ of alack been fast there has monitor. to sensitivity Until recently,extreme resolution high very and requires that contacts soluble by cell-cell interaction proteins and direct consists of Itoften acombinationits nuances. of immune issubtle inall signaling and track to hard as ­influence on thedifficult, immune is system or molecules small biologicals aspecific take that immunotherapies.cancer However, find to aconcept in put use to or cell types, structures the specific immune against response direct to for drugs modern targets exploited molecular as cellular communicationThese be can pathways ­soluble cell-cell contacts. proteins or direct by activated pathways, biochemical signaling immune of awide cells range use purpose, that sophisticated requires communication.that For coordination is necessary fine-tuned ­system, smooth and controlled of this functioning To cells. and remove damaged stasis the ensure immunekinds, cells also monitor homeo tissue pathogens of invading all only against protect to not Itserves ofnetwork tasks. withabroad range biological complex, yet vastly highly organized ­biochemical –the reactions immune isa system and molecules countless signaling different many hundred cell types, of different Dozens technology technology - - - ­supported this study. and the ­ the ­ the Knut and Alice Wallenberg Foundation, ­Development, theSwedish Cancer Society, ­Foundation for Research, Technology and ­Science, Research and Economy, theNational Organization, the Austrian Federal Ministry of Foundation, theEuropeanMolecular Biological ­Science Fund (FWF),theSwiss National Science The EuropeanResearch Council, the Austrian Funding Biology, April 24, 2016. DOI:10.1038/nchembio.2360 ulatory potential of common drugs. ­Superti-Furga G.Globalsurvey of theimmunomod Knöbl P, Kubicek S,Helleday T, Jäger U and ­Warpman Berglund U, Sabler M, Lopez de la Fuente O, Huber KVM, Lardeau CH, Sanjiv K,Ringler A, Vladimer GI,Snijder B, Krall N,Bigenzahn JW, References ­medicine. for the development precision of personalized –amilestone drugs their various to response applied patient individual test to samples for could pharmacoscopy be that, Above system. ofon molecules the signaling immuneeffects theimplemented by visualizing research inbasic alsobe itcan discovery, tool for drug powerful provides pharmacoscopy throughput, not only a immune at resolution high system and high amethod theBeing modulation track to of the their killing. by T-cells is recognized that and to leads aprotein cells, complex of cancer on the surface induces the upregulationCrizotinib of MHC immunomodulatory potential. ­uncharacterized cellsmall ­ lung anFDA-approved forcrizotinib, non- drug completely identified The scientists unknown. been had such aneffect for many of these drugs, and, percent often tested allthe approved drugs immune ­ found among interactions that cells of the They results. astonishing producing ­activity, forsearch compounds withimmunomodulatory ­ Chemical for Kubicek’s Austria PLACEBO (Platform and Stefan of Vienna University ­Medical withthe collaborated team ­Superti-Furga’s put to their new methodEager the to test, Torsten and Ragnar Söderberg Foundation Marie-Skłodowska-Curie Fellowships system were affected insome by way affected were system Biology) laboratory at CeMM to to at CeMM Biology) laboratory cancer, as havingapreviously as cancer, Nature ­Chemical -

Ce — M­—M­— Research Report 2017 Facts Life Science 22 23 Bloody Lady

+ Diagnosis Becomes Personal + New Hope for a Rare Malignancy + Natural Antibodies Reveal their Impact + The Search for Healing Mutations Life

Bloody Lady: Well, I don’t know much about DNA, as I got rid of mine a long time ago. Miss DNA: Ehm… excuse me!? Bloody Lady: Yes, what’s wrong with you? Facts Miss DNA: Got rid of me? Bloody Lady: Yes! I kicked you out! Miss DNA: I left YOU!! Bloody Lady: Oh, please!! ­Anyway… as I was saying. Wait… what was I saying? Oh yeah! Have you heard about single-cell-resolution?­ They’re looking at cells ­individually. Under a microscope. and traffic system. affecting bloodcells, allof their components therapies and improvethediagnosisof diseases at CeMM toinvestigate thecauses, find new research from many different angles is from hematopoiesis. Therefore, a large amount of many rare diseases also affect thecellsderiving prevalent death causes worldwide. Beyondthat, Cardiovascular diseases are amongst themost an uncertain outcome and oftenshortenedlife. threat that leavesthemajority of patients facing during thepastdecades, still a major health ­malignancies are, despiteremarkable progress the origin of many diseases. Hematological At thesametime, thecirculatory systemis maintain tissuehomeostasis and systemintegrity. builds an overarching surveillancemachinery to potentially damagingforeignbodies–butit also and protectsfromintrudingpathogens and other A whole army of immunecellspatrols the vessels besides thetransportation of gases and nutrients. cells, bloodservesnumerousother functions However, consistingof amazing great variety of through our body relentlessly with every breath. task of theredjuicethat our heartpumps oxygen toevery lastcellof theorganism – a vital stream. Packed with hemoglobin,they deliver are the mostcommontypeof cellsintheblood DNA-free erythrocytes, aka redbloodcells, ­performed

Patients on themake a therapy cancer work, itseffect cells withthe most To prevalent mutations. only work cancer against drugs In many cases, response. mutationsimpact on of drug the various cells of and cancer the heterogeneity high diverse treatment due the to the right predict to is hard it genetic analyses, Even withstate-of-the-art physician. ­attending therapy for isabig challenge an effective the ­ make them work.thisstage, At treatment options little to time left and very onlyand have often relapsed few blood cancers refractory from suffering Patients ­treatment. provide to they acurative fail in many cases for blood in use are therapy –­ cancer Today, more ahundred than agents individual compoundsdifferent or compound ­ by need beaddressed to theyTherefore, often of inthe course the accumulate disease. often of by mutations abroad range that be caused can leukemia like malignancies Haematological blood insmall samples. therapies bydrugs testing personalized couldpharmacoscopy beagroundbreaking new method improve to For blood cancers, medicine. precision the need for personalized find to ithard makes appropriateoften treatments andemphasizes that Afact patients. the affected as diverse as isadisease Cancer Diagnosis BecomesPersonal 18 16 14 10 12 8 6 4 0 2 Most recent regimen (4/17) p =0·0013 identifying identifying combinations. however, Pharmacoscopy-guided treatment (15/17) interpret drug action. drug ­interpret to used bequantified and can phenotypes never-beforeand other algorithms, visualized developed methods, machine analysis learning ­combination specially withpharmacoscopy’s ­ kill those selectively healthy that including from cells, possible ­ to ­ great content microscopy. automated confocal The high-throughputusing andthen­ high- quantified on cells the are individual of drug each effects The patients. individual samples from collected options­hundreds of liquid insmall drug biopsy The method pre-test allows quickly to tool. 22/23),proved page (see beapowerful to of Vienna University of the Medical ­clinicians by efficacy for and tested at CeMM itsclinical a microscopy method developed by scientists given ­ single cell of a on every cells must beobserved cancer cells, leaving the rest unaffected. In leaving the unaffected. cells, rest cancer advantage of itis isthat pharmacoscopy advantage sample. For this purpose, pharmacoscopy,sample. Forthispurpose,

No response Response distinguish drugs that affect all cells, allcells, affect that drugs distinguish disease Progressive disease Stable response Partial remission Complete

­Haematology ­Vladimer et al., Adapted fromSnijder and paired binomial data. by McNemar’s testfor p value was calculated logical malignancies. with aggressive haemato treatments for 17patients pharmacoscopy-guided recent regimen and of response with themost ­Comparison of overall guided treatment. with pharmacoscopy- progression-free survival Fig. 4 Overall response and 2017. The Lancet

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Ce — M­—M­— Research Report 2017 Facts Life Science 26 27 Complete remission Haematology Vladimer et al., Adapted fromSnijder and first-line treatment. ­leukaemia taken before with acute myeloid samples of 20patients biobanked bonemarrow spective analysis using ­overview of theretro­ therapy. Schematic acute myeloidleukaemia and response to first-line Fig. 5 Non-responders (ten patients) (ten patients) Pharmacoscopy 2017. The Lancet aspirates from20patients with acute myeloidleukaemia taken

Biobanked bonemarrow at timeof diagnosis address yet address to more diseases. couldand that precision bedeveloped further gives unprecedented resolution material ­primary the ­ patients, but alsoearlier in only for late-stage not use, to drugs prioritize doctors how medical could pharmacoscopy change In the future, intervention quickly. must beselected at the time of relapse whereespecially anew the patient during treatment beused process, can and that reliable test predictive fast, is arobust, provide results These evidence thismethod that withor withoutunachievable, genetic assays. the of prediction treatment outcome been has in such accuracy Inthe past, in 90%accuracy. resulted that withpharmacoscopy study spective aretro performed and MedUniCeMM Vienna ofleukemia (AML),the from scientists team newly-­ and responding non-responding stratify to of the methodTo the ability determine specifically Superti-Furga. Giulio Director by Scientific of the CeMM team and accompanied of Vienna University Medical Lymphatic and T-cell Leukemia Lymphoma of the for Lymphoma, Director Program Staber, Chronic isled The by ongoing Philip study ment. clinical weeks compared line of their to treat last 22.6 weeks 5.7 to from guided therapy increased inaccordance withpharmacoscopy- treated were of patients who survival progression-free median the Inaddition, treatments. ­previous respective responded(4 out well similarly of their to 17) or complete partial while only remission, 23.5% copy-monitored therapies achieved personalized who out (15 pharmacos of received 17) ­recruited of patients the cancer showedstudy 88.2% that analysis clinical of a interim afirst, In 2017, process. It’s single-cell functional analysis of analysis functional single-cell It’s process. diagnosed patients with acute myeloid patients withacute diagnosed Cytarabine, etoposide, and daunorubicin quadruplicate 18 h incubation. 125 drugcombinations in 40 ×384 well plates Brightfield CD34+CD117+ DAPI

- 15,360 images per patient - Automated microscopy - and image analysis (EMBO) supportedthisstudy. and theEuropeanMolecular Biology Organization Foundation, theSwiss National ScienceFoundation Technology and Development,theMPNResearch and Economy, the National Foundation for Research, the Austrian Federal Ministry of Science, Research Science Fund (FWF),the Austrian National Bank, The EuropeanResearch Council (ERC),the Austrian Funding DOI: 10.1016/S2352-3026(17)30208-9. pilot study. TheLancetHaematology ­interim resultsfrom a single-arm,open-label, with aggressive haematological malignancies: ­Image-based ex-vivo drugscreeningfor patients and ­ Valent P, Kubicek S, Jäger U, Staber PB Kenner L,Sperr WR, Kralovics R,Gisslinger H, ­Felberbauer F, Müllauer L,Prager GW, Korkmaz B, ­Mayerhöfer M,Simonitsch-KluppI,Ocko K, Prutsch N,Merkel O,Ringler A; Jeryczynski G, Gültekin S,Kazianka L,Bigenzahn J, Hörmann G, Lopez de la Fuente O, Choi HS; van der Kouwe E; ­Schmolke AS, Kornauth C, Sabler M, Snijder B*, Vladimer GI*,Krall N,Miura K, References Superti-Furga G(*equalcontribution).

On target Quantify celldeath basedon nuclear morphology Inactive , Nov 13, 2017. Toxic rare type of cancer cell. of cancer type this rare against and effective compound identifiedas highly specific was anew platform, screening high-throughput drug CeMM’s With missing. been hitherto therapy has aneffective blood cancers, T-cell prolymphocytic leukemia (T-PLL) isone of the most ­ New Hopefor a Rare Malignancy examined cells. the examined withthe screen biological of the setup drug of the samples, same the of linking results cells with performed expressionwas profiling Biology). Simultaneously,for Chemical protein Austria PLACEBO platform (Platform screening high-contentCeMM’s and high-throughput drug compounds different them 106 exposed to in and lymph node samples 86patients from and bone marrow, blood fresh of used scientists Boidol. The team Bernd student Ph.D. by CeMM and first-authored of Vienna, University ­Medical ­ hemato- Kubicek and Stefan led by CeMM-PI study overcome inacollaborative was obstacle This their therapy. improve to studies clinical perform to hard it was of leukemia, form withthisrare diagnosed are patients few year per only and very as available, treatmentfar,curative there is So no ­infiltrates. spleen and the lymph skin well nodes as as symptoms enlargement of including the liver, exponentially systemic proliferate and cause theentire cells the infiltrate organism, cancer withinashort­progression time, of T-PLL isfast: the by chromosomal­Triggered aberrations, of leukemia. one types of the most aggressive of the are T-PLL, origin potential dangers, the body protect to from built Tcells, Mature oncologist the from Philipp Staber put the potential of venetoclax the to test. and these positiveresults confirm to performed be will study clinical aninternational In 2018, T-PLL therapy. for future ­promising candidate ofscreen the a patient samples, the makes drug ­combined withthe outcome of the ex-vivo human of test venetoclax inT-PLL patients, ofT-cell results thisfirst-ever The striking count. of their symptomsdecrease and drop of their anyto in afast resulting other treatment, T-PLL patients who not had previously responded twolate-stage givento was venetoclax ­profiles, and protein expression on these drug Based venetoclax. to explaining their sensitivity BLC-2, thethat T-PLL cells show expression ahigh of profile of the analyses patientsamples confirmed The expressionand cells. selectively tumor kills roleplays acentral inthe regulation of apoptosis which inhibits BLC-2, aproteintoclax called ­treatment of chronic lymphatic Vene leukemia. a compound only recently approved for the cells showed venetoclax, to response adramatic the asuccess: T-PLL was setup experimental This malignant malignant -

Ce — M­—M­— Research Report 2017 Facts Life Science 28 29 Boidol et al., ­profiling. Adaptedfrom ex-vivo drug-response ­profiling via TMAs and and used for expression consenting patients biopsies were taken from Lymph node and liquid with BCL-2 expression. samples and iscorrelated vivo responsein T-PLL strongest differentialex Fig. 6 Consenting patient Venetoclax shows Blood 2017. biopsy node Lymph biopsy Liquid or blood-2017-05-785683 ­leukemia. ­BCL-2 inhibitor venetoclax in T-cell prolymphocytic and Staber PB. First-in-human responseof Moriggl R,Merkel O,Kenner L, Jäger U, Kubicek S ­Hilgarth B, Sperr WR, Valent P, Simonitsch-KluppI, Hopfinger G,Hauswirth A, Panny M, AretinMB, Kazianka L,GültekinS,HoermannG,­ Boidol B, Kornauth C, van der Kouwe E,PrutschN, References Blood, Sep27, 2017. DOI10.1182/ suspension Single-cell Tissue microarray Mayerhoefer ME, Mayerhoefer ME, Conditional screening 4 concentrations 106 compounds triplicates supported thisstudy. and Development and the Austrian National Bank the National Foundation for Research, Technology ­Federal Ministry of Science, Research and Economy, The Austrian ScienceFund (FWF),the Austrian Funding

profiling expression Protein Ex-vivo drug-response

profiling atherosclerotic plaques. of area cells and neutrophils inthe perivascular mast numbersof activated increased exhibited mice the sIgM-deficient with such a response, Consistent reactions. inflammatory powerful the most andreactions iscapable of triggering role­significant inthe development of allergic of antibody plays that another a type of IgE, inthe amountstion, production resulting of vast the genera of lack impaired to sIgMleads B-cell atherosclerosis development. They found that mice showedthese sIgM-deficient accelerated authorlead why study ina first –investigated Tsiantoulas –withDimitrios as the researchers model system, anexperimental sIgMas ­lacking miceUsing genetically modified completely ofunderstood action mechanisms these antibodies. poorly on hitherto details intriguing elucidated of Vienna, University of theDiagnostics Medical Laboratory the Division of Medical-Chemical group Binder’s together at with CeMM Christoph by in2017 Twothemselves. performed studies, regulation and development of Blymphocytes the also play antibodies role animportant inthe pathogens, against agents protective of sIgMas roleHowever, the studied extensively from aside invasions. and blocking ­ structure their pentameric strong inter building an antigen, appearto ­ inthe initial to response the are the first induction SIgM of Tcells. cognate they don’t antibodies, need known “natural” as – of life produced B1cells by inearly innate stages Amajor of the sIgMare part found invertebrates. immunoglobulin the(sIgM) are largest isotypes IgM secreted afive-pointed like star, Shaped homeostasis. on B-cell about the effects far-reaching antibody’s details intriguing expandedrevealing and intensified, further was on IgMs atherosclerosisto research and In2017, liver inflammation. walls that leads chronic inflammationvascular of life-threatening work the IgMantibodies on against ­Binder how reported natural year, Christoph only the that group last ledIt was by CeMM-PI Reveal their Impact NaturalAntibodies ­actions with exposure to to exposure microbial -

ahpyilgcl implications. ­pathophysiological mayhave broader these findings such mice, accelerating atherosclerosis in IgE, plasma miceto robustly increased lead sIgM-deficient in functions impaired that B-cell Considering completelya hitherto of unknown sIgM. function – regulator of negative signaling BCR as itacts as development, proper B-cell sIgMfacilitates that indicates insplenic­signaling The data B2cells. development, as it induces increased BCR ­development, BCR itinduces increased as of sIgM isresponsible for B-cell abnormal demonstrated the results that These absence reversed. deficient mice was ­ B-cell When the ­ (pBtk). kinase tyrosine Brutin’s including other ­ levels of increased to leading receptor (BCR), accompanied B-cell by active anabnormally in the ­ numbers zonein the and marginal decreased B2-cell development. accumulation Their unusual splenic abnormal experience sIgM antibodies Tsiantoulas, why investigated mice lacking A second study, alsofirst-authored by Dimitrios the immune system. ­treatment options the of balance by restoring thisknowledge could open up new In future, atherosclerosis. against IgMprotect natural potential by which mechanisms levels high of in immune ­ ­completely new ­ a revealed theBeyond experiment that, and itsinhibition that prevents the damage. provoke in can vessels reactions inflammatory shown IgE was that it time, Forthe first effect. the reversed ­anti-IgE –which antibodies fully the the fed scientists mice withneutralizing acceleration, atherosclerotic disease observed To prove IgEisindeed that responsible for the receptors downstream of BCR signaling, downstream ofreceptors signaling, BCR follicles out of be to the spleen turned development inthe spleen­ of sIgM- scientists inhibited pBtk, altered altered inhibited pBtk, scientists regulation, extending beyond the extending regulation, function of sIgMantibodies function

Ce — M­—M­— Research Report 2017 Facts Life Science 30 31 Research et al., Adapted from Tsiantoula aortic root lesions(×50). eosin-stained (H&E) crographs of hematoxylin- ­Representative photomi Ldlr ­atherosclerosis in reverses accelerated Fig. 8 Scientific Reports from Tsiantoula et al., bars) mice. and sIgM sIgM and NF(black)cellsof B cells(red), T1 (green) MZ (grey), CD21 numbers of FO/T2 (blue), graphs show absolute ­cytometry plots and bar ­Representative flow B cell development. results in altered splenic Fig. 7 −/− +/+ SIgMdeficiency IgEneutralization Circulation sIgM (light-colored bars) −/− 2016. −/− (dark-colored ­Adapted mice. + CD23 2017.

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CD21 2017. DOI:10.1038/s41598-017-03688-8 development. ­signaling that resultsin abnormal splenic B-cell Secreted IgMdeficiency leadstoincreasedBCR ­Bergthaler A, Mallat Z, Jumaa H and Binder CJ. 2) Tsiantoulas D, KissM,Bartolini-Gritti B, DOI: 10.1161/CIRCRESAHA.116.309606 Circulation Research ­Accelerate Atherosclerosis inSecretedIgMDeficiency. ­Mallat Z and Binder CJ. IncreasedPlasmaIgE Perkmann T, HartvigsenK, Conrad DH,Kuiper J, 1) Tsiantoulas D, BotI,Ozsvar-Kozma M,GöderleL, References 10¹ 10² 10³ 10⁴ 10⁰ 10⁰ CD23 10¹ Scientific Reports 7:3540, June 14, Ldlr Ctrl -/- 10² , November 30, 2016. 10³ sIgM +/+ 10⁴ 10⁰ 10¹ Ctrl 10² Fund (SFB F54) and theEuropeanUnion. 2) This work was supportedby the Austrian Science Heart Foundation supportedthisstudy. the EuropeanResearch Council (ERC) and theDutch 1) The Austrian ScienceFund, theEuropeanUnion, Funding 10³ sIgM Ldlr -/- -/- 10⁴ slgM

-/- (cells x10⁶) 48 54 36 42 30 10 0 5

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T1 SIgM SIgM-/- CD23 CD21 SIgM+/+ -/- + - SIgM FO/T2 SIgM+/+ SIgM-/- +/+ MZ SIgM Aortic root lesion area -/- (10⁴ μm²) SIgM Velimezi as co-lead authors, Loizou’s team team Velimezi authors, Loizou’s co-lead as The many billions of nucleotides strung are that whole arsenal of molecular machineries stand by stand whole of machineries molecular arsenal were ablewere cell showed lines that create to aknock- Fanconi anemia (FA): this rare genetic­Fanconi anemia(FA): disorder thisrare diseases serious fail, If those mechanisms repair Ph.D. student Martin Moder and postdoc Georgia Martin student Ph.D. inthe apathway In order cell’s identify to under constant bombardment. Reactive moleunder Reactive bombardment. constant nucleus-containing cell of­nucleus-containing the body. a Hence, occurs replication damage DNA –DNA faulty from their chromosome fragility and isworsened their chromosomefrom fragility myeloid The high leukemia and solid tumors. by mutations ofis caused genesinvolved in addition to the already disrupted FA genes. FAin addition genes. the to disrupted already the scientists mutagenesis, and insertional library and maintain of damage forms various repair to oftens thousands of inevery day times per together inthe chromosomes of the cells are together with international collaborators, chose collaborators, together withinternational group at CeMM, the of research Loizou Joanna the ­ biochemistry that could remedy this defect, could that ­biochemistry remedy thisdefect, the to crosslinking by their hypersensitivity the elucidation of the disease. potential contributions of important thisprinciple while making to proved the researchers CeMM hematologicalcells of disease, arare Tested remedythat the impact of gene another, defect. with fatal DNA mutations finding concept: isabrand-new Synthetic viability The Searchfor HealingMutations agents ofagents chemotherapeutic treatment. seemingly unusual approach. In a study with approach. Inastudy a seemingly unusual after the other, incellsafter withthe Fanconi anemia out for nearly allnon-essential human genes, can result. One example for such a disease is example One for such adisease result. can cellular function. cules of the cellular metabolism, mutagenic of mutagenic the cellular metabolism, cules crosslink damage. The effects of the progressive The effects damage. crosslink combination with a CRISPR-Cas9 inactivating inactivating ­combination withaCRISPR-Cas9 substances that are consumed, sunlight or consumed,sunlight are that simply­substances susceptibility of FA patients derives cancer to susceptibility systematically disrupted every single gene, one single gene, every disrupted ­systematically defects, complete bone marrow failure, acute acute completedefects, failure, bone marrow congenital including devastating, are disease defect. By using human By haploid using celldefect. lines in cellular proteins that repair DNA interstrand interstrand cellular proteins DNA repair that - “synthetic viability”. The rationale behind this “synthetic viability”. This workThis demonstrated genome-wide that This study was supportedby theEuropean Schischlik F, Slavkovsky R,Kralovics R,Schuster M, ­Wiedner M,Ferreira daSilva J, Robinson-Garcia L, DNA damage repair mechanisms. Beyond that, Beyond that, mechanisms. repair damage DNA screens identify synthetic viable interactions 3 the Austrian ­ (*equal contribution).Parallel genome-wide is less detrimental for cells than a deficiency of for cells adeficiency detrimental than is less inidentifying effective are screens CRISPR/Cas9 leading to DNA repair disorders. disorders. repair DNA to leading into mechanisms human cell biology and disease key insights identify to effort Loizou’s in Joanna found what they looking were upon for: loss of the Fanconi only anemiapathway –animportant clearly showedthis study the that loss of both of cells withdefective the survival increase that throughput for scoured assay, the researchers ahigh- With cells. shouldthat the diseased kill Bock C, Ideker T, Jackson SP, Menche J and Loizou JI Moder M*, Velimezi G*,OwusuM,Mazouzi A, ­Molecular Biology Organization (EMBO) and DOI: 10.1038/s41467-017-01439-x. Subsequently, crosslink interstrand DNA anemia. functional BLM helicase complex, BLMhelicase cellular a functional References Funding between theBLMhelicase complex and Fanconi genetic ­ interaction “synthetically viable” of another gene or pathway. And the scientists contribution the to genetic elucidation of thisrare components (BLMand Fanconi anemia pathway) be suppressed bycan amutation or abrogation concept or agenetic isthat phenotype defect thistreatment after better cells survived that survival of Fanconi anemia cells was increased. of Fanconi anemiacells was ­survival disease. This work This represents yet anotherdisease. chapter the kind damage of DNA generated, was ­damage disrupting additional genes, a process called called aprocess additional genes, ­disrupting Nature Communications, November 1,2017. Science Fund (FWF). partners partners

Ce — M­—M­— Research Report 2017 Facts Life Science 32 33 ­Communications Velimezi et al., Adapted fromModer and ­apoptosis was measured. 48, and 72 h, then treated with MMC for 24, either leftuntreated or induced by ICLs. Cells were ­damageapoptosis and cells alleviates DNA complex in Fig. 10 Communications and Velimezi et al., esis. Adapted fromModer and insertionalmutagen approaches: CRISPRCas9 two parallel genome-wide following MMC exposureby actions for Δ synthetically viable inter identification of genetic FANCC viable interaction for complex as a synthetically screens identify theBLM ­insertional mutagenesis CRISPR-Cas9 and Fig. 9 Genome-wide . Workflow for the Loss of theBLM FANCC FANCC Nature 2017. 2017. -deficient cells Nature ­ - Infection of 100million∆ Infection of 100million∆ HAP1 cells with gene-trap virus HAP1 cells with GeCKO library FANCC FANCC selection Puromycin Percent cells Percent cells 100 100 50 50 0 0 UT UT Viable 24 24 h h ∆ FANCC WT Late apoptosis 48 48 h h 72 h 72 h selection Mitomycin C selection Mitomycin C ₂ ₂ ₃ ₃ ₂ ₂

Percent cells Percent cells Early apoptosis 100 100 50 50 ₃ ₃ 0 0 Sequencing of insertionsites UT UT Sequencing of enrichedgRNAs ∆ 24 24 FANCC∆ h h ∆ BLM BLM 48 48 h h 72 h 72 h by Michel Owusu. DNA damage. Pictures induced ­repairing cells (∆ Fig. 11 Doubledeficient FANCC ∆ BLM

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Ce — M­—M­— Research Report 2017 Facts Life Science 34 35 Monsieur Macrophage: What about immune therapy? I know how to eat cells! I am, and always will be at the center of research. Monsieur And I’m not alone. I’ve got my buddies from the immune ­system, like my good ol’ friend Mr. T … Cell. I pity the fool that under­estimates the immune Macrophage ­system. When we all get together, there’s nothing that can stop us. Cancer: Come on, you don’t + A Momentous Breath even know what I am! + Complement on the Loose Monsieur Macrophage: Not yet … But they do! Life Facts of bowel homeostasis. disease and helpedunderstand thecomplexity These resultsledto a potentialtreatment for the an important partof theinnate immune defense. control of thecomplementsysteminbowel, rare genetic defect was foundto affect theproper from Kaan Boztug’s team: a previously unknown, environment. Another important discovery came of thebody’s mostimportant interfaces with its the development of defensemechanismsfor one born – a hitherto largely unknownchapter in the lungs after the very first breaths of anew their study of theimmunological eventsin In 2017, Sylvia Knapp and her grouppublished is also oneof themainresearch areas at CeMM. ­appearances and broadrange of related diseases body, the immunesystem with itsmanifold Involved inpractically every functionof the optimized componentsof theimmunesystem. a prime examplefor thecomplex yet perfectly marrow like all other white bloodcells, they are just a few functions. Derivingfromthebone regeneration or tissuehomeostasis, tomention immune response, wound healing, muscle crucial for therecruitmentof the adaptive macrophages intheir various forms are also patrol the vessels for somethingtoeliminate: and internalthreats. However, they notonly forefront of thebody’s defense against external bulky, yet versatile and flexiblecells are at the and digested by macrophages. The voracious, identify itself as healthy and “self” isengulfed substances –everythingthat doesnot clearly Cellular debris, microbes, cancer cellsor foreign - these intruders. from ­biochemical defend to agents the organism equipped of powerful withabroad range immune cells, of highly specialized own arsenal the body, entering from harbor their the lungs microbes To and pollutants. prevent them daily,lungs and withitcome countless airborne adult through of pass airto liters 10,000 than world. allow breaths Around more 20,000 human the to body isexposed outside that of the one of surfaces The has lung the largest of Vienna. University and the at CeMM Medical elucidated was How the immune of the system withthose copes lung challenges but includes inevitably incoming microbes airborne and pollutants. outside oxygen, provides that change environment. vital Adramatic issuddenly lung a to the newborn’s exposed thebreath, first With A MomentousBreath milieu of themilieu lungs. the shape that lifelongsignals immunological molecular releases breath of a first newborn very how the of Vienna, University with the Medical showed, incollaboration at CeMM, Affairs ofby Medical and Sylvia Director Knapp, PI the helpWith of mouse models, the group led immuneepisode system. first inthe lung’s known onlytheless, about little thisvery was Never birth. immediately after ­established for a ­ immune iscrucial inthe lungs homeostasis To theto organism. abalanced maintain ­ of collateral tions the bear risk always immunedefense as and reac protection, tissue hostHowever, line itisathinred between functioning gas exchange and exchange must be gas functioning damage damage ­ - Saluzzo. Pictures by Simona ­newborn mouselung. ­staining of IL-33 in a Fig. 12 Fluorescent

Ce — M­—M­— Research Report 2017 Facts Life Science 38 39 et al., Addapted fromSaluzzo newborn’s first breath. the consequencesof a of thestudy, summarizing Fig. 13 Cell Reports Graphical abstract 2017. Alveolar epithelialcells Type 2 Expansion of alveoli The first breath Il33 Interleukin-33 TNF CXCL1 ST2 Homeostatic M2-AM S. pneumoniae ILC2 IL-13 Newborn lung alveolar space Immature Mono/AM IL-5

Eosinophils ­countries. inWestern disease of death by aninfectious cause pneumonia isthewhy primary bacterial explains simultaneously exchange of gas function the lung maintains that the mechanism same Inother words: by pneumococci. those caused at the such as time, same infections bacterial to with the outside susceptibility world, increase contact the first achieving quiescence lung after in although crucial mechanisms, described able show to the that was intheir study team Knapp’s but microbes, there isacatch: airborne as encountered daily, such ­environmental triggers excessive inflammationto from reaction in the lungs protect effects ILC2-induced These exchange. and healthycalm proper ensure to gas stay and the incheck that ensure lungs system now M2macrophages cells, keep the immune As specialized M2 phenotype. anti-inflammatory into the reside theythat inthe transform lungs: of macrophages the fate second determines signal This cytokine. another the IL-13 molecule, signal release the ILC2s inthe lungs, arrived Once known about their role homeostasis. inlung butwas little else viruses, or influenza parasites against the indefending lungs crucial are ILC2s into thephoid tissue. lung migrate (ILC2s), cells” lym innate “type-2 of immune so-called cell, kind aspecial signal, Following the IL-33 effects. of molecule withawide asignal range (IL-33), interleukin of the to lead 33 the release cytokine at thebreath birth first ventilationous during forces of the spontane that mechanical revealed The study, authored first Saluzzo, by Simona - - the Wellcome Trust supportedthisstudy. and grants fromtheMedical Research Council and the Vienna Science and Technology Fund (WWTF) The Austrian ScienceFunds (FWF, DK CCHD), Funding February 21,2017. DOI:10.1016/j.celrep.2017.01.071 shape thelungimmuneenvironment. and KnappS.First-breath inducedtype-2 pathways Warszawska JM, Jolin H,MesteriI,McKenzie ANJ Starkl P, Lakovits K,Hladik A, Korosec A, Sharif O, Saluzzo S,Gorki AD, Rana BMJ,MartinsR,Scanlon S, References Cell Reports, To maintain functioning ­functioning gas exchange after birth. immediately and must be in the lungs is immune a ­ ­established a for ­crucial ­homeostasis balanced balanced

Ce — M­—M­— Research Report 2017 Facts Life Science 40 41 the innate immunethe innate system. whichfor isakey the regulator of protein CD55, a stop found codon withinthe gene sequence was able shed to on light mystery: thewas clinical group Boztug’s Kaan genes, ­protein-encoding which identifies all andreads sequencing”, kind of genetic investigation “exome called aspecial With thrive. to concomitant failure chronic malnutrition and infections, recurrent to diarrhea severe from ranging childhood, symptoms since early various from ­suffered and therapeuticattempts­hospitalizations The little girl who undergone had numerous Diseases. and Undiagnosed for Rare Institute of the and Ludwig Director at CeMM Boltzmann PI Adjunct Boztug, ­presented of the to Kaan team withapatient out bethe to case turned This conditions. however, devastating to leads regulation, faulty – isvital reaction inflammatory the control­organism, and of dampening an Totissue. the to damage prevent extensive ­stimuli, itisallbut for benign the surrounding cells or other harmful damaged pathogens, aimsat intruding thisbiochemical barrage While component­soluble, of aninflammation. vascular of the complement inwiththe rush system parts lysozymes and different while antibodies, andmediators, other inflammatory cytokines acomplex ofreleasing enzymes, cocktail immunefull blast, newly cells at fire arrived resident Tissue and becomes obvious. system the inflammation, power of the immuneDuring new into insights –and reveals bowel immunity innate homeostasis. come of anuncontrolled complement of part –animportant system out protein shows the by fatal regulatory amissing iscaused that disease Anewly rare discovered damage. collateral from organism the protect to regulation ofTight the immune iscrucial system Complement ontheLoose of thrombosis. oftation CD55deficiency, accompaniedrisk by a manifes amajor bloodthrough disease plasma, lymphatictinal loss vessels to lead of protein inflamed intes of Inthe course thecells. disease, constant stimulationgut flora’s of the immune by the bowel aggrevated inflammation, which is the to lead observed In combination, these effects inthe signaling gut. molecule anti-inflammatory akey CD55 led production reduced to of IL-10, alsoshown loss of that Itwas signaling. cytokine complement proinflammatory inducing system, the CD55protein impaired proper control of the of absence that The collaborative revealed effort mechanisms. molecular the detailed patients of and 11 address atotal able identify to and together the were scientists team, Lenardo’s group joined up with Boztug’s Kaan CD55 gene. mutations inthe inherited toms who alsocarried sympindex patients clinical exhibiting similar with twofamilies identified otherof Health, National Institutes collaborator at the US-based Coincidently, along-standing Lenardo, Michael investigation. young patient needed molecular more detailed offor the the manifestation complex disease Ricocausal Ardy, student was identified Ph.D. by whether thissingle mutation inthe CD55gene, machinery.degradation Yet, adefinite proof of guided acell’s and to usually dysfunctional are protein thegenetic resulting products blueprint, When astop into codon aprotein’s isinserted ablock they of cause proteinas production. stop codons belong the to most mutations, severe Among the plethora of such genetic alterations, - - - - A B function of the affected gene. of the affected function of the unravels novel biologicaloften aspects the investigation ofthat, single genetic defects therapy.medications for personalized Above of approved for testing the­strategic re-purposing facilitates of mechanisms the molecular study where research, disease of rare ­importance the illustrates perfectly thisdisease Thus, of CD55protein absence. inthe case be effective alsofound­inhibits complement to was activity approved that aclinically drug successful: therapy, a potential targeted andidentify were setout the investigators to disease, of this rare consequences the molecular deciphering After β-tubulin CD55 (F2, F3 and F5)p.Gly37Alafs*24 NC1 1 SP 1 P2.1 (F1 and F7)p.Glu50Alafs*12 P1.1 (F6) c.287-1G>A 2 SCR1 NC2 (F8) p.Thr123Asnfs*5 3 P4.3 SCR2 4 P4.2 5 P4.1 ­Sciences (NIGMS)supportedthisstudy. and theNational Instituteof General Medical TUBITAK, the American Diabetes Association (ADA) of Health(NIH),the Turkish National Grant Agency Academy of Sciences(ÖAW), theNational Institutes The EuropeanResearch Council (ERC),the Austrian Funding NEJMoa1615887 of Medicine ­Enteropathy and Journal England Thrombosis. New CD55 Deficiency, Early-Onset Protein-Losing and Lenardo MJ#(* and #:equalcontribution). Ertem D, Kain R,SariS,Erkan T, SuHC,BoztugK# Ogulur I,Snapper SB, HouwenRHJ,Leavis HL, ­McElwee JJ, Krolo A, Kiykim A, BarisZ,Gulsan M, ­Matthews HF, Pittaluga S, FolioLR, Aksu AU, Tutar E,BarisS,Özcay F, Serwas NK,Zhang Y, ­Dalgic B, Beser ÖF, Morawski AR, Karakoc-Aydiner E, Ozen A*, Comrie WA*, Ardy RC*, Conde CD, References SCR3 6 C

CD55/CD31/DAPI CD55 7 2017; 377:52-61, June 28. DOI:10.1056/ (F4) p.Cys267Ser SCR4 8 Control 9 50um 50um 10 GPI-addition SP Patient 5.2 381 with permission. Medical Society. Reprinted © 2017Massachusetts and Thrombosis, 377:52-61 Protein-Losing Enteropathy ­Deficiency, Early-Onset and Ardy et al., CD55 Medicine New England Journal of control. Adapted from patient and a healthy samples obtained from a staining of duodenalbiopsy immunofluorescence Panel C showsindirect used as a loadingcontrol. β controls and five patients. CD4+ T cellsintwohealthy for CD55 in activated protein immunoblot peptide. Panel B shows a dylinositol and SPsignal denotes glycosylphosphati as F1throughF8. GPI eight families are indicated protein expression. The CD55 leadingtolossof the identifiedmutations in expression. Panel A shows leading tolossof protein Fig. 14 -tubulin staining was Variants in CD55 , Ozen, Comrie

-

Ce — M­—M­— Research Report 2017 Facts Life Science 42 43 Virus

+ The Key to Chronicity + Sensing Lipids

Virus: To be, or not to be… that is the question. Cancer: Yes, and a very good question it is, too! But that’s a topic for another time. Bloody Lady: Yeah, we’re not here to discuss the ­existential crisis of a virus. Virus: But it has to be decided once and for all. I have to know whether I’m alive or not! Life Facts for a better treatment. and ultimately find novel therapeutic avenues of how thestudied viruses cause disease, at CeMM, aims to achieve a better understanding Andreas’ team,incollaboration with colleagues immunology, virology and systemsbiology, with cutting-edge molecular techniquesof Integrating well-defined mouseinfectionmodels on infectious and inflammatory pathogenesis. system and viruses with an organ-centric focus on theinterplay betweenthehostimmune At CeMM, Andreas Bergthaler’s groupis working complex viral lifecycleiscrucial. a detailed molecular understanding of the in common? To tackle theseimportant questions, And what do viral infections and cancer have full recovery and an effectiveimmunememory? viral infectionschronic, while othersresultin a of an organism initsentirety? What makes some the ­ than a few proteins and nucleic acids –change biological entitiesconsistingoftenof littlemore secrets. How can viruses –incredibly small the fast-evolving pathogens stillharbor many some major advances duringthepastdecades, health worldwide. Despiteintense research and theless are among thebiggest threats tohuman ­considered tobe alive or not, viruses never and thus itiscontroversial whether they are Although they lack their ownmetabolism metabolism of whole organs like theliver, or ­ cycle of achronic cycle virus. life haveapproach, shed scientists on light CeMM the mysterious Using anovel largely unknown. experimental was ­processes manipulate to those complex­pathogen manages molecular How the tinyfools the undetected. immune remain to system hides inside their itshost’s gene cells expression rewires and the virus treat: to hard particularly are infections viral Chronic The Key to Chronicity adapted. Pictures by Bojan Vilagos, with cellular proteins. polymerase (inred) ­interactions of theLCMV LCMV infection and the ­illustration of an Fig. 15 Schematic

Ce — M­—M­— Research Report 2017 Facts Life Science 46 47 Vilagos, adapted. in red). Picturesby Bojan interactions highlighted interactomes (shared ­influenza andhepatitis C of LCMV and human Fig. 16 depiction Simplified Influenza LCMV Hepatitis C the viral life cycle. for life the viral out beessential to turned polymerase LCMV some of the proteins withthe found interact to The new method provided insight: valuable polymerases. viral by different is engaged that allowed amapping of the cellular machinery dataset the generated interactomes, polymerase other viruses’ from RNA ­publicly data available Combined with “interactome”. a so-called withthe proteinspolymerase of the host cells – theofthey interactions the determined LCMV Therewith, proteins. viral approach tagging to developed Pathogens, anovel inPLOS this year author first as Khamina publishedof the study Kseniya student withPh.D. The researchers, of human infections. chronic viral ­features some of the key recapitulates with LCMV mainly rodents; however, amouse infection immunotherapy infects development. The virus cancer to key leading principles established inpioneering works alsoused that was LCMV awarded were for itsexploration.Nobel prizes and invirology immunology­system –two model anindispensable as served has LCMV For many decades, interactions. these host-virus ­ mechanism the molecular elucidate to (LCMV) the lymphocytic choriomeningitis virus group used Bergthaler’s Andreas ­Cambridge, Biology of Molecular and the MRC Laboratory of Basel In cooperation withthe University largely elusive. remained cycle life inthe steps viral these crucial needed for of However, replication. the details withcellular proteins alsointeracts ­polymerase compatible the to The cell’s gene expression. the blueprints proteins for make to them viral ittranscribes viruses, inRNA polymerase: viral at thispoint Akey enzyme isthe replicate. to of the cell inorder machinery protein-building genetic –itneeds highjack to information the –aproteincapsid shell the virus’s protecting of the cell membrane and uncoating of the viral penetration cell, the to attachment target After perfectly. events coordinated ­molecular are of aseries invades itshost, When avirus underlying ­Sciences supportedthisstudy. The City of Vienna and the Austrian Academy of Funding DOI: 10.1371/journal.ppat.1006758 virus L protein.PLOS Pathogens ­interacting with thelymphocytic choriomeningitis ­Bergthaler A. Characterization of hostproteins ­Pinschewer DD, BennettKL,Menche J and Májek P, Stukalov A, SaccoR, James LC, ­Vilagos B, SahinM,Kosack L,Bhattacharya A, Khamina K,Lercher A, Caldera M,Schliehe C, References theto development of novel therapies. antiviral Ultimately,their hosts. their goal contribute isto and complex of interactions viruses molecular and theemergence of infections chronic viral of the understanding abetter hopeteam gain to and his Bergthaler Andreas their efforts, With of chronic strategies viruses. infection important their mapping inthe human proteome revealed Furthermore, of polymerase. the LCMV partners prehensive of binding the molecular overview provided ofThe results thisstudy com the first ofwith achronic LCMV. strain controlshowed impaired when virus infected protein the lacking TRIM21 Mice effect. ­antiviral one of thewas proteins found have to astrong response, Iinterferon the type regulate to known TRIM21, the ligase Incontrast, survival. partner, binding allowingimportant for virus identifiedas an was immune processes, signaling which DDX3X, isinvolvedhelicase ininnate Among the found. were RNA others, ­properties, Proteins withboth and antiviral proviral Dec 20, 2017. - viral proteins the cell’s gene to make them transcribes the A key enzyme RNA is the viral expression. to ­compatible polymerase: in in ­polymerase: blueprints for viruses, it it ­viruses,

Ce — M­—M­— Research Report 2017 Facts Life Science 48 49 ies progression. ­disease role in shown anunexpected assume to was on myeloid receptor expressed cells(triggering 2) lipid-sensingrecently discovered protein TREM2 induce to liver (LCMV) the inflammation, virus Using the lymphocytic choriomeningitistis. andmechanisms the role of lipids hepati inviral provided new into insights the intriguing disease Sylvia Bergthaler KnappGawish, and Andreas Riem Kosack, by Lindsay performed A study ­pathology, understood. however, not fully was and howchanges thisinfluences the liver such to blood reacts lipids. How the organism inthe induce host’ssimultaneously changes the pathogens infection, asuccessful establish to while relying on their host’s lipid metabolism (HBV and HCV): ­hepatitis Band Cviruses withthe clear example of­particularly the becomes This the progression of the disease. immune of response their host and thereby ­composition the influencing of lipid species, the alter extracellular many viruses In turn, replication and of budding the virus. cell including entry, at many stages infections alsofound lipids that was play a key role in viral but it ­atherosclerosis and rheumatoid arthritis, metabolic disorders, such as diseases matory ­attention: they have implicated been ininflam the immune particular have received system of The interactions lipids with years. in recent evolvedrole has dramatically incellular functions of their the understanding membrane bilayers, thoughtblocks to be first just building plain of However, while lipids for decades. were studied been The has role cycle of life lipids inthe virus the outcome of the disease. A lipid-sensing found play to protein role was animportant for hepatitis. alsoprovides causing ­metabolism, aniche for viruses of hub The liver, the acentral of immune lipid as system. ­consequences for the and progression the response of the disease the ­ alter the At viruses time, same of the pathogen’s cycle. life lipids play infection, akey role stages aviral at different During Sensing Lipids composition of the withfar-reaching host’s lipid species - - ­Austrian ScienceFund (FWF)supportedthisstudy. The EuropeanResearch Council (ERC) and the Funding DOI:10.1038/s41598-017-10637-y hepatitis. Scientific 7:11289,Reports Sep12,2017. aggravates disease in a modelof LCMV-induced Knapp S and Bergthaler A. The lipid-sensor TREM2 Lakovits K,Bhattacharya A, Schliehe C,MesteriI, Kosack L,GawishR,Lercher A, Vilagos B, Hladik A, References diseases. and infectious into inflammatory the providing novel immune system, insights and of the metabolites regulationchanges of numerous infection-induced other linksbetween to uncover expect theresearchers findings, on liver pathologies. their Based virus-induced which opens up new approaches ameliorating to role hepatitis, ­detrimental of TREM2inviral identified ofThe results this study a novel, the virus. improved of the rodents the clear to ability italso upon infection, the viral liver damage The of lack TREM2not only ameliorateddifferent. entirelyfor the thewas TREM2protein, result the micewith genetically modified missing gene However, when the experiment they repeated withhepatitis. associated liver damage severe mice and led the to expected inwild-type species the lipid composition ofperturbed circulating withLCMV foundThe scientists infection that D Trem2-/- WT AP (U/l) Body weight A Scale Bar =100 800 600 400

200 (% initial) 100 80 90 70 0 1 2 dayspostinfection 2 Days postinfection Days postinfection ns 8 3 μm WT WT 4 5 6 Trem2 Trem2 8 10 -/- * -/- 10 ****

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3+ cells in 10 fields 3 WT 4 400 500 200 300 100 5 0 6 Trem2 WT **** 8 -/- * Trem2 10 **** -/- Scientific Reports from Kosak et al., nucleoprotein. Adapted were stained for LCMV WT and Liver sections from infected compared to WT mice: improved virus clearance Fig. 18 Reports Kosak et al., per group). Adapted from was quantified(n = 4mice of positivecellsin10 fields caspase 3 and the number were stained for cleaved of Trem2 sections of infected WT and pathologically scoredliver and bilirubin,(F)histo alkaline phosphatase (AP) (D, E)serumlevelsof ­aminotransferase (AST), (ALT) and aspartate alanine aminotransferase (B, C) serumkineticsof LCMV ­ (A) body weight after LCMV-induced hepatitis: are protected against Fig. 17 netd T and WT ­infected infection, −/−

2017. Trem2 Trem2 Trem2 , (G)liver sections Scientific −/− −/− −/−

mice miceshow mice 2017.

Trem2 -

−/−

Ce — M­—M­— Research Report 2017 Facts Life Science 50 51 Miss DNA

+ Bring in the CROP + A Pattern of Activity

Miss DNA: At the center of many diseases, there is me. Keeping me sane and my integrity whole, is probably the most important task for any body. Luckily for me, I know that CeMM will continue their research into genomics on Life how to keep me pristine. Virus: Oh, come now! Miss DNA: I beg your pardon? Monsieur Macrophage: Pristine? You? There’s … stuff hanging all over you.

Bloody Lady: Yeah, you are Facts ­pretty covered in epigenetics. be involvedinmany diseases. known as enhancers– a process that could also by tissue-specific regulatory DNA elements show that differential allele activity isregulated in 2017. For the first time, scientists were ableto on the patternof active allelesindifferenttissues group ledby DeniseBarlow ­ become popular in academia and industry. The in functional and regulatory biology and has cell sequencing. Itfacilitates highthroughput CRISPR-mediated cellperturbations with single- introduced “CROP-seq”, a method that combines renowned expertinepigenomic technologies, group led by CeMM PI Christoph Bock, a world-­ lized and precisionmedicine. In2017, the a crucial research area inthecontextof persona new ways of manipulation, makingepigenetics insights intoepigenetic mechanisms and offer advances offer unprecedented and fascinating but also onepigenomics. Recent technological CeMM has a strongfocusnotonly ongenomics, but also in many diseases. and ­ crucial roleindevelopment,homeostasis as “epigenetics”, thesemodifications play a activity and accessibility of genes. Summarized large setof chemical modifications can alter the contained inthethread-like chromosomes: a and Gisnottheonly layer of information However, the“hard-coded”sequenceof A, T, C ­functioning of all membersof earth’s biosphere. four nucleotides isthebasisfor theshape and mammals, thesameuniversalcodeof only of life. From thesmallestmicrobestolargest ­organism, theDNA really isthecentral molecule Encoding theblueprintsfor every living adaptability toenvironmental changes – published a study - The interaction between acell’s genetic setup between The interaction However, theof can analysis thisinteraction Genome editing using CRISPR/Cas9 “gene CRISPR/Cas9 using Genome editing number of cells are edited simultaneously using number using simultaneously of cells edited are important for the studied biological forimportant the mechanism. studied are and their guide RNAs selected, mentally –short of pieces RNA guide RNAs CRISPR guide the Cas9 nucleases to cut at a specific at aspecific cut to nucleases guidethat the Cas9 program can lead to a variety of diseases. of diseases. avariety to lead can this program challenging and requires a large number of and alarge be challenging requires an ­ named ­ and ­ ­editing revolutionary tools genome oftwo biomedical research: In anovel combined scientists cell method, CeMM screening Bring inthe CROP steps in the cell’s life cycle –and in discord cycle intheall steps cell’s life for and its epigenetic iscrucial modifications genes. Next, some ofcells experi are the edited Next, genes. genomic thousands of different location –against counted which most determine to genesare scissors” is a powerful tool for biological isapowerful ­scissors” effects. ­system discovery. In pooled CRISPR screens, a large alarge screens, Inpooled­discovery. CRISPR points inorder cell-widedata understand to unprecedented and inunprecedented scale detail. “CROP-seq” enables the study of enables the“CROP-seq” gene study regulation at single-cell RNA sequencing. The new technique sequencing. RNA single-cell - work together to regulate cell state, it was, until until itwas, work cell together state, regulate to Pooled CRISPR/Cas9 screens are most useful most are screens useful Pooled CRISPR/Cas9 In 2017, a team of CeMM scientists led scientists by of CeMM ateam In 2017, they not are well for suited In contrast, studying nologies, succeeded inover team ­ Bock’s which and isboth tedious screen, in anarrayed grow, to recently, and analyze edit necessary Tomechanisms. how understand multiple genes linkedfor acell’s to questions addressing directly the of limitations ­ previously used CRISPR screens. With anelegant design that With screens. ­CRISPR presented Bock amethod­Christoph com that takes advantage of cutting-edge molecular tech molecular of cutting-edge advantage takes chemotherapy. cells against cancer protect that integrating CRISPR genome with editing CRISPR by integrating bines the strengths ofbines pooled the strengths and arrayed ability to grow, to ability for genes example identifying of genes at the same time, studying thousands genes at the studying time, same gene regulation and other complex biological expensive. separately for each CRISPR targeted gene targeted cells for separately CRISPR each single-cell RNA sequencing, they able were to sequencing, RNA ­single-cell determine the gene regulatory impact of many the genedetermine regulatory individual cellsin a experiment. singleindividual methods: coming - - Paul Datlinger. by Christoph Bock & ­transcriptome. Picture and barcode their genome-edited cells ­droplets capture single, Fig. 19 Microfluidic

Ce — M­—M­— Research Report 2017 Facts Life Science 54 55 Nature Methods Datlinger et al., gene. Adapted from gRNAs for thesametarget across cells that express byderived averaging knockout signatures are ­expressed gRNA, and ­together with the cell’s transcriptome RNA-seq toprofileeach ­droplet-based single-cell (C) CROP-seq uses ­physically separated. gRNAs havetobe ­transduced with different profiling, butcells transcriptomeas such ­support complex readouts (B) Arrayed screens on cell frequencies. ­simple readoutsbased which limits themto populations of cells, ­abundance among bulk changes ingRNA (A) Pooled screensdetect ­transcriptome readout. screening with single-cell ­enables pooled CRISPR Fig. 20 CROP-seq

2017.

C Single-cell CRISPR screen with CROP-seq B A Arrayed CRISPR screen Pooled CRISPR screen Multiple gRNAs One gRNA per well gRNA library Barcoded per dish Lentiviral beads ∗ selection Apply Genome-edited pool of cells

Cells

Oil -1 0 1 as readout Cell count as readout Cellular signature mRNA annealing Cell lysisindroplets 1 bead and 1cell Coencapsulation of part of transcriptome gRNA detected as AAAA TTTT AAAA TTTT AAAA TTTT

gRNA1 mRNA mRNA Gene expression Fold change (gRNA vs. control) (gRNA vs. control) grouped by gRNA Single-cell signatures ∗

∗ – droplet sequencing”) (for“CROP-seq” “CRISPR The researchers named their new methodThe researchers The study’s first author, CeMM Ph.D. student student author, first Ph.D. CeMM The study’s Traxler P, Klughammer J, Schuster LC, Kuchler A, January 18, 2017. DOI:10.1038/nmeth.4177 nothing acombination than less ofwas of two Datlinger, created a viral vector that makes makes that vector aviral Datlinger, created Paul single-cell transcriptome readout. ­supported thisstudy. unprecedented detail. Furthermore, with falling withfalling Furthermore, unprecedented detail. Alpar D and Bock C. Pooled CRISPR screening with ­Academy of Sciences and an ERC Starting Grant A New Frontiers Group award of the Austrian in the human Bock’s step, genome. Inanext ­regulation at anunprecedented and in scale of high-throughput analysis gene it permits takes to make a cancer cell in a test tube, they cell tube, inatest make to acancer it takes The outcome cells. in individual of thiseffort throughputcharacterize to sufficient reached ­methods and for sequencing RNA single-cell will use CROP-seq to study the CROP-seq interplay study to use will team genes of of each the 23,000 effects the regulatory the most promising fields genomics. of of thousands ofthe genome effect events editing droplet-based the latest the used scientist visible guideinsingle-cell RNAs the CRISPR Datlinger P, Rendeiro AF, Schmidl C, Krausgruber T, References Funding of genetic inleukemia and epigenetic factors could give rise to the first comprehensive the to could first give rise maps of cells to a less harmful state. cells harmful aless to andrevert to could waysto interfere find new single-cell sequencing costs, this technology thistechnology costs, sequencing single-cell sight: if they succeed in understanding what they succeed inunderstanding if sight: thistool inhand, With experiments. sequencing ­development. have goal The aclear scientists in Nature Methods, ∗

Ce — M­—M­— Research Report 2017 Facts Life Science 56 57 adapted. Picture by Lip Comarella, the mouse allelome. of ­representation Fig. 21 Artistic

The scientists performed acomprehensive performed The scientists authors. co-senior as respectively), Austria, IST and Technology of Science ­Institute Austria, and the Biotechnology,of Molecular IMBA, (now Hudson Pauler at the and Institute Florian and withQuanah University), at Harvard Doc (now post Daniel student Andergassen by Ph.D. group, Barlow’s authored first Denise PI CeMM by withastudy overruled was paradigm This of tissues the organism. the various long benearly to assumed homogeneouswas in whyis one of alleles reason active the pattern of embryonic development.an early stage This while the other one isshut down, ismade inat produce to agene product, betranscribed to is which to one as variants decision of these two The while theallele other issilent. isexpressed, only of one genes, However, afew inthe case into molecule by anRNA the cells. transcribed both alleles and active are Inmost cases, ­disposal. copies of two gene at each its has organism Inmostset of of the genes. resulting itscells, they both contribute their ownnew individual, a to and give rise fuse and egg When the sperm couldthat play a role inpathology. differences tissue-specific allelesall expressed –shows unexpected comprehensive “Allelome” of analysis the so-called of –asurvey However, the of first tissues the organism. the inthe same various “alleles” ismore of those or so-called less thought the that activity the mother, from ­deriving long the other the father. Itwas from oneA cell’s genetic equipment variants, comes always intwo A Pattern of Activity relevant to some diseases of thistissue. be relevant some to diseases X chromosome may that aresult activation, of genesescaping active with over 50% escapers, Most ­ tissues. between dramatically varies ­escapers showed thethe that number researchers of of organs, abroad By range examining tissue. per Xinactivation of genesescaping 10% active of around withanaverage previously thought, mice more are that revealed humans like than However, thisstudy inactivation. humans escape of in X-chromosomal3% genes inmice and 15% only that aroundPreviously, reported itwas somes isshut infemales down. whereinactivation”, one Xchromo of the two chromosome “X some so-called and escaped on the located were Xchromo patterns activity contributed the to genes that tissue-specific influence on the Some allele’s activity. of the allele, but have nevertheless adirect observed an from distance at agreat located often are that regions DNA “enhancers”, on so-called effects due were to of these differences part A large patterns. activity ­tissue-specific alleles contributed the to and observed paternal the maternal between epigenetic differences They found both that geneticmouse tissues. and alleles of the hybrids inacomprehensive setof the (Allelome.PRO) active algorithm catalogue to developed aspecially the used tomes, scientists the transcrip hybrids’ sequencing allele. After or paternal the to beclearlyto maternal assigned sequenced genome, which allowed gene variants withafully mouse strains genetically distinct hybrids of from two obtained were results These ment of many diseases. biological and basic the developstand functions help will new that under insights to unexpected complete provides named, setof alleles was first-ever This alleles. allelome,active as this distribution of showed tissue each aspecific and of and developmental found mice, that stages tissues of allelesanalysis allactive in23different strikingly, muscle showed of rate ahigh - - - - - in the genome outside of the Xchromosome. epigenetic domain co-regulated it the largest overof 10% the extend chromosome,that making of imprinted cluster genes by­surrounded alarge is Barlow by Denise gene in1991, discovered imprinted the first demonstrated Igfr2, that study Interestingly,93 imprinted genesinmice. this of some others provide to agold list of standard the status disputed known genes and clarifying some validating new imprintedof genes, 18 resolves the to discovery these questions, leading study This number of imprinted geneswas. incomplete unclear what the true and itwas of these developmentally geneswas important Previously the specificity tissue orthe sperm. egg by anepigenetic­initiated mark placed ineither allele is that or paternal either the maternal the ­ “genomic imprinting”, complete of picture The newly defined allelome a near-offers ­ 2x forward cross 2x reversecross CAST CAST process that leads to epigenetic silencing of epigenetic to leads that process silencing x x FVB FVB Visceral yolk sac endoderm (VE) pluripotent ESC E3.5 XY Placenta (PI)

XX/XY E9.5 extra-embryonic Liver (Li) MEFs XX XX/XY embryonic XX/XY E12.5 Brain (Br) XX Heart (He) this study. The Austrian ScienceFund FWFsupported Funding 2017. DOI:10.7554/eLife.25125 regulation of allelic expression. Mapping themouse Allelome revealstissue-specific Pauler FM* and HudsonQJ*(*equalcontribution). Theussl HC,Penninger JM, Bock C, Barlow DP*, ­Bammer PC, Muckenhuber M,Mayer D, Kulinski TM, Andergassen D, Dotter CP, Wenzel D, Sigl V, References E16.5 XX XX XX female offspring 3 dayspostnatal Tongue (To) neonatal XX Thymus (vMG) gland Mammary (aTH) (aLu) virgin female Lung eLife, August14, adult XX

Spleen (aSP) Muscle (aLM)

lactating female 3 dayspostnatal gland (lfMG) Mammary Lactating Brain (lfBr) lactation XX · · · · · · · Gene categorisation: · · · · · · · Imprinted: paternal Imprinted: maternal Strain bias:FVB Strain bias: CAST No SNPs Not informative Biallelic RNA sequencing(100bpPE) Ribosomal RNA depletion 23 tissues x 4replicates eLife from Andergassen et al., pooled (XX/XY). Adapted where an entirelitter was indicated embryonic tissues were usedexceptfor of thetissues. Individuals XY (male)indicate thesex categories. XX (female) and different allelic expression classified intooneof seven gene inthe annotation is using Allelome.PRO. Every developmental stages 23 mouse tissues and from RNA-seq data from detecting allelic expression Allelome: Strategy for Fig. 22 ee 2017. Definingthemouse

Ce — M­—M­— Research Report 2017 Facts Life Science 58 59 Cancer Cancer: I’m not just some disease to wage war against! Oh no! I’m much, much more than that! I can mutate, I can hide, and I can do + Bringing Back the Sunshine things that even I don’t know + Unveiled Diversity about. War was declared on me a long, long time ago, even President Nixon declared war on me. And he failed, didn’t he! Yes… you’ll have to try a lot harder than you have been to get rid of me, I have a few more tricks up my sleeve, let me tell you! Miss DNA: Maybe I can help to cure cancer. The better they understand me, the better they understand you. Life Facts medicine for cancer therapy. and realizing thepotentialof personalized in terms of understanding disease variability epigenetics will have an important roletoplay ­heterogeneity. These resultshighlightthat ­characterized by widespread epigenetic ­types afflicting children and young adults, is one of thegenetically mostsimpletumor Institute discoveredthat theEwingsarcoma, at the St. Anna Children’s Cancer Research Christoph Bock’s team,together with scientists a rare genetic disorder that leadstoskincancer. – when activated with a diabetesdrug–can treat mechanism for UV-induced DNA damage which Loizou discovered a hithertounknownrepair progress was made. The groupledby Joanna is ­ research oncancer genomics and epigenomics of cancer therapy. For that reason, a lotof epigenetic mechanismsiscrucialfor every kind Understanding theunderlyinggenetic and radiation approaches obsolete. ­sledgehammer-like chemotherapeutic and new, targeted therapies that may make has beenmadeinthepastdecades, generating and precisetreatment. However, great progress diverse condition,requiringhighly ­ itself tobe an individual, very complex and more than a singledisease. Instead,itrevealed yet tobe attained. Cancer turnedouttobemuch half a century later, this ambitious goal remains disease within thenext25 years. Today, almost the war oncancer, an initiative toeradicate the 1971 when USPresidentRichardNixondeclared It was inhisState of theUnion address in January performed at CeMM and in2017, significant personalized “moon ­ The adjacent, undamaged strand then serves as a as then strand serves undamaged The adjacent, For patients suffering from Xeroderma Xeroderma from For patients suffering Mutations inthe genesfor the nucleotide ­ ­ alife- from ­pigmentosum (XP),the sunturns pathway recognizes the bulky, altered chemically recognizes pathway rough-surfaced growths and eventually skin growths and eventually ­rough-surfaced mechanism that dealswithUV-induced that mechanism DNA –considered (NER)pathway repair bethe to only ligated into the doubleligated helix ligase. by aDNA new complementary sequence iseventually that nucleotides, which are the result of UV damage, nucleotides, which theof are result UVdamage, template a synthesize to for polymerase the DNA DNA repair mechanism. repair DNA unknown of ahitherto which led the to discovery in cell culture, found the alleviate to impact of the was gene defect adrug CeMM, At sunlight. to patients hypersensitive affected making damage, DNA UV-induced repair to impedes the cell’s ability genetic disease A rare Bringing Back theSunshine and removes out them ashort single- by cutting sunlight. The severe disease often leads to to leads often disease The severe of sunlight. giving star into a vicious enemy. into avicious giving star unable Being to cancer upon amounts small even to ­cancer exposure cope with ultraviolet radiation, these so-called these so-called cope withultraviolet radiation, severe conditionsevere The of NER moon children. stranded DNA segment the contains stranded DNA lesion. that death at early age. damage inhuman cells responsible –are damage for the children” develop children” inflammations, heavy excision cells survive UVtreatment a better.­XP cells With survive Xeroderma ­ Xeroderma When the large complexWhen the large proteins of different Abdelghani Mazouzi in 2017, CeMM PI Joanna Joanna PI CeMM in2017, ­Abdelghani Mazouzi Drugs, see page 19/20), they showed 19/20), ace that page see Drugs, damage can no longer be repaired. Accu no longer can berepaired. damage DNA Loizou and her team report on work to away and report her team Loizou first-authoredIn astudy student Ph.D. by using the CLOUD (CeMM Library of Unique Library the (CeMM CLOUD using pathway is mutated and fails, UV-induced and ismutated ­pathway fails, melanoma. Although first described in 1874, 1874, in ­melanoma. Althoughdescribed first more prone basal developing to cutaneous mulating more and more lesions intheir skin tohexamide, a drug used to treat type 2 diabetes, 2diabetes, type treat to used tohexamide, adrug fulfills the sophisticated tasks of thetasks NER the sophisticated fulfills that around the and impaired repair make to DNA treatment. any curative enables XPcells UV-induced repair to DNA cell ­ times XP patientscells, thus more are 1,000 than specially designed chemical screening approach designed screening chemical ­specially damage more efficiently.­damage carcinoma, squamous cell carcinoma, or cell carcinoma, squamous carcinoma, pigmentosum continues lack to - - et al., cell. Adapted fromMazouzi (in blue) within a human damage within thenucleus to sitesof UV-induced DNA green) and MUTYH(inred) DNA repair proteins XPC (in Fig. 23 Molecular Cell Visualization of the 2017.

Ce — M­—M­— Research Report 2017 Facts Life Science 62 63 Cell Mazouzi et al., MUTYH. Adapted from of theDNA glycosylase by antagonizing expression UV-induced DNA damage promotes clearance of Fig. 24 2017. Acetohexamide UV Molecular Acetohexamide ­UV-induced lesions –hence, these findings was MUTYH ­UV-induced damage. DNA repair, butDNA could also pave the for way a ­NER-independent for mechanism removing unknown ahitherto triggering MUTYH, In a series of subsequent experiments, the of subsequent experiments, In aseries ­novel thera of understanding molecular ­fundamental, not previously implicated inthe of removal acetohexamide mechanism: leads molecular the degradation of the DNA repair enzyme theto of enzyme degradation repair the DNA notare contribution only avaluable the to scientists eventually elucidated the underlying elucidated eventually ­scientists debilitating disease of Xeroderma pigmentosum. of Xeroderma disease ­debilitating ­peutic approach for theand severe S NER-independent mechanism Clearance of DNA damage

MUTYH degradation Technology, and Development,theSpanishMinistry The Austrian Academy of Sciences, theEuropean Salud Carlos III-InstitutoNacionaldeBioinformática Wiedner M,OwusuLardeau CH, Ringler A, Weil B, this study. ­Austrian Federal Ministry of Science, Research and Economy, theNational Foundation for Research, Nucleotide ExcisionRepair IsMasked by MUTYH. Repair of UV-Induced DNA Damage Independentof Neesen J, OrozcoM,Kubicek S and Loizou JI. Mazouzi A, Battistini F, Moser SC, Ferreira daSilva J, and theEuropeanResearch Council ERC supported of Science, the Catalan Government,theInstitutode Commission, the Austrian ScienceFund, the Funding References molcel.2017.10.021 Molecular Cell, November 16, 2017. DOI: 10.1016/j. Cell survival ­landscape. by ­ mutations,but isreflected their instead DNA isindeed not the of result diversity clinical They found the that disease’s of Ewing sarcomas. number alarge and Spain examine to Germany France, and Austria, other from scientists in Paris Olivier Curie of Delattre the Institut in Vienna, Institute Research Cancer Children’s Anna St. with Eleni Tomazou of Kovar the and Heinrich up teamed Bock Christoph led PI by CeMM To solve thisapparent the group contradiction, the ­ in differences couldthat explain the observed mutations additional DNA few carry the tumors and development cancer initiating in all tumors, –ispresent fusion –thegenetic EWS-ETS defect bone and adolescents.cancer inchildren Asingle anaggressive for Ewingsarcoma, true ­particularly heterogeneity.­cellular and is This clinical show but still substantial geneticfew defects, exhibit only incontrast, cancers, Childhood tion gene alterations. of accidental the elderly, thishappens mainlyby the accumula ofcontrolled Incancers biochemical pathways. cell needs highly alter complex to and tightly acancer Totissues. those express characteristics, the immune or invasion of system neighboring uncontrolled like properties of evasion growth, have anumber of tumors Malignant characteristic one childhood of cancers. theEwing sarcoma, most aggressive now for investigated been has –aconundrum that highly diverse and they genetically clinically are Nevertheless, mutations. DNA few of the elderly, tumors to only incontrast cancers, Childhood carry Unveiled Diversity widespread heterogeneity inthe epigeneticwidespread heterogeneity disease course among course patients. Ewingsarcoma disease defining Ewing sarcoma as a disease. But disease. as a sarcoma­defining Ewing - with far fewer side fewer effects. with far therapies ­development targeted of personalized, the to becrucial will of heterogeneity tumor and consequences the causes Understanding withlowfor other genetic cancers complexity. also providefindings aninteresting concept The cancer. thisaggressive therapy treat to ized new impulses for the development of personal and the providing therapy response, the disease of epigenetic biomarkers of the course predicting development permitted thus obtained ­sarcoma The new into insights the biology of Ewing state. andness metastatic aggressive withthe tumors’ correlate to appears also Epigenetic outcomes. diversity ­different and ­ the combination of Ewing sarcoma-specific methylationDNA influencesgene activity, may beexplained As by the epigenetic state. among patients Ewingsarcoma observed courses clinical the that diverse suggested results These their cell of origin. methylation DNA of patterns the characteristic of part appear retain to tumors Ewing sarcoma Moreover,patients. found that the researchers between methylationDNA alsovaried patterns and their markedly other from cancers, differ that showedEwing sarcoma unique characteristics of thefacets human epigenome. The examined methylation –one of patterns the most important DNA tumors’ ­Sheffield the to CeMM study at methodsinformatic developed by Nathan For their study, novel the used scientists bio cell-of-origin-specific patterns can lead to can lead patterns cell-of-origin-specific ­ - -

Ce — M­—M­— Research Report 2017 Facts Life Science 64 65 et al., Adapted fromSheffield resistant prostate cancer. ­leukemia; CRPC, castration- chronic lymphocytic CHS, chondrosarcoma; CLL, promyelocytic leukemia; other cancers. APL, acute for referenceprofiles of (PL) fromthisstudy, and cord (UC), and placenta marrow (BM),umbilical MSCs derivedfrombone lines, EwStumors, and separately for EwScell of variation was calculated samples. The coefficient of heterogeneity between per sample as a measure DNA ­ ­samples for median of variation across showing thecoefficient distinct subtypes. Barplot ­heterogeneity without ­inter-individual in EwS showsstrong Fig. 25 methylation levels Nature Medicine DNA methylation 2017. 10 15 0 5 (Coefficient of variation in%) DNA methylation heterogeneity CHS ­January 30, 2017. DOI:10.1038/nm.4273 ­spectrum inEwingsarcoma. DNA methylation heterogeneity defines adisease and Tomazou EM*(*jointly directedthis work). Ambros PF, DelattreO*, Kovar H*,Bock C* ­Ladenstein R,Holter W, de ­ ­Liegl-Atzwanger B, HuppertzB, Leithner A, de Álava E,­ Ambros IM,Hutter C,SorzE, Amaral AT, ­Champigneulle J, Bouvier R, Walder D, Surdez D, ­ Datlinger P, Schönegger A, Schuster M,Hadler J, Sheffield NC,PierronG,Klughammer J, References Pinieux G, Terrier P, ­

Prostate cancerCRPC Guillemot D, LapoubleE,Freneaux P, Schallmoser K, Strunk D, Rinner B, EwS cell line

EwS tumor Laurence V, Michon J, ­Windhager R,DirksenU,

CLL Nature Medicine, MSC (BM)

Normal prostate APL

Glioblastoma

MSC (UC) ­Austrian Academy of Sciencessupportedthisstudy. the Human Frontier ScienceProgram and the kapschgroup), the Austrian ScienceFund (FWF), donation fromKapsch Group(www.kapsch.net/­ The Austrian National Bank (OeNB), a charitable Funding

MSC (PL) Intra-tumor Inter-cancer Inter-individual Levels of heterogeneity Nature Medicine from Sheffieldet al., (­ within EwStumors (inter-individual), and between EwStumors cancer types(inter-cancer), at three levels:between sarcoma (EwS) analyzed ­heterogeneity inEwing ­sarcoma: Epigenetic signature of Ewing epigenomic ­characteristic profiling reveals a Fig. 26 intra-tumor). Adapted DNA methylation 2017.

Ce — M­—M­— Research Report 2017 Facts Life Science 66 67 pathways and key­pathways cellular metabolites. ­proteomes, ­ ­ interactions, designed been enable to the ofhas determination protein-protein The ­ new drugs. biology for­chemical ­ to withaccess ­(PLACEBO) inAustria provides researchers Biology for Chemical Austria The Platform in biomedicine. innext-generation sequencing specialized platform ­technology isa (BSF) Facility The Sequencing Biomedical ­partners. Medical ­ ­Medical and supporting to the at CeMM scientists dedicated are ­expertise technologies and withcutting-edge facilities research Three CeMM at Facilities University of Vienna as well as other well cooperation as as of Vienna University post-translationalcell in modifications signalling drug-protein interactions, quantitative expression quantitative interactions, drug-protein Proteomics and Metabolomics Facility (ProMet) Proteomics and Metabolomics Facility studying biologicalstudying and ­ processes

developing nently publicized (see page 19/20). nently page (see publicized both of which promi were ­PLACEBO facility, and the of Unique Drugs) Library (CeMM the saw establishment of the CLOUD 2017 therapeutic antibodies). and proteins (e.g. peptides siRNAs), nucleic test to (e.g. acids allowing application of pipeline our screening ­solutions isnow possible, inaddition DMSO to theaqueousof time, For the transfer first highly compound accelerated transfer. ­facilitates Epigenetics and Antiinfectives, Chemical for Doppler Laboratory thethrough Christian purchased system, A new acoustic transfer and developing­processes new drugs. biological for studying new targets affect that molecules small and characterize identify to high-throughput and high-contentas screening well as library a92,000-compound including biology resources chemical to access ­Austria Kubicek, PLACEBO in provides researchers Investigator Stefan ship Principal of CeMM Under theleader scientific ­collaborative basis. open the to wider community on a scientific developedand initiative has into along-term groups research and other seven CeMM Austrian between apartnership as initiated PLACEBO was Platform Austria forChemicalBiology(PLACEBO) inAustria. medicine aproof-of-conceptseek establish to for genomic projects that to contributes the BSF ­Furthermore, consulting. supportanalysis and technical ­ bioinformatic data sequencing, ­ preparation, includes robotic library 3000 and Oxford Nanopore). of services Itsrange 4000,HiSeq 6000,HiSeq NovaSeq Illumina (including instruments sequencing top-notch on several services and sequencing metagenome genome, offers The epigenome, BSF ­ and internationally. and wholeresearch genome inVienna medicine technologists, biomedical to contributes the BSF of and scientists team andBock withadedicated Investigator Christoph ship Principal of CeMM Under theleader scientific of Vienna. ­University jointly and by the CeMM Medical operated for next-generation inbiomedicine, sequencing center of expertise leading isAustria’s The BSF The BiomedicalSequencingFacility (BSF) processing, data data processing, transcriptome transcriptome single-cell single-cell - - - www.biomedical-sequencing.at/BSF or www.cemm.at/research/facilities found at: be can conditions details and contact services, its aboutMore facilities, the information CeMM systems. ­biological and lipids metabolites invarious wide-range development of workflows for the analysis of of he work metabolomics, and histeam on the head deputy As and separation techniques. etry spectrom mass profound indifferent expertise chemist with Klavins isananalytical Kristaps tools for of awide proteomics range applications. workflowsas theas well implementation of new is responsible for the of maintenance standard Currently, he settings. and­academic industrial preoteomics inboth tools, for various expert isan ­Proteomics and Metabolomics Facility, André Müller, biochemist and head of the and of speed analysis. of application,sensitivity of flexibility in terms performance provides unsurpassed (nano-LC) and nanoflow liquid(UHPLC) chromatography liquid chromatography ­ultra-high-performance with The combination spectrometers of mass instruments. MS high-end Orbitrap-based as well as systems (MS) spectrometry pole mass parkThe instrument consists of triple quadru roleactive inresearch. beyond sample on measurements andan take provides ­ withthe analysis goal extend to and Ahighly concepts. skilled motivated team and academic industrial modern incorporating laboratory, accommodated inacustom-designed technologiesProMet provides state-of-the-art (­ The ProteomicsandMetabolomicsFacility ProMet) activities activities - -

Ce — M­—M­— Research Report 2017 Facts Life Science 68 69 Investigators Principal

+ + + + + + Main Research Interests suppression and superinfections. immunopathology, hepatitis, such as ­diseases immuno ­preventive and/or therapeutic avenues for virus-induced may This pave the­computational for way novel analyses. and perturbations pathogenesisinto targeted through viral mechanistic insights gain to systems defined experimental physiological and provide human to relevance disease The employed modelspathways. ­ patho- bear experimental on and rests the interplayofmetabolic inflammatory focus ­immunology, biology. pathology and systems Aparticular ­models anintegrative approach through of virology, inmouse infections viral studies laboratory ­Bergthaler To withtheir host. of theinteractions viruses thisend, and the highly dynamic diseases ofmechanisms infectious on the molecular isfocused research Bergthaler’s Andreas for Biology inSeattle. Systems the Institute he worked of Aderem at withProf. Geneva, Alan ­University at the of Prof. Daniel Pinschewer and inthe laboratory work postdoctoral inZurich After Rolf Zinkernagel). Laureate and Nobel Hengartner Hans (Profs. university Zurich ETH Immunologyhe joined at the of Experimental the Institute studies Forhisgraduate inCopenhagen. Institute Veterinary of Tokyo,University and of the Zurich Danish the University the Edinburgh, Royal (Dick) Studies, School of Veterinary at the stays and and research spent clinical inVienna Medicine of Veterinary at the University medicine veterinary studied He joined in2011. CeMM 1977, born Bergthaler, Andreas Mechanisms of Viral Diseases Bergthaler Andreas Nat Immunol.2015;16(1):67-74. virus-induced susceptibility tobacterialsuperinfection. Schliehe C, et al. The methyltransferase Setdb2 mediates damage. Immunity. 2015;43(5):974-86. ­protects hepatocytes fromtypeIinterferon-driven oxidative Bhattacharya A*,Hegazy AN*,et al.Superoxidedismutase 1 PLoS Pathog. 2017;13(12). with thelymphocytic choriomeningitis virus L protein. Khamina K et al. Characterization of hostproteinsinteracting Relevant/Important Publications Viral evolution Transmissible cancers Metabolism and inflammation inliver and adiposetissue Immunopathologies Chronic viral infections Chromatin dynamicsin antiviral immuneresponses

­ J Clin Invest.2009;119(5):1335-49. targets of innate natural antibodies inmice and humans. Chou MY, et al. Oxidation-specific epitopes aredominant 2011;478(7367):76-81. epitopes and protectsfromoxidative stress. Nature. Weismann D, et al. Complement factor Hbindsmalondialdehyde phenotype. EMBOMolMed.2012;4(10):1072-86. and modulates plaquecompositionby skewing themacrophage Cardilo-Reis L,et al. Interleukin-13 protectsfrom atherosclerosis the ProtectiveFunctions of B-1 Cells. Cell Rep. 2016;14(10):2348-61. Promotes Atherosclerosis and Liver Inflammation by Suppressing Gruber S,et al. Sialic Acid-Binding Immunoglobulin-like Lectin G in health and disease. Nat Rev Immunol.2016;16(8):485-97. Binder CJ, et al. Innate sensingof oxidation-specific epitopes Relevant/Important Publications + + + Main Research Interests and Nature Medicine Nature including in renowned journals, fellowships authored publications and and awards has >110 won numerous has He prestigious ­Tsiantoulas 2017). et al., 2016; et al., (Gruber IgMantibodies natural well as as (­ roles IL-5 protective and of mechanisms the cytokines also­ He H(Weismann 2011). ­factor et al., 2009)and of ­ et (Chou al., antibodies natural lipid from epitopes derived peroxidation of major are targets oxidation-specific group certain that discovered research His 2003). (Binder IgMT15/E06 et al., and the natural vaccination the of ­ atheroprotective effect described first He and beexploited how these can for therapeuticinterventions. on the rolefocusing of immune inatherosclerosis functions group and aresearch leads medicine inlaboratory ­specialist Investigator. isa He 2006 he Principal joined as CeMM appointedhe in was Professor of Atherosclerosis Research, where in2009 of Vienna, University at the Medical Medicine he joined of the Laboratory In2005, Department in 2002. degree Diego, where inSan he hisPh.D. obtained ­California of at the program University hein 1997, entered aPh.D. degree where he hisM.D. obtained of Vienna, the University of Faculty at the of Medical medicine ­Following hisstudies Austria. inVienna, in1973 born Binder was Christoph Atherosclerosis andImmunity Binder Christoph et al., 2004) and IL-13 (Cardilo-Reis et al., 2012), 2012), et al., (Cardilo-Reis and IL-13 2004) Binder et al., cardiovascular diseases Discover ways tomodulate natural immunity as therapy for in atherosclerosis and thrombosis Elucidate theprotectivecapacities of natural lgM antibodies Role of innate immunity ininflammation andoxidative stress

identified the athero complement pneumo­

coccal coccal . -

Ce — M­—M­— Research Report 2017 Facts Life Science 70 71 Nat Biotech.2016;34:726-737. for large-scale validation and epigenetic biomarker ­ Bock C et al. Quantitative comparisonof DNA methylation assays esis. Science. 2016;353(6304). Specification of tissue-residentmacrophages duringorganogen- Mass E*,BallesterosI*,Farlik M*,Halbritter F*et al.(2016) CellStem Cell. 2017;19:808-822. ­dynamics of human hematopoietic stemcell differentiation. Farlik M*,Halbritter F*,Müller F*et al.DNA methylation ­disease spectruminEwingsarcoma.Nat Med. 2017;23:386-395. Sheffield NC et al.DNA methylation heterogeneity defines a ­transcriptome readout. Datlinger Pet al. Pooled CRISPR screening with single-cell Relevant/Important Publications + + + + Main Research Interests of Computational Biology (2017). Society the International of and Prize the Overton (2016-2021), Grant an ERC Starting (2015-2020), Academy of Sciences bygrant the Austrian Frontier (2009),aNew Group Medal Hahn Otto ­Society’s Planck the including Max major awards, research several and recipient of (since 2017) Academy of Sciences ­Austrian isamember He of the YoungProjects. Academy of the Genome Network inthe of International Personal partner isthe project that Austrian science acitizen Genom Austria, EpigenomeHuman and he Consortium) co-founded project (inthe International Investigator of the BLUEPRINT aPrincipal been has He for Informatics. Institute Planck Max and group adjunct at CeMM leader for at the bioinformatics Facility coordinator Sequencing ­scientific of the Biomedical of Vienna, also aguest professor University at the Medical is He genetic and diseases. rare cancer including ­medicine, inthe of context personalized CRISPR) cell sequencing, and (single- high-throughput technology ­bioinformatics, on epigenetics, focuses research His Investigator in2012. Principal joined as CeMM in1979, born Bock, Christoph Next-Generation Sequencing Medical Epigenomicsand Bock Christoph Diagnostics. Pilotprojectsingenome-based precisionmedicine Technology. Single-cellsequencingfor genomic medicine Bioinformatics. Algorithms for inferringepigenetic cell states Epigenomics. Mapping epigenetic defectsincancer cells Nat Meth.2017;14:297-301.

development. + + + Main Research Interests in2014. Academy ofmember of Sciences the Austrian corresponding ­excellent elected and scientists female was ­­2013 from of Vienna University of the theto Medical Senate appointed She was science. and basic medicine ­academic and highly committed bridging to and Disease, in Health CellCommunication of program speaker the deputy doctoral ­ She isdeanof Ph.D. the CeMM in health and disease. ­interplay of immune homeostasis tissue cellslung regulating the towards isdirected research latest Her infections. to hemolysis linking mechanisms ­molecular and susceptibility ­development group Her the recently discovered and disease. ­comprehensive inhealth, of macrophage functions repertoire on the specifically focusing ingeneral, infections ­bacterial on immune the innate to response focuses Sylvia’s research ­continued her own lab. duties while her alsorunning clinical Investigator and recently, until a Principal as CeMM she she joined In2006, of Amsterdam. at the University Ph.D. and her internist obtained isaboard-certified and Berlin, inVienna Medicine Sylvia studied of Vienna. ­University and Biology at Professor the Medical of Infection at CeMM, Affairs of Medical isDirector Ph.D., Sylvia Knapp, M.D., Innate ImmunityandBacterialInfections Knapp Sylvia and 9. JExpMed.2010;207(12):2689-2701. Baumann CL, et al. CD14 is a co-receptor of toll-like receptors7 3014-3024. by phospholipid-derived DAMPs. J Clin Invest.2013;123(7): Matt U, et al. WAVE-1 mediates suppressionof phagocytosis J Clin Invest.2013;123(8):3363-3372. and worsens pneumococcal pneumoniaoutcomes. Warszwaska JW, et al. Lipocalin-2 deactivates macrophages ­pneumococcal pneumonia. ­effector mechanisms andexertsdetrimental effectsduring Sharif O,et al. TREM-2 inhibitscomplementcomponent1q Nat Immunol.2016;17:1361-1372. to infection via disruptionof phagocyte functions. Martins R,et al. Hemedriveshemolysis-induced susceptibility the Lung ImmuneEnvironment. Saluzzo S,et al. First-Breath-Induced Type 2Pathways Shape Relevant/Important Publications Macrophage plasticity inlungdevelopment,homeostasis Impact of endogenous danger moleculesinimmunity Molecular mechanismsof host-pathogen interactions and disease – 2016, is a member of the Academia.Net circle of circle isamember of the Academia.Net 2016,

PLoS Pathog. 2014;10(6):e1004167. Cell Rep. 2017;18(8):1893-1905. program, program,

+ + + + + Main Research Interests manner. and howMPN itcould inapersonalized betreated to contributes how geneticaim is understanding variability His for MPN. new therapeuticstrategies identify MUV to continues and the at CeMM hisresearch Kralovics Robert Usinggenomic advanced approaches, in2013. gene (CALR) in2005and inthe calreticulin gene (V617F) in the kinase JAK2 causing mutations have the been identificationfar disease of major His achievementsmyeloid so ingeneral. malignancies inmyeloproliferative and in ­primarily neoplasms (MPNs) interests are research Kralovics’ Skoda inBasel. with Radek project leader he became In2001, inHouston. Medicine Professor at Baylor group Assistant College ofPrchal’s as joined In2000,Robert USA. inBirmingham, ­Alabama tive ­ on the genetics based of work myeloprolifera­doctoral was post His of Republic. the the Academy Czech of Sciences of Biophysics inGenomicsat the Institute and of his Ph.D. University at Biology andComenius Genetics Molecular degree in hismaster’s earned He (MUV)since 2017. of Vienna University since 2006and aGroup at the Medical Leader Investigator at CeMM Principal been has Kralovics Robert Genetics ofHematologicalDisorders Kralovics Robert the oncogenic functionof CALR mutants. Leukemia. Nivarthi H,et al. Thrombopoietin receptor isrequiredfor Relevant/Important Publications ­myeloproliferative disorders. NEngl J Med.2005;352(17):1779-90. Kralovics R,et al. A gain-of-function mutation of JAK2 in to myeloproliferative neoplasms. Nat 2009;41(4):450-454. Genet. Olcaydu D, et al. A common JAK2 haplotypeconferssusceptibility N Engl J Med.2011;364(5):488-90. Harutyunyan A, et al. p53 lesionsinleukemic transformation. erative neoplasms. NEngl J Med.2013;369(25):2379-90. Klampfl T, et al.Somatic mutations of calreticulin inmyeloprolif tive neoplasms. Blood.2016;127(3):325-32. novel MPL and JAK2 mutations intriple-negative myeloprolifera - Milosevic Feenstra JD, et al. Whole-exome sequencingidentifies 30:1759–1763. myelofibrosis duringMPN Identify thekey factors that initiate thrombosis and How genetic variability contributestodisease What drugscan inhibitcells with specific genetic defects respond totherapy How mutant stemcellsevolvegenetically, how they mutation-positive bloodcells How totrigger an immuneresponse against CALR disorders working with Josef Prchal at the University of working disorders at the Prchal withJosef University

2016;

- - 2015;34(29):3780-90. ­confers sensitivity toinhibitionof SUMOylation. Oncogene. Licciardello MPet al. NOTCH1 activation inbreast cancer of human pancreatic islet cell types. Li J et al. Single-cell transcriptomes revealcharacteristic features 2016;12(7):504-10. ­landscape identifiesBRD4-TAF1 cross-talk. Sdelci Set al. Mappingthechemical chromatin reactivation Impair α Cell Identity. Cell. 2017;168(1-2):86-100. Li J et al. Artemisinins Target GABAA Receptor Signaling and Biol. 2017;13(7):771-778.Nat Chem ­uncovers a synergy targeting the androgen receptor. Licciardello et al. A combinatorial screenof the CLOUD Relevant/Important Publications + + + + Main Research Interests cells. beta producing withthe­ new aimof insulin- generating tion of cell types and on incancer the transdifferentia chemical lethal targets synthetic as enzymes on chromatin-modifying focus ­Projects andcell ­chromatin inthe states. definitiontypes cellof The Kubicek­Haplogen. isworking lab on the role of ­ Boehringer CeMM, between partnership apublic-private Epigenetics and Antiinfectives, Chemical Doppler head alsobeen of ­ the Christian has Kubicek Stefan Since 2013, ­pancreatic BRD7389. alpha cells, and ­ asmall histone­selective methyl ­ in the have identification resulted ­activities of the first These Ingelheim andBoehringer at the Broad Institute. with equipped on experience for previous screening based ( and platform heads PLACEBO the screening chemical Kubicek Stefan and MIT. ofat Harvard the Broad Institute Schreiber workingresearch on biology withStuart chemical fields biology.to post molecular doctoral He thenperformed he changed inVienna, Jenuwein’sThomas at the lab IMP in For hisPh.D. Zurich. a diploma thesiswriting at ETH of Technology University the Vienna from after ­chemistry insynthetic organic anMSc obtained He 2010. in August, and joined isAustrian CeMM 1978, Kubicek, born Stefan Chemical BiologyandEpigenetics Kubicek Stefan Platform ­ ­Platform Role of chromatin inthespecification of pancreatic celltypes Chromatin incancer development and progression host factors ininfectiousdiseases Small moleculeprobesfor chromatin modifiers and Chemical epigenetics Austria for Chemical Biology), a task he iswell Biology), atask for Chemical Austria molecule inducer of insulin expression in

transferase inhibitor, BIX-01294, inhibitor, BIX-01294, transferase EMBO Rep. 2016;17(2):178-87. Nat Chem Biol. Nat Chem Ingelheim and Laboratory for Laboratory -

Ce — M­—M­— Research Report 2017 Facts Life Science 72 73 complex and Fanconi anemia. identify synthetic viable interactions betweentheBLMhelicase Moder M*, Velimezi G*,et al. Parallel genome-wide screens 2017;68(4):797-807.e7. of NucleotideExcisionRepair IsMasked by MUTYH. Mazouzi A, et al. Repair of UV-Induced DNA Damage Independent Relevant/Important Publications + + Main Research Interests diseases. hereditary rare and and other suppress tumorigenesis genomic stability ­ to cells damage respond –and to –DNA repair group the Joanna’s by which mechanisms investigates CeMM, of the immune and insuppressing system lymphoma. At (CR-UK), inthe repair development she DNA investigated UK Research Cancer (LRI), the London Institute Research of the bloodthe incancers role and at of genomic instability on she focused onpoietic thisexperience Building cells. stem hemato ­histone inmaintaining isimportant acetylation chose work to on the immune and demonstrated system that she thistime, During repair.netic DNA in modifications the investigated regulationJoanna of and epige importance where (IARC), on for Cancer WHO, France Research ­Agency workrepair. Postdoctoral followed at the International of mechanisms DNA investigating of Manchester/Sussex, Subsequently, work she commenced at the Ph.D. University moving Cyprus. there from inthe UK, studies undergraduate She completed joined her in2011. Loizou CeMM Joanna DNA Repair andGenomicStability Loizou Joanna I. 2015;11(11):e1005645. are Required toSuppress T Cell Activation. PLoS Genetics. Prochazkova J, et al. DNA Repair Cofactors ATMIN and NBS1 ATMIN. Anjos-Afonso F, et al. Perturbed hematopoiesis inmicelacking pii:S2211-1247(16)30366-7. ­Uncovers Targets for ATM and ATMIN. Response to Aphidicolin-Mediated Replication Stress Mazouzi A, et al. A Comprehensive Analysis of theDynamic during somatic recombination Repair of physiological DNA breaksinimmune T and B cells pathways inhumandisease Genome integrity and cooperation betweenDNA repair Blood. 2016;128(16):2017-2021. Nat Comm. Cell Rep. 2016; 2017;8(1):1238. maintain maintain Mol Cell.

­

- + + + Main Research Interests by the ­ Groups for Young integration grant career Investigators group Research issupported research by aVienna His interactions. of principles the drug-drug basic ­understanding group and network-based are approaches diseases rare to Two screening. chemical of major interest of his areas high-throughput to proteomics andand transcriptomes, next-generation offrom genomes, sequencing epigenomes post-genomic employ, technologies researchers CeMM that of the powerful broad from range derived datasets the large computational approaches help to and interpret understand applies He Investigator in2015. diverse Principal as CeMM joined Jörg of the (patho-)physiological basis tutes states. constithe that molecules complex of interacting machinery applied tools and elucidate to concepts network theory from he Institute, Cancer Farber Dana from School Vidal and Marc Medical Harvard from ­collaboration withJoseph Loscalzo Inclose Institute. Cancer Farber Biology at Dana ­Systems and at the for Center Cancer University at Northeastern fellow workto apostdoctoral withAlbert-László Barabási as innetwork theory. then He moved Boston to he specialized of Colloids inPotsdam Institute Planck ­Max and Interfaces at the Lipowsky withReinhard hisPh.D. During ­Berlin. and Recife physics inLeipzig, MencheJörg studied Network Medicine Menche Jörg Human Zhou XZ*, Menche J *,Barabási AL, Sharma A. 2015;347(6224):1257601. through theincompleteinteractome. Science. Menche J, et al. Uncoveringdisease-disease relationships Nat Comm. Guney E,et al. Network-based insilicodrugefficacy screening. NPJ Syst Biol Appl. 2017;3:10. ­expression profilesintopredictivedisease-associated gene pools. Menche J*, Guney E*et al. Integrating personalizedgene to humandisease. Curr OpinSyst Biol.2017;3:88. Caldera M*,BuphamalaiP*et al. Interactome-based approaches Relevant/Important Publications exploring large datasets Virtual reality approaches for visualizing and Basic principlesof drug-drug interactions Network-based approaches torare diseases Science and Technology Science Vienna (WWTF). Fund ­symptoms disease network.Nat Comm. 2014;5:4212. 2016;7:10331. - + + + + Main Research Interests microscopy.automated confocal using patientfor material the of screening liquid primary lipids and the development of “­ of the higher-level cells, machinery of organization akey are componentdiscoveries of the nutrients-sensing Recent action at level. the molecular the of mechanism drug and the development approaches of integrated understand to of principles the proteomeorganization of higher organisms of fundamental the discovery inhuman cancers, ­kinases of mechanisms tyrosine elucidation of regulatory basic major achievements His scientific includedate to the ERC. appointedof the Council he was of Member the Scientific Investigator 2017, and 2Proof-of-Concept InJanuary Grants. 2ERC obtained Advanced the Year”. Giulio Superti-Furga ­ Natural for of Vienna of the City the received Prize Republic, Italian awarded the title of Commander of of the the of Order Merit was He of Vienna. University at the Medical ­Pharmacology Europaea and and isProfessor Academia for Systems ­Sciences, ­ ­Sciences ­ the Austrian isamember He of EMBO, of CeMM. Director been he has Since 2005, ­companies Cellzome, Haplogen and Allcyte. the co-founded He biotech leaderand at EMBL. team fellow apostdoctoral was He and IMP/Vienna. Genentech Zurich, ­biologist. completed He at the University hisstudies and systems molecular isanItalian Giulio Superti-Furga The ActionMechanismofDrugs Superti-Furga Giulio Nature. 2012;487(7408):486-490. molecular network by common and uniquestrategies. Pichlmair A, et al. Viral immunemodulators perturbthehuman Nature. 2015;519(7544):477-81. amino-acid-sensing machinery that controlsmTORC1. Rebsamen M,et al. SLC38A9 is a componentof thelysosomal 2015;162(1):170-83. lipids modulates innate immuneresponses. Cell. Köberlin MS,et al. A conservedcircular network of coregulated 2017;13(6):681-690. ­immunomodulatory potentialof commondrugs.Biol. Nat Chem Vladimer GI,Snijder B, et al. Globalsurvey of the Relevant/Important Publications Cell gates and cellmetabolism Molecular basisof innate immunity Molecular networks affecting leukemia Mechanism of action of drugs Sciences and in 2011 became “Austria’s of became Scientist and in2011 Sciences Leopoldina, the Academy of European Cancer Leopoldina, Academy of Sciences, the German Academy of the German Academy of Sciences,

pharmacoscopy”, a technology technology a pharmacoscopy”,

­membrane 2012;8(11):905-912. drug ­ Winter GE,et al. Systems-pharmacology dissectionof a mediated DNA damage toxicity. Winter GE,et al. The solutecarrier SLC35F2 enables YM155-­ Target ProteinDegradation. Science. 2015;348(6241):1376-81. Winter GE,et al. Phthalimide Conjugation as a Strategy for in vivo in acute leukemia. Erb MA,et al. Transcriptional controlby theENL YEATS domain ­recruitment. ­master transcription elongation factors independentof CDK9 Winter GE,et al. BET bromodomainproteinsfunction as Relevant/Important Publications + + + Main Research Interests therapeutic strategies. personalized ultimately to regulation contribute novel, to withmedicine Ultimately,level. ingene research basic hisgoal connect isto regulation at kinetic ahigh resolution and on asystems-wide of and principles transcription gene fundamental ­disrupts and studies lab His anoncogenicorder state. sustain to in how networks rewired are understand to transcriptional develops lab His and applies probes chemical in June 2016. Investigator Principal aCeMM as recruited was Winter Georg of the to leukemic study gene regulation. this strategy solution protein and degradation invivo applied to target pharmacological he innovatedageneralizable There, School. Medical Institute/Harvard Cancer Farber at the Dana Bradner biology, fellow working apostdoctoral withDr. James as combinations. continued He inchemical drug histraining synergistic and elucidating mechanisms on mechanistically resistance genetic chemical approachesas drug identifying to inproteomics well as specialized He at CeMM. Superti-Furga under the of supervision anti-neoplastic Prof. Giulio drugs working the of onof mechanism elucidating action Vienna, of ­ the Medical from hisPh.D. obtained Winter Georg Chemical BiologyofOncogenicGeneRegulation Winter Georg Pharmacologic disruptionof transcription Oncogenic gene regulation and genome organization Chemical biology and chemical genetics synergy inimatinib-resistant Biol. CML. Nat Chem Mol Cell. 2017;67(1):5-18.e19.

Nature. 2017;543(7644):270-274. Nat Chem Biol. 2014;10(9):768-73.Nat Chem University University

Ce — M­—M­— Research Report 2017 Facts Life Science 74 75 2015;407(1):40-56. ­Diaphragm Developmentinthe Mouse. Developmental Biology. Paris ND, et al. Wt1 and B-Catenin Cooperatively Regulate PloS Genetics. 2015;11(10):e1005525. by Regulating MicrotubuleDynamics and Cellular Proliferation. Coles GL,et al. Kif7Maintains Respiratory Airway Architecture 2017;10(8):955-970. ­hernias: fromgenes tomechanismstherapies. DisModelMech. Bogenschutz E,Sun X, Chung WK. Congenital diaphragmatic Kardon G, Ackerman KG, McMulley DJ, Shen Y, Wynn J, ShangL, Relevant/Important Publications + + + Main Research Interests School. and Medical Women’s Hospital/Harvard fellowships and research at Brigham Hospital, Children’s at Boston Denver, Care) Colorado, fellowship clinical (Critical in residency pediatrics at Buffalo, degree at the University degree University, at Cornell her medical her undergraduate She completed inchildren. illness critical cause that defects on genetic and developmentalfocused of mechanisms birth previously has research Kate’s (FOPO). ­Organizations and the Board of the of Federation (SPR) Pediatric Research Officer/Sec-Treasurer forPediatric for the Society and Operations the Strategic at The Jackson Laboratories, (MGD) board forthe advisory the Genome Mouse Database and Development, Human Health ofNational Child Institute Counselors Board offor Scientific theEunice Kennedy Shriver holds many other and leadership roles advisory the including Inaddition Kate the to Societies). meeting, PAS ­Academic meeting Pediatric (PAS, Research Pediatric international leadership roles of the includes largest organization Kate’s one of Inthe USA, of life. period the perinatal events during critical from resulting disease ofmechanisms long-term Knapp potential on epigenetic projects aimed at identifying worked and Bock Sylvia of Christoph withthe laboratories she at CeMM, and While innovation. strategy in research, withleadership and roles Genetics Biomedical Care) (Critical Professor of Pediatrics anAssociate She iscurrently CeMM. Investigator at Guest isarecent Principal Ackerman Kate Adjunct PrincipalInvestigator Ackerman Kate in children and adults with isolated birthdefects Genetic and epigenetic mechanismsof co-morbidities the pulmonary system Developmental originsof health and diseasein of thelung, heart and diaphragm Gene identification anddiseasemechanismsfor diseases

immunity. Recently, inmultiple ­ international ofpathomechanisms disorders hematopoiesis of rare and biology approaches the genetics and understand to molecular biological and molecular sequencing withsystem techniques combines next-generation laboratory His DE. School, ­Medical and ­ ­ Research Campbell at the Scripps L. withIain training his graduate of at the Universities Medicine studied He in 2011. ­Investigator Principal joined as CeMM 1977, born Boztug, Kaan Adjunct PrincipalInvestigator Boztug Kaan homeostasis and congenital neutropenia. Boztug K,et al. JAGN1 deficiency causes aberrant myeloidcell Infections. NEngl J Med.2015;372(25):2409-2422. Inherited DOCK2Deficiency in Patients with Early-Onset Invasive Dobbs K*,Dominguez Conde C*, ZhanS-Y*, Parolini S*,et al. 2016;17(12):1352-1360. with impaired cytoskeletal dynamics. Nat Immunol. Salzer E,et al. RASGRP1 deficiency causes immunodeficiency N Engl J Med.2017;377(1):52-61. ­early-onset protein-losing enteropathy, and thrombosis. Ozen A*, Comrie WA*, Ardy RC*,et al. CD55 deficiency, Relevant/Important Publications + + + Main Research Interests (ERC). Council of Grant the Research European and aStarting (FWF) Fund Science of the Austrian he the received START Prize In 2012, Hospital. Children’s Anna ofand isHead Immunology at St. and Oncology Hematology inPediatric aconsultant and as and Adolescent at MedUni Vienna Medicine of Pediatrics Professor holds appointment adual Boztug Associate as Kaan director. for (LBI-RUD) which as he acts Diseases ­Undiagnosed for Ludwig Rare Boltzmann Institute ­dedicated led aproposal for of and successfully a erection ­Diseases and Undiagnosed forof Center Rare the CeRUD Vienna He isdirector and others. deficiency NIK JAGN1 deficiency, PRKCD deficiency, DOCK2 deficiency, deficiency, ­RASGRP1 immunodeficiencies including CD55­ human ­ several his group and characterized discovered 2014;46(9):1021-7. targeted treatment of rare and undiagnoseddiseases Systems biology and network medicinediagnostics and autoinflammation Molecular mechanismsunderlying autoimmunity and disorders of hematopoiesis and immunity Genetics and molecular pathophysiology of rare inherited Dusseldorf, Freiburg (DE) and (DE) London (UK),followed Freiburg ­Dusseldorf, by clinical training with Christoph Klein at Hannover withChristoph training clinical Institute, La Jolla, USA and postgraduate research research and postgraduate USA Jolla, La Institute,

Nat Genet. deficiency, collaborations, collaborations, primary novel primary

and

+ + + Main Research Interests and EMBO’s gold received in2013. medal (2005) Technology magazine Review byInnovators MIT’s one chosen as of theBiology), heworld’s was top 35Young and for Molecular Biochemistry Association Dutch (2004, ­ van he the received Antoni Forhisstudies, ­Investigator at CeMM. Principal anAdjunct and he became Institute Cancer moved the to Netherlands hislaboratory and in2011, USA, hisindependent initiate to inCambridge, program research appointed aWhitehead Fellow he was as In2004, Bernards. of Prof. Rene inthe laboratory ­Netherlands Institute Cancer at the research hisgraduate and did in1998 Amsterdam University, the inbiology Free from hisM.S. received He the receptor long-sought for intracellular as virus. Ebola NPC1 the ­ host ­ tify thisapproach used iden to has He mutagenesis. insertional approach for haploid genetic inhuman screens cells using developed More recently he has an interference”. RNA enabling gene inhibition molecules, shRNA “stable through he developed for the studies asystem expression of his Ph.D. During action. and drug disease infectious research, ­cancer interests are His playgenes that arole inhuman disease. genetics inhuman cells pinpoint to uses Brummelkamp Thijn Adjunct PrincipalInvestigator Brummelkamp Thijn ­transporter Niemann-Pick C1. Carette JE,et al.Ebola virusentry requires thecholesterol ­haploid humancells. Science. 2015;350(6264):1092-1096. Blomen V, et al. Geneessentiality and synthetic lethality in of Picornaviridae. Nature. 2017;541:412-416. Staring J, et al. PLA2G16, a Switch betweenEntry and Clearance 2017;546:307-311. states reveal an off-switchfor GPCRsignalling. Nature. Brockmann M,et al. Genetic wiring mapsof single-cellprotein activity. Science. 2017;pii:eaao5676. Nieuwenhuis J, et al. Vasohibins encodetubulindetyrosinating Relevant/Important Publications Drug action Infectious diseases Cancer research identification of thecholesterol lysosomal transporter Leeuwenhoek Award (2003), the Award NVBMB Annual factors used by a variety of which pathogens, led to by avariety used factors

Nature. 2011;477(7364):340-343. - Neurology. 2000;54(12):2212-2217. the levelsof Alzheimer’s amyloid beta peptides inbrain. Petanceska SS, et al. Ovariectomy and 17beta-estradiol modulate J Neurosci. 2006;26(7):1923-1934. ­Hippocampal Late-Phase Long-Term Potentiation and Memory. Nagy V, et al. Matrix Metalloproteinase-9 IsRequired for for long-term memory. Learn ase- 9is activated by inhibitory avoidance learning and required Nagy V, et al. The extracellular proteasematrix metalloprotein 2011;471(7340):637-641. ­complex regulating NF-κB activity and apoptosis. Nature. Ikeda F, et al. SHARPINforms a linear ubiquitinligase ­perception. Cell Cycle. 2015;14(12):1799-1808. ­factor PRDM12 controlssensory neurondevelopment and pain Nagy V, et al. The evolutionarily conservedtranscription Relevant/Important Publications + diseases + + Main Research Interests screens. neuropathologies drug rare for well targeted as as identified in variants of genetic causative analyses ­perform inorder platform screening to culture-based ­neuronal, herIn addition, group up issetting primary, anautomated, andmodels cellular molecular characterization. detailed to behavioralapproach, of genetic phenotyping from mouse pathophysiology,­disease her group applies amultidisciplinary underliethat neuropathologies. rare To into insight gain genes causative of her and group characterize identify isto the aim LBI-RUD, At system. of the nervous functions basic of mousephenotyping models of genetic affecting disorders on preclinical she focused and memory.learning InAustria, synaptic remodeling and functional underlining structural anoveldescribed roleproteolysis for supporting extracellular and neuroscience molecular basic Vanja studied USA, Nagy Inthe in2016. Researcher Key as Diseases and Undiagnosed She joined for the Ludwig Rare Boltzmann Institute ­Austria. Biotechnology, for at Molecular the Institute Penninger and Josef Croatia, Sciences, for Life Institute ­Mediterranean she worked at the Dikic training, withIvan her postdoctoral For USA. at Mount Schoolat of the Sinai, Icahn Medicine Sciences Biomedical inBasic Vanja her Ph.D. obtained Nagy Adjunct PrincipalInvestigator Nagy Vanja Basic molecular mechanismsunderliningsynaptic plasticity Cellular and molecular basisof rare neurodevelopmental Preclinical phenotypingof rare neuropathologies

Mem. 2007;14(10):655-664.

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Ce — M­—M­— Research Report 2017 Facts Life Science 76 77 Joanna I.Loizou, Vanja Nagy. Robert Kralovics, Jörg Menche, Kaan Boztug, Thijn Brummelkamp, Giulio Superti-Furga, Stefan Kubicek, Sylvia Knapp, Christoph Binder, Kate Ackerman, Christoph Bock, Andreas Bergthaler, Georg Winter, from toplefttobottomright

Ce — M­—M­— Research Report 2017 Facts Life Science 78 79 opportunities. opportunities. and commercialization transfer on technology provide recommendations management CeMM and students to fellows and­postdoctoral Ph.D. faculty, plans withCeMM research future provide feedback on ongoing discuss to projects, to visitthe Board members institute ­Advisory ­bio immunology, and biochemistry medicine, biology genetics, to molecular from expertise of abroadnational range top covering scientists its stakeholders advised are by a board of inter CeMM and andquestions, In scientific strategic Scientific Advisory Board informatics. Every 18 months, 18 the Scientific Every ­informatics. ­ Director Giulio Superti-Furga. Director itsScientific by would face intheupcoming period, CeMM that opportunities and the challenges of acompendium wellas preceding months 18 as covered the that report provided withawritten of publications.including We alist also been had groups, of theten reports with theindividual mail thedocumentation obtained by ­previously 2017. We had 12, 9to April April from CeMM Board visited Advisory Scientific CeMM The Board: Advisory of the Scientific report of the 2017 part) (general Excerpts ­inspiration and motivation. and ­ the lively withour researchers interactions feedback member of SAB and each for critical for We the CeMM. to grateful are importance Board visitsare of great Advisory The Scientific students whichstudents source aninvaluable of are fulfill itsmission. ­fulfill to allow to grow CeMM thereby and capacity their resources. We other and reviewed facilities of the appreciation adetailed and mentoring, of thetraining and quality the plans, ­scientific of theambitiona good scope and sense of future of We research projects. also developed majority into insight the detailed developed we All inall, institution). mother (CeMM’s Infrastructure and of Institutes director of Sciences, Academy theAustrian from ­Echinger We aclosed also had session withDr. Stefan individually. members faculty all10 interviewed we Finally, of faculty. in theabsence postdocs and withthestudents to meet theopportunity us gave schedule The laboratories. different theten from fellows postdoctoral and Ph.D. by students talks short were of thepresentations remainder The Collaborative Programs”.for thethree “Strategic We of progressnities. also heard summaries made opportu development translational business and Investigator, Winter, Georg asession and on the hired themostrecently by Principal ­presentation alonger review, under of theperiod Director theScientific by including anoverview entations, to atotal of 39pres listened we inVienna, While - - f. e. d. c. b. a. 1. opinion all. of aconsensus us represents and of theconclusionsessence of members theSAB the fashion, inconcise summarizes, report This when it was created. itwas when one ambition ago years itsnumber ~10 was which research, indisease-focused excellence of center which allows atrue out as itto stand science, mostprominently, itsoutstanding And, inEurope. known research Institutions better witholder, comparison by and larger ­especially the impressive of itspublications standard levels reached enviable has that Its success grant incompetitive funding Asia. and inEurope, America, universities and Institutes those of larger,rival endowed older, better and whose published discoveries the CEMMfaculty, of success intheresearch level of A rapidly rising PD and Fellows. of body graduate students bright extraordinarily and interactive sophisticated, enthusiastic, home to anenviably It being itsscience. ­characterizes of success and theongoing that excellence high level a remarkably reflecting meeting SAB itsrecent at All of itsresearch presentations Science atCEMMisexemplifiedby: Nadia Rosenthal. Carl-Henrik Heldin, Hidde Ploegh, David Livingston, Janet Kelso, f.l.t.r: RichardFlavell, Board ­Advisory The CeMMScientific

Ce — M­—M­— Research Report 2017 Facts Life Science 80 81 e. d. c. b. a. 3. d. c. b. a. 2. these aims. these begunto already fulfill has young institution, avery being despite CeMM, that believe we said, That them. achieve actually few very while goals, these to compete realize institutions Many such academy. or learned ­establishment top goal of any national research support outcomes improvesand should patient bea ­ new application and of discovery that ­believing Weexpectations, are confident inthese impact. which should translate into major international inAustria and research inVienna centered ­ of translational and success to disease- basic levels greater whoAnd ever promise to bring to and CeMM ­interactivity commitment to intheir and ­collegiality intheir unselfish while being own right, each inhis/her areWho both hugely successful, its cadre of group leaders of and retention recruitment identification, inthe taste shown extraordinary ithas That leadership scientific remarkable It’s We attributethesuccessofCEMMto: grants, and other metrics of scientific of scientific metrics grants, other and of publications, intheform evidence objective indisputable and review theSAB at of CeMM scientists withthetalented encounters our direct on isbased our that judgement We emphasize science apivotaland component of Austrian CEMMisof value to high that reports Academy future recognition justifies in success richly of scientific level itsremarkable We that believe years. recent in of which witnessedemerging have we thedevelopment itisanachievement, Indeed, lightly not use do we that isamoniker treasure’ A ‘national immense complexity. Andwewishtoaddthat: care ofbothcommonandrare diseasesof are likely, intime, tosignificantly improvethe time. We anticipatethatsomeofitsdiscoveries ­biomedical researchandhasdonesoinrecord has becomeanationalscientifictreasurein We areunanimousinouropinionthatCEMM information that advances medical science medical science advances that information ­achievement. h. g. f. e. d. c. b. a. 5. d. c. b. a. 4. this kind. of developments We strongly encourage further economic and benefits. societal attendant withremarkable, science, inbasic and medicine promises to yield breakthroughs intranslational thecollaborationWe that believe envision we institutions. the work theresearch and ambitions of both will significantly compromise research enterprise MUV-CEMM collaborative ­ effective and less anything afull than that We worry research ­success indisease-based itsnational ambitions of to realize for Austria inorder essential as view we development of avibrant collaboration.ment bilateral This develop transparent and efficient, of thefull, CEMMwill theMUVand reap thebenefits Both research. medical care throughin advancing incisive successful to befully industry and institutions collaborating withother also interact must partners, core, working CEMM, theMUVand as its At collaborative­MUV-CeMM enterprise. We anecessarily such research view as CEMMtranslationalMUV and research. a physical to accommodate expansion future theMUVisplanning when atime at ­institutions theresearch of both energize can further MUVfaculty, and CeMM of several on thepart of effort and time investment involve substantial collaborations,These which will continue to of Austria. to the citizens of medical benefits ­accelerate thedevelopment will This ­application both at institutions. research itsclinical and disease-based edge, cutting to enrich opportunities new Offers intheforeseeable future, developed ­collaborations if successfully withtheMUVthat, vital to establish efforts itsbest It isusing this key challenge. But therearesignsthatCEMMisrisingto years. few thepast during theAcademy by provided of funding level thestatic by ­hampered been have potential ­mission scientific and its to fulfill itsability thereby, and, CeMM at research scientific future that We also worry hard to come by. into human clinical applicationdiscoveries are intranslating itslaboratory-based successful theresources to needed when atime be at And itsyoung away vibrant and faculty recruit to competing are actively Europe America and in institutions larger other when atime At discovery research-driven of medical level itsremarkable In sustaining CEMM stillfaces dauntingchallenges: translational - Australian Regenerative Medicine Institute, Institute, Medicine Regenerative Australian Professor, Adjunct Harbor, Bar USA, Genetics, for Mammalian The JacksonDirector, Laboratory Nadia Rosenthal, Ph.D. USA Cambridge, Research, ­Biomedical for Member, Whitehead Institute ­Hospital, Boston Children’s of Medicine, Department Investigator, Division Biology, of Molecular Hidde Ploegh,Ph.D. USA Boston, Institute, Cancer Dana-Farber Director, Deputy School, Medical Harvard Professor, Genetics, David Livingston,M.D. chair DE Leipzig, for Evolutionary­Institute Anthropology, Planck Max Group Bioinformatics, Leader Janet Kelso, Ph.D. Board of the Nobel Foundation Member, SE Chairman, University,Uppsala SE, Research, for Cancer LudwigDirector, Institute Carl-Henrik Heldin,Ph.D. USA Haven, New Yale ­ of Immunobiology, Section Chair, Institute, Investigator, Medical Hughes Howard Richard Flavell,Ph.D. Submitted, Respectfully www.cemm.oeaw.ac.at/about/advisory-board website: visittheBoard please of CeMM CeMM For moreAdvisory on the information Scientific College London, UK Imperial Institute, &Lung National Heart Science, AU, Cardiovascular ­Melbourne, Chair, University School of Medicine, School of Medicine, University

Ce — M­—M­— Research Report 2017 Facts Life Science 82 83 Obituary Imperial ­Imperial at the Hogan withBrigid studies ­doctoral post at Warwick University. She performed in thenurse UKbefore completing her Ph.D. Barlow Denise registered worked astate as Denise P. Barlow We have lost mentor, agreat role a female model and abeloved friend. researcher, awoman pioneer leadership. inscientific extraordinary The ­ of Vienna. the University Professor heruntil ofat retirement and Genetics Honorary in2015 ­Denise P.ofDenise Barlow, Wedecease the in2017. who us mourn left of the ­ one made Denise of persistence unique type and her spirit personal Her Biol,(RNA 2015). a biological problem withher own eyes” by her see “to passion driven and was instead follow to trends or“fashion” refused scientific clearly one She of always was akind. Denise achievements. ­Achievement Award for Medal her lifetime Chapter and the EMBO/EMBL Austrian Academy of of Sciences the Austrian Prize Schrödinger Barlow theDenise received Erwin In2014, of Vienna. at theGenetics University Professor anhonorary of and was since 1995 ­retirement She EMBO been member had in2015. Investigator her until aPrincipal as CeMM joined Denise In2003, inSalzburg. Sciences Academy of Biology of theMolecular Austrian of­Developmental at the Genetics Institute appointedwas head of of the Department and inAmsterdam and the NKI in Vienna heldDenise group leader positions at the IMP ­ and with Hans leading geneticists of geneticists our time. leading Cancer Research Fund inLondon, Fund Research ­Cancer

was Principal ­ was Lehrach at the EMBL, Heidelberg. Heidelberg. at the EMBL, Lehrach CeMM from the very beginning beginning the very from Investigator at CeMM scientific community has lost an has community scientific passion andpassion love. intellect, Denise’s remember andalways cherish We all. us shaped and comfort will zones, mental common timesame dogmas, belief challenging on supporting people, her while at the focus rity, integ and herpersonal scientific spirit, Denise’s and success. culture significantly CeMM’s defined forexcellence scientific work and exacting ethics not itwere does if Barlow. for Denise passion Her To thisday, would CeMM not the it way operate cancer. such as a role inhuman diseases the goal of under intoresults the mouse and human genome with ­epigenetically these genes and silence extended how continuedher lncRNAs lab dissect to on the model­Capitalizing of genomic imprinting, gene expression indevelopment and disease. mouse and human of genome regulators as ­investigate throughout act how the lncRNAs led to the team (lnc) has ­non-coding RNA is induced by expression of long anunusually ­ that group’s Her subsequent finding ­mechanism. of the imprinting details many fundamental continued work to relentlessly uncover to Denise 1991). gene expression (Nature, specific imprinted show to gene inmammals parental- the first by identifying discovery breakthrough Barlowmajor Denise made her first In 1991, epigenetic silencing ofepigenetic thisimprinted gene silencing standing how lncRNAs play how lncRNAs ­standing October 21st,2017 January 31st, 1950 – Denise P. Barlow -

Ce — M­—M­— Research Report 2017 Facts Life Science 84 85 Life at CeMM Life Facts “The Medical University of Vienna can look can of Vienna University Medical “The way forway the development of new diagnostic pooling of resources, andpooling patients –and of resources, will from theprofitclose collaboration and the and Undiagnosed Diseases pave the Diseases and Undiagnosed Rare methods and personalized treatments. We treatments. methods and personalized the like Biomedical ment of facilities shared the establish­ withboth institutes, leaders The double affiliation research. of group increasingly strategic level!” strategic increasingly more alsoon an collaborative projects, Vice Rector of theMedical University of Vienna Dr. MichaelaFritz Sequencing Facility, and joint such Facility, efforts Sequencing this highly successful relationshipthis highly successful on many back on a fruitful relationship withCeMM back on afruitful over the last decade. Science and scientists Science decade. over the last the Ludwig Boltzmann Institute for the Ludwig as Boltzmann Institute are very much continuing to looking very are forward from doalready the –profit translational

Ce — M­—M­— Research Report 2017 Facts Life 88 89 “CeMM plays a distinct, special role among special plays adistinct, “CeMM Austria. Itsroots both are inthe Viennese Austria. team inthe and eighties team many CeMM IMP district, as a result of aresult itsoverly as important 9th district, major contributions revivethe to synergy human pathophysiology. Additionally, members ofmembers community, the scientific CeMM and GiulioCeMM Superti CeMM scientists act as personal bridges bridges personal as act scientists CeMM Group Leader, Max F. Perutz Laboratories, Business Angel, Vienna Professor GustavAmmerer, Ph.D. Superti and inVienna institutes science the life been an effective ingredient of Austria’s of ingredient Austria’s aneffective been between hard between music, art and science, which has always always which has and science, art of music, strategic locationand strategic withinthe hospital University withthe Medical association everyone benefits from.” benefitseveryone culture. It is a recipe for that success Itisarecipe culture. campus, and the 3rd district, as Giulio as and the 3rd district, campus, scientists were trained there. As lively As there. trained were scientists Furga was among the founding was -Furga core molecular sciences and sciences -core molecular Furga have made -Furga

Ce — M­—M­— Research Report 2017 Facts Life 90 91 “Although already has CeMM young, still European life science community community science life The European producing landmark contributionsproducing in papers, explaining new molecular explaining new molecular papers, is making the difference. Unprecedented, theis making difference. by Motivated the creativity science. life mechanisms of disease, providing asolid ofmechanisms disease, findings into tangible into developments findings CeMM scientists are committed are go to scientists the CeMM Chairman Boardof Directors, eu-life Managing Director, VIB Belgium Jo Bury, Ph.D. lead to patient diagnosis and treatment. and patient to lead treatment. that diagnosis basis for thebasis development of new therapeutic avenues. And this is precisely where Andavenues. thisisprecisely CeMM and CeMM inspiration of itsleaders, applauds such abold endeavor.” developed into atop extra mile to translate their basic research research their basic translate to mile extra with a series of breakthrough out with aseries stands notch institution, -notch institution,

Ce — M­—M­— Research Report 2017 Facts Life 92 93 “In the field of basic medical research, theresearch, field “In medical of basic period of time. However, what CeMM has of However, time. has period what CeMM years are usually not regarded as along not as regarded usually are years 10 is nothing less than outstanding. Our motive Our is nothing outstanding. than less research landscape but alsothe landscape wholeresearch of for and on everyone CeMM wishing Giulio Managing director of the Austrian Research Promotion Agency (FFG) Dr. HenriettaEgerth the future, and not only the Austrian the future, Superti achieved in the short period ofachieved itsexistence inthe short period driving force of fordriving the medicine precision society will benefit fromresearch.” its benefit will society workCeMM isa ispurelysuccessful selfish. Furga’s team many more team of years -Furga’s

Ce — M­—M­— Research Report 2017 Facts Life 94 95 “The European Research Council has been been has Council Research European “The participation of faculty as panel as members.” ofparticipation faculty bethe to problem seems eyes’ withdifferent at the same ‘Looking fellows. postdoctoral practice to support frontier research from from support to frontier research practice I am looking forward to active future future active to I amlooking forward interactions with the CeMM community, withtheinteractions CeMM at CeMM. team national and interdisciplinary faculty, among which manyfaculty, ERC grantees, May, impressed last me visitCeMM to Iwas of the scientific relying on the vitality President of theEuropeanResearch Council Professor Jean-PierreBourguignon ERC since January 2017. When he invited 2017. the ERC since January Giuliothe Superti beginning. by a continuous flow of ERC applications, by the collaborative spirit within CeMM’s by withinCeMM’s the collaborative spirit of Council amemberbeen of the Scientific well as among the Ph.D. students and students among well as as the Ph.D. great ERCgreat driving force fordriving the of success the inter­ community to establish principles and principles best establish to community supported research and -supported research Furga has has -Furga

Ce — M­—M­— Research Report 2017 Facts Life 96 97 “As a partner institute withinthe“As EU institute apartner with specialized training and aguideline training on with specialized provide the other LIBRA partner institutes provide institutes partner the other LIBRA Europe, CeMM has made impressive steps has CeMM Europe, LIBRA project, CeMM has committed a to has CeMM project, LIBRA unbiased, objective and transparent objective and transparent unbiased, is amongst the initsfield.” top centers that institute andmodern inclusive research most by step committing important bea to and made the first has but CeMM research, We reaching from far are recruitment. recruitment strategy, supporting its strategy, recruitment major improve to change institutional and LIBRA Project Coordinator chair of theERC Working GrouponGender Balance, member of theERC Scientific Council, the Centre deRegulació Genòmica (CRG)Barcelona, ICREA Research Professor and GroupLeader at Prof. Isabelle Vernos, Ph.D. their individual worktheir individual towards amore andtowards objective unbiased the EU other 13leading of the project and I am especially happyof the projectand Iamespecially about the efforts that CeMM has made to has about CeMM the that efforts gender equality on in including alllevels, gender equality gender equality and diversity. Together and diversity. gender equality with experimental design. I am very pleased to to pleased Iamvery design. experimental employees in various matters to improve to employees matters invarious considering theconsidering and sex gender dimension in see how CeMM has developed howsee has since CeMM the start life balance, and balance, -life LIFE institutes in institutes -LIFE

funded -funded

Ce — M­—M­— Research Report 2017 Facts Life 98 99 and Workshops Viennese ­ ­Viennese Academy of Sciences. Named inhonorAcademy the of Landsteiner, of Sciences. Karl A fine blend topof This includes, first and foremost, the Landsteiner Lecture, our Lecture, Landsteiner and the first foremost, includes, This Technology) lecture series addresses contemporary challenges of challenges contemporary addresses Technology) series lecture and Research Twice Art, Medicine, ayear, the S.M.A.R.T. (Science, year, providing a broad range of opportunities foryear, keep to of scientists providing opportunities abroad range ­workshops, symposiums throughout andmeetings scientific the well as to establish a dialogue withthe adialogue broader public. establish to well as Reaching outReaching the to public and abroader to communicating science up to date onup developments the date to latest intheir fields expertise, of in 2017 bear witness to our to witness dedication these to goals. bear in 2017 front ofin front amixed audience of and scientists laymen. Symposiums Lectures, thoughts and ideas. audience, fostering scientific education and connecting scientists educationscientists and scientific of connecting fostering audience, highlight held highlight ­annual at the baroque of festive hall the Austrian different disciplines are stated goals of CeMM. The 32 lectures, The 32lectures, goals of CeMM. stated are disciplines different encouraging us in our efforts to make CeMM ahub of make to inour CeMM efforts for us the sharing encouraging and well allover Vienna audiencesbeyond, from events attract expand scientific These their collaboration. networks and strengthen symposiums, seminars and scientific meetings andheld meetings scientific seminars at our institute ­symposiums, significant impact on medicine are invited to hold this lecture invited are impactto ­significant on holdmedicine this lecture isdeemed a whose have to ­scientists had research molecular science & society, it seeks to encourage out itseeks encourage &society, to science of approach. Poised at the interface aninterdisciplinary using ­science physician who discovered blood types, prominent physician who blood discovered types, class speakers hold speakers numerous-class seminars, -of

-the -box thinking as as -thinking Academy of Sciences was filled to the last seat seat filledto the last was Academy of Sciences On May 15, 2017, James “Jay” Bradner, President James “Jay” 2017, May 15, On with Chemical Degraderswith Chemical Taking outthe Cell Garbage 11th CeMM Landsteiner Lecture – whose shoulders every new modern medical medical whose new modern shoulders every witha when opened Dr. the Bradner lecture of the Novartis Institutes for BioMedical for BioMedical Institutes of the Novartis Lecture. Using an approach called “targeted Using anapproach “targeted called Lecture. decades, particularly in targeted therapy, intargeted Bradner particularly decades, execution. This alsoholds This for one­execution. true of the cant progress made in cancer therapy over made the progress incancer cant last of the­ signifi Followingcancer. summary abrief always has progress medical insulin –real like historical overview and recalled the giants on and recalled overview ­historical From vaccines to antibiotics to biomolecules to vaccines From held Landsteiner CeMM the 11th (NIBR), Research approach: targeted protein degradation. approach: targeted isbuilt. discovery achievement indrug presented an altogether different, unprecedented presented analtogether different, of our time: most diseases researched extensively innovation of principles medical and illustrated anexample,­protein Jay degradation” as Bradner their impact on allof The stunningly humankind. been achieved by radically new ideas and new incisive ideas achievedbeen by radically beautiful baroque festive hall of the Austrian baroque of festive hall the Austrian beautiful 2017, hismusic an delighting2017, and mesmerizing The wonderful accordionist Otto Lechner accordionistThe wonderful Lechner Otto ofThe results thismethod for speak themselves: Georg Winter, now a Principal Investigator Winter,at nowGeorg aPrincipal where a truly memorablewhere atruly anend. to event came CeMM, was critically involved critically inthe develop was CeMM, where they ultimately are destroyed and recycled. Unlike previous therapies, it attacks cancer cancer itattacks Unlike previous therapies, ­questions and continued with the discussion literally hundreds­literally of young more well as senior as protein degradation targeted ­JQ1-mediated cell’s garbage disposal center –the proteasome – disposal cell’s garbage audience of more than 400 people. After his audience of more 400people. After than ­accompanied Lecture Landsteiner the CeMM participants at the subsequent cocktail reception, reception, at the subsequentparticipants cocktail postdoctoral fellow laboratory. ­postdoctoral inthe Bradner ment of a histime thismethod as during proteins not by inactivating their individual parts, ­proteins parts, their notindividual by inactivating Jay Bradner answered the gathering’s many the answered gathering’s Jay Bradner talk, thrived like healthy, like thrived cells again. normal but by dragging them, intheir entirety, them, the to but by dragging blood cells of leukemia patients with treated ­

Ce — M­—M­— Research Report 2017 Facts Life 100 101 “Machine learning is the most powerful tool isthe most powerful learning “Machine A key feature responsible for this technology’s responsible for thistechnology’s A key feature At the AustroMetabolism workshop theAt AustroMetabolism on AustroMetabolismWorkshop Learning is Changing Everything 7th S.M.A.R.T Lecture –Machine words with which Hermann Hauser, physicistwords Hauser, withwhich Hermann vesicular trafficking of organelles, nutrients andof organelles, trafficking vesicular on commercial platforms are just some just are platforms on recent commercial of nutrient transporters, to the extracellular the to extracellular of nutrient transporters, 2016 27, on March on MachineLearning Lecture dealing with one of the fastest developing withonedealing of the fastest examples for the capabilities of machine learning. examples for of machine the learning. capabilities deciphering the complexdeciphering of interactions metabo character of classic programming, machine programming, of classic character conditions. and inflammatory incancer lism and immunity already having, on everyone’s lives. on everyone’s having, already opened S.M.A.R.T. the 7thCeMM at Cambridge, entrepreneur serial and inordinately successful CeMM to share their diverse range of expertise, of expertise, range their diverse share to at CeMM grammed rules. Overriding the deterministic the deterministic Overriding rules. grammed Speech recognition onSpeech mobile phones, face clearly illustrates inmachineprogress learning that emphasized Hauser intelligence, Hermann the –these are developed­mankind has sofar” ­recognition or programs recommender systems September 28, 2017, experts inthe fields experts of 2017, 28, ­September reactive metabolites. The talks also focused on alsofocused The talks metabolites. reactive introduce their cutting met ­metabolic regulation inhealth and disease mechanisms of withthe­mechanisms cellular interaction from big data instead of instead following big pre data from the real impact soonthe thistooland real have, is will ­technologies similar to of Incontrast our time. forms and facilitate new collaboration. During During new collaboration. and facilitate forms learns tremendous the isthat system success sounding but refuted predictions on artificial on predictions artificial butsounding refuted the workshop, explored speakers various surrounding environment, ranging from studies studies from environment, ranging ­surrounding edge technology plat technology -edge -pro ­ ­ - ­ While this new technology will offer humanity offer humanity will thisnew technology While Organized by CeMM PI Andreas Bergthaler, Bergthaler, Andreas PI by CeMM Organized world’s most prevalent diseases, such as diabetes, diabetes, such as world’s most prevalent diseases, University of Vienna, thisworkshop a as of Vienna, served University of Vienna and Thomas Scherer from the Medical the Medical from and Scherer Thomas of Vienna Hauser alsopointed intelligent outHauser the risks: Hermann Hauser gave a thrilling overview of overview athrilling gave Hauser Hermann on machine learning, lecture In hisS.M.A.R.T. data size continues size is grow, to Hauser data Hermann cancer and chronic infections. Strengthening Strengthening and chroniccancer infections. evening at CeMM! ­evening sectors. and health care inthe service ­especially convinced that machine learning will improve,convinced will machine learning that on probabilities allow that isbased learning Richard Moriggl from the Veterinary University University the Veterinary from Moriggl Richard ­Moreover, the we do way change business itwill agreed to focus on inthe future. focus to agreed broad range of innovations and advantages, of innovationsa broad range and advantages, of industries. abroad range and affect constantly are improving and and availability astonishing features of thisrevolutionary features ­astonishing improving data sharing and expanding access to to access and expanding sharing improving data evolving collaborations, internal the community, guessing andguessing decision machines might jeopardize more 50%of jeopardize might than machines more of and more our life. areas pervading technology were the were keytechnology points the experts strength of itshigh the strength the At however, time, same jobs. ontoday’s technology – a wonderful and illuminating and illuminating –awonderful ­technology developmentsthe latest and presented some opento up unique opportunities, business isexpected ­technologies, machine learning starting point for the catalysis of point astronger meta for the catalysis starting boosting the made inbattling some efforts of the withaview to inAustria bolic cluster research making. As data quality quality data As -making. -throughput and sensor ­ lively discussions. of thistechnology provoked The opportunities and risks Lecture onMarch27, 2016. Hauser at the7thS.M.A.R.T. explained by Hermann changeswaseverything How machinelearning S.M.A.R.T Lecture new ogy platforms and facilitate their cutting-edgetechnol ofrange expertise, ­ 2017, tosharetheir ­ at CeMM on September 28, health and diseasemet metabolic regulation in Experts inthe fields of AustroMetabolism a ­degradation of ­using the example medical innovations His talk onprinciplesof Lecture onMay 15, 2017. 11th CeMM Landsteiner Jay Bradner heldthe Landsteiner broad audience. ­ targeted protein ­collaboration. ­attracted introduce diverse -

Ce — M­—M­— Research Report 2017 Facts Life 102 103 “A network approach to “What youalways “Clonally transmissible “Transcription of the amna devils” ­Tasmanian The story of a shifting 15.3.2017 24.1.2017 22.3.2017 eeiay Medicine, ­Veterinary 9.3.2017 to human” University ofUniversity Vienna, United Kingdom ofUniversity Cambridge, ­wanted toknow about Austria Ulrike Felt Ulrich Stelzl genome:From yeast Department of Impromptu Department of Science Lecture Responsible Research Menche Host: Jörg BioTechMed, University Institute of Pharma­ Impromptu Andreas Host: Host: Giulio Superti-FurgaHost: Giulio Biophysical Chemistry, Max Planck Institutefor Host: Sylvia Knapp informed consentin and TechnologyStudies, Scientific Meetingsin2017 and Seminars Overview f Graz, of ceuticaland Sciences cancers indogs and Co-Host: GeorgCo-Host: Winter Göttingen, Germany CeMMinar concept and practice”concept and Elizabeth Murchison Patrick Cramer human kinasespecificity” imdcl research: ­biomedical ­Austria ­Bergthaler “Regulation of inflamma “Taking outthecell “Informing clinical “Machine learningis 10.5.2017 15.5.2017 Yury Miller School of Medicine, Smart Lecture 2.5.2017 27.3.2017 tutrl chromosome ­structural tion via selective tion via United States United States United Kingdom James Bradner Amadeus CapitalAmadeus abg wt chemical with ­garbage Metabolism, University Endocrinology and Department of Medicine, Host: Giulio Superti-FurgaHost: Giulio Medical School,Boston, HospitalHarvardand and Women’sBrigham Impromptu Binder Host: Christoph Impromptu Superti-FurgaHost: Giulio Research (NIBR) Institutes for BioMedical President of theNovartis Landsteiner Lecture Host: Kaan Boztug evolving ­Implementing ­Partners, London, ­ nepeain of ­interpretations of California SanDiego, degraders” ­cholesterol efflux” changing everything” hoai structure” ­chromatin Hermann Hauser Cynthia Morton knowledge from rearrangements:

- “An unexpectedforce “Microbes trigger “Application of peptide Tina Freisinger (ibidi), 12.6.2017 Sabine Rauscher (MUV), 20.6.2017 27. – 29.6.2017 from within: The within: from susceptible hosts” United States United States ofUniversity Chicago, (Olympus), NHLBI, NIH,Bethesda, Department of Medicine, Impromptu Binder Host: Christoph Host: Kaan Boztug Design and Pharma­ and Design Department of Drug Impromptu Elias Horn(ibidi) Marion Gröger (MUV), Loïc Dupré(LBI-RUD), in Th1 immunity” Host: Stefan Kubicek muiy and ­autoimmunity cellular critical roleof intra­ CeMMinar ­cancer ingenetically Organizers: Reinhard Hinterleitner Claudia Kemper Copenhagen, Denmark cology, University of Christoph Schön of protein interactions” Motility Workshop Immune Cell Hans MichaelMaric ­profiling andinhibition microarrays for the 28.6.2017 ­complement

“WASp caught inR-loops: “Exploiting gene discovery and “Drug “The metabolic 17.8.2017 YatinM. Vyas 3.7.2017 tde, King' ­Studies, 30.6.2017 29.8.2017 unrblte of ­vulnerabilities hrpui relevance” ­therapeutic ­transcriptional transporters” United States University of Iowa, nvriy Austria ­University, Aldrich syndrome” Division of pediatric Impromptu Loizou Host: Joanna ofDivision Cancer Host: Kaan Boztug RNA pathologies” London, United­ Basel, Switzerland BioMedical Research, Novartis Institutesfor Impromptu Innsbruck Medical CellBiology,Department Loïc Dupré Hosts: Kaan Boztug and Host: Giulio Superti-FurgaHost: Giulio instability in Wiskott- a nuclear view of discover cancer ­dependencies to CeMMinar chemical biology of yfnto ad genomic and ­dysfunction CeMMinar Francesca Ciccarelli hematology/oncology, Nicole Meisner-Kober David Teis ­regulation of nutrient College s Kingdom

“Congenital myasthenic “Image-based screening “Regeneration of Thomas Scherer (MUV) Sciences,Austria Vienna, Transcan Epimark 25.9.2017 21.9.2017 28.9.2017 26.9.2017 Vienna, Austria Vienna, 9.10.2017 Zdenko Herceg(IARC) for new chromosome syndromes, a groupof treatable hereditary ­University, Jan Senderek Workshop (VetmeduniVienna, (CeMM), Austrian Academy ofAcademyAustrian Andreas Bergthaler Biotechnology of the Institute of Molecular IMP, Research Institute MUV, LBI-CR), Richard Moriggl Host: Kaan Boztug Munich, Germany Ludwig Maximilian Friedrich Baur Institute, Impromptu Superti-FurgaHost: Giulio Host: VanjaNagy in axolotl” CeMMinar Christoph Bock (CeMM) Organizers: complex body parts of Molecular Pathology, CeMMinar Organizers: ­disorders” organizers” Daniel Gerlich Elly Tanaka Annual Meeting AustroMetabolism 2017

“Functional microbiome “Molecular mechanismof “Intestinal organoids“Intestinal as “Promenade anden 16.10.2017 25.10.2017 23.10.2017 27.9.2017 Whitehead Institutefor nvriy f Vienna, of ­University their toolsfor genetic Austria ­Alzheimer' ­Wissenschaft undKunst” (­Josephinum) (CeMM), Impromptu Superti-FurgaHost: Giulio ­Ecosystem Science, Biomedical Research, Host: Giulio Superti-FurgaHost: Giulio Host: Christoph Bock Host: Christoph irbooy and ­Microbiology Department of IMBAAustria Vienna, Koo Laboratory, Impromptu nlss with analysis Schnittstellen von Science meetsArts: action of a major Cambridge, UnitedStates resolution” risk factor” a model system and CeMMinar Christiane Druml Giulio Superti-Furga Organizers: Michael Wagner Bon-Kyoung Koo ­manipulation” Greg Sienski disease s

­single-cell "Alpha shapes “Chemical physiology of “The roleof maternal “ 17.11.2017 13.11.2017 27.11.2017 ina Austria ­Vienna, United University of Cambridge, (FHchol Austria) (CeMM, MUW) 8.11.2017 loihs Geometry ­Algorithms, Host: Jörg Menche Host: Jörg IST Austria Department of Impromptu Research Focus Edelsbrunner Group, Impromptu Superti-FurgaHost: Giulio Host: VanjaNagy Medical University Neuropharmacology, and ­Neurophysiology Department of Impromptu in neuropsychiatric activationimmune and beyond" and Topology, ­Chemistry, Gabriele Hanauer-Mader Christoph Binder Organizers: ­disorders” FH Symposium: Herbert Edelsbrunner Daniela D. Pollak natural products” conjugatesprotein and unterschätzte lesterinämie –eine Goncalo Bernardes genetische Erkrankung” aiir Hypercho- ­Familiäre ­Kingdom

“RNAevolution: virus “Expanding the “Incorporatingsex and 15.12.2017 28.11.2017 your research” 4.12.17 United States ofUniversity California, nvriy Medical ­University United States genderinto aspects ­Immunology, and ­Microbiology Department of Ligandtargetand Primary and TransmuralPrimary Professor of Gender in Lecture Responsible Research Andreas Host: Superti-FurgaHost: Giulio California, La Jolla, Research Institute, Scripps Medicine, The Department of Molecular Impromptu Sabine Oertelt-Prigione Host: Sylvia Knapp CeMMinar ­discovery by fragment- proteome: ­druggable etr Te Netherlands The ­Center, Care, Radboud during infection” ­consequences Raul Andino based screeningincells” Christopher Parker mechanisms and mechanisms

­Bergthaler

Ce — M­—M­— Research Report 2017 Facts Life 104 105 enhanced by alumni long after they leave CeMM. byenhanced alumnilong after astrong itbuilds events, numerous ­ other social for the whole or party family the yearly the festive outing, Christmas Like at CeMM. one just their beginning studies monthHalloween Party, after anannual students organize theiryear, first thePh.D. During spirit. CeMM events play role animportant social whenOur the itcomes maintaining to cooperation and day research, ­successful inexecuting advantage aclear 43nations as from of members our team backgrounds cultural publications. We and different celebrate the diversity groups innearly research CeMM allof of our members different between inco isalsoreflected Spirit” “CeMM and This collaboration. ­hierarchy and anopen We aflat cultivate and familiarity. trust nurtures that climate our social developed has aworkingCeMM mode of super Events Social at Vienna’s City Hall. Viennese ­ and textbook exampleof the scientific community this annual highlightfor dancing skills. Once again, CeMMies showedtheir Ball on January 27, 2017, At the3rd Vienna Science Vienna ScienceBall culture took place -door foster level ahigh that policy of networking -to day business. -day cooperation based on -cooperation based community that isalso that community -authorships on September 26. in the Vienna NightRun of them also participated 2017 - a new record!Many ­Marathon on April 23, teams ran the Vienna City social life. 19 CeMM ofimportantaspect CeMM ' Doing sportstogether is an and Night Run Vienna CityMarathon s to Austria. ­Islam and itsrelationship the historical roleof about talk ­eye-opening Bert Fragner held an Austria. Professor Emeritus beautiful sightsof Lower Schallaburgtwo Castle, us to Göttweig Abbey and our On September 29, 2017, CeMM Outing annual excursiontook

Ce — M­—M­— Research Report 2017 Facts Life 106 107 and group ­ with priceless­ new pinnacleof creativity ­CeMMturies" resultedin a the "­ On ­ the Halloweenparty. students was to­ duty of thenew Ph.D.­ Like every year, the first Halloween Party October 25, 2017, journey throughthe costumes. disguises organize party onDecember 18, 2017. organizedthe Christmas second year Ph.D. students, the holiday season. The put all the CeMMies into delightful dancingmusic gifts for thechildren and faculty, a bagfullof Santa' sketches performedby the including improvised A fabulous stage show Christmas Party s

Ce — M­—M­— Research Report 2017 Facts Life 108 109 societal and ­ ­societal scientific, and of its extraordinary CeMM years ­celebrated ten into Until late the laughed people night andinspired. danced, the audience left delighted and features and many other special ­ astonishing wishes, delights, heartwarming ­musical guests of andlight highlights, videohonor, scientific shows, of overwhelming mixture Awonderful in 2010. building research and memorable event since the opening of our ­spectacular most biggest, CeMM’s was at the Aulader Wissenschaften 2017 celebration 12, on September anniversary The 10th 10 Years of CeMM achievements. cultural theater theater

Ce — M­—M­— Research Report 2017 Facts Life 110 111 ­winners in12 ­ ­audience Book Challenge and " exhibition of the"Blue ­evening began with the The Wissenschaften. ­jubilee in the Aula der celebrated CeMM' More than400 guests ­voting categories. o the for s the

molecular interactions. depicts whole setsof showed how their interface Jörg Menche’s group the BlueBook exhibition. demonstrated duringthe reality wasin virtual Big datavisualization

Ce — M­—M­— Research Report 2017 Facts Life 112 113 over theentirefestivehall. blowing visual effects all digitally mapped mind- art collective Lichttapete ­ranking while thelight on CeMM' held thekeynote speech Jo Bury, director of the VIB, s international s

a short theatrical piece. ­excellent acting skillsin demonstrated their evening. Onstage, they the guests through guided and ­embodied the characters they fields of research with introduced CeMM' Kainz of Businesstheater, Wolfgang by ­directed Open with membersof the The Walking Acts, House Theatre s main s

Ce — M­—M­— Research Report 2017 Facts Life 114 115 during thecelebration. the musical framework provided Alma ensemble instrumentalfunding. The importance of research ­playfully highlightthe and ­ Thomas Henzinger, Müller,Tockner,Klement Helga Nowotny, Markus Andreas Mailath-Pokorny, by MartinModer, brought making quiz, moderated The CeMMmoney-­ Jo Bury onstage to a time-capsule look. ­delicacy, custom-madein less than a 10-layer could hardly settlefor of theoccasion, we cake.a needs Tobe worthy every proper celebration that agree we sure I'm Did wementionthecake?

Ce — M­—M­— Research Report 2017 Facts Life 116 117 award ceremony. in an announced were of theBlueBook Challenge Subsequently,the winners official celebration act. by theguests after the enjoyed and drinkswere Conversations, snacks

crowd tothedancefloor. Augustin luredtheparty DJaneand Alexandra band The DublinLegends The world-famous Irishfolk as theeveninggot late. were a commonsymptom Blistered dancingfeet

Ce — M­—M­— Research Report 2017 Facts Life 118 119 However, the members of CeMM are also aware of their responsibility ­However, of their alsoaware the are of responsibility members CeMM CeMM is in many respects an unusual institution withambitious institution anunusual isinmany respects CeMM its publications and grants, by its ability to train young researchers, young train researchers, to its publications by itsability and grants, of and originality by the quality itsperformance measures institute long Cmuiy Service Community The ERC is governed by the Scientific Council, TheCouncil, ERC by isgoverned the Scientific towards taxpayers which requires an open dialogue with society and which withsociety anopen dialogue requires taxpayers towards and potential to therapeutic innovation. diagnostic speak that The ERC Scientific Council acts on behalf acts of Council The ERC Scientific CeMM Director Giulio Superti Director CeMM Council since 2014. From 2010 to 2013 Professor 2013 to 2010 From since 2014. Council as well as by successfully carrying out projects with a medical impact out projects withamedical carrying by well successfully as as In 2017, on the 10th anniversary of its existence, of itsexistence, on the anniversary In 2017, 10th Helga Nowotny,Helga Professor of aViennese Social conducted inanyconducted field ­ conducted consisting of eminent scientists European ensuring that politicians protect and promote protect politicians that ensuring has been President been ofhas the Research European creativity and innovative research. Giulio and innovative research. ­creativity European Union. Excellence­European isthe sole ­ isthe most and important Council Research ­Council (ERC) engagement in community projects. Some examples projects. incommunity of community engagement Bourguignon, a renowned French mathematician, a renownedBourguignon, mathematician, French Professor Jean Commission. ­European nominated are by­Members anindependent Europe by promoting excellence and inresearch appointed Member of the Scientific Council appointedof Council of Member the Scientific Scientific CounciloftheEuropean Research scholars including Nobel Prize laureates. laureates. and Nobel scholars including Prize basic research for institution research basic prestigious funding service performed by CeMM and by its ­ CeMM performed service She was alsoafounding member of theShe ERC was held of thisprestigious Science position. Studies nor or for other geographical funding. quotas 2007. in 2007. more and innovation science ­Superti for selection; there neither are ­ European The European the ERC of 4years. for aterm ERC as the most successful research funding funding the research ERC the most as successful Europeto in community thepromote scientific search committee andsearch appointed by the scheme of the EU. Results from basic research research basic from scheme Results of the EU. term goals in reshaping the medical research landscape. The landscape. research goals inreshaping the medical -term Furga’s aspiration is to contribute isto a to aspiration -Furga’s friendly climate in climate -friendly thematic priorities, thematic priorities, Furga has been been has -Furga within the Pierre -Pierre criterion criterion qualifying volunteers the opportunity to to volunteers the opportunity 20 qualifying Genomes.org foundation. Genom Austria foundation. Genom Austria Genomes.org Genome Project, Genom Austria provided Genom Austria Genome Project, as a scientific conference. An outstanding An outstanding conference. ascientific well as workshops, teacher trainings and­workshops, afilm work trainings teacher young people. To these goals school high reach Sciences, and organized public debates as and organized of Sciences, In 2014 “Genom Austria” was announced as was “Genom Austria” In 2014 developments implications. and associated and inthe inpublic media ­education, debate. educational, philosophical, ethical, and social and social philosophical, ethical, ­educational, been initiated to explore the scientific, explore to initiated been thehas scientific, Following the model of Harvard’s Personal Following Personal the model of Harvard’s European Researchers’ Night Nights and Long Researchers’ European Genom Austria, aScientific, Cultural and Medical University of Vienna, and the Personal of Vienna, University ­Medical accompany and step should therefore at every us also for the industry. European and a motor for innovation and competitiveness, joint Citizen Science Project of CeMM, the of Project CeMM, Science a joint Citizen and to contribute to the genomic literacy of as ofand as contribute to the to genomic literacy Society and to politics must have the courage Society Superti keepinvest to pace withscientific innew projects, 2017/beginning of 2018. of 2018. in 2017/beginning implications genome of personal sequencing. many Austrians as possible, particularly particularly possible, as many Austrians withwhole genome associated information risks ­Educational Project pilot phase of Genom Austria whichthe ended of pilot Genom phase Austria biology, from ethics, of experts team medicine, to start apublic debate and on start theto opportunities aimwas withthe Animportant public. the data stood as a fundamental component afundamental stood of as our future sociology and other accompanied disciplines ­sociology shop were offered, CeMM participated at the participated shop CeMM offered, were genomessequence their personal and share to become a core theme of everyday life –in become life acore theme of everyday members include:members Furga’s aim is for science to beunder to aimisfor science -Furga’s ­ ­ ­ + + + + + Together withthe EU The Genom Austria team would team recommendThe to Genom Austria representation of the Austrian population representation ofThis the Austrian age, origin, education, socioeconomic status socioeconomic education, status origin, age, (e.g. Genom Austria, please visit the project websites. visitthe please project websites. ­Genom Austria, would require financial and political support. In and politicalwould support. financial require Undoubtedly, the potential genome has research www.eu-life.eu/tags/publication on genome level berelevant inmedical will www.genomaustria.at www.genomaustria.at ­decision develop could comprise personal the database data, complex questions, thereby contributing to join to we decided forces address to ­landscape, highly competitive research international height, weight and biometric features) informa weight and biometricheight, features) could besequenced anAustrian assemble to During difficult economic times and withina difficult During For more on the information of pilot phase and personal history) and (gender, phenotypic history) and personal Inaddition genomic to ­applications and studies. pushing Austrian and European science forward. forward. and science European Austrian pushing genome. reference an Austrian i.e. support for create to step, politicians the next hundredmeantime, volunteers several declared is therefore involve to and important citizens on of amultitude questions. scientific research which project, abroader research now start reference genome from healthy individuals. genome­reference healthy from individuals. ­position have published been papers during several science, inthe life centers research Working GroupsandPosition Papers for major influences business on society, their interest. Itisnow uptheir stakeholders to interest. and tion provide to for the interdisciplinary basis the genomes of 5years, Austrians the 1000 next last years: the last successful and raised high attention high and raised and inthe ­successful Thesamples. of pilot the phase project was Statement on protectionStatement of used animals On the conceptOn of Innovation anEuropean Statement on the 10th Anniversary of the on theAnniversary Statement 10th Key elementsKey for excellence inresearch: EU Council European Research Council (ERC) Council Research European Programme FP9: The next Horizon – Strategies –Strategies Horizon FP9: The next ­Programme a contribution EU from ­innovation for purposes scientific to promoteto competitiveness European in LIFE’s vision for European -LIFE’s the next ments, and the health care systems. It systems. ­ments, and the health care makers beyond-makers the simple donation of LIFE alliance of alliance 13top -LIFE -LIFE ­ Academy of Sciences and its sister institute and institute itssister Academy of Sciences ME_00010/index.shtml ME_00010/index.shtml CeMM Administrative Director Anita Ender Anita Director Administrative CeMM comply to who around fail the withnew rules of society can bestored and made available can of society protection law.of the new data They have also www.parlament.gv.at/PAKT/VHG/XXVI/ME/ published to andIMBA statements submitted In May 2018, the Data Protection Act (DPA) Act Protection will the Data In May 2018, data andwhich results have and been which data are of an protection right The data documentation. consisting of universities, research institutions institutions research consisting of universities, Ministry for Education, Science and Research and Research Science for Education, Ministry Regulation (GDPR), a framework with greater withgreater aframework Regulation (GDPR), utmost importance to make sure that research utmost research make that to sure importance develop to organizations special and funding generated with public funding and the to withpublic benefit generated funding research initiatives or initiatives purposes. documentation research shouldindividual not but belimited itisof and regulations and for research rules science through so through the ­ together with the legal department of the Austrian together department withthe of legal the Austrian storage and handling of personal data. and data. handling of personal storage scope and much tougher punishments for those been active inaworking active been group by the initiated be replaced by the EU’s General Data Protection Protection Data General be replaced by the EU’s Austrian Parliament on Parliament the implementationAustrian called “broad consent” for “broad other-called

Ce — M­—M­— Research Report 2017 Facts Life 120 121 Peter Kogler. CeMMtogether artist with art, visited and science operates at theinterface of the ERESfoundation, which the executivecommitteeof Sabine Adler, member of On September12,2017, piece ofpiece art! grateful for his wonderful BrainLounge. Wevery are contribution tothe CeMM ­Kupelwieser deliveredhis the renowned artist Hans On February 28,2017, a wonderful event. curator MoritzStipsicz for and the Josephinum of Christiane Druml,Director We would like tothank CeMM. and ­Josephinum a joint eventof the and scientiststoppedof creativityon artists among restriction and ­oppression on theinfluenceof a Brain Lounge discussion On September27, 2017, “opening closed for doors” the benefit of ­ “Science + Art = Future”. This formula was part part was formula This =Future”. +Art “Science Among the factors critical to innovative science at CeMM are are at CeMM innovative to science critical Among the factors distinguished artist alsocontributed the to The artist distinguished who to withrooms helped dedicated the enhance to building valued CeMM’s interest for and understanding of interest for CeMM’s andvalued understanding Over the last coupleOver the last since of itsinauguration years On September 12, 2017, Sabine Adler visited Adler Sabine visited 2017, 12, September On (since 2012) and the Time Capsule (since 2015). In 2017, the Brain the Brain In2017, and (since 2015). the Capsule Time (since 2012) Brain Lounge and he Lounge isamentorBrain and special Munich, Germany,Munich, the non Dr. Adler Sabine isamember of the executive Lounge was enriched by a wonderful work by by awonderful enriched created of art was Lounge faculty and scientists at CeMM as well as with well as as and at CeMM scientists faculty proved to has Lounge Brain the CeMM in 2012, responsible for not only façade. the CeMM the discussion of questions, (scientific) where the discussion CeMM together with Peter Kogler, together withPeter CeMM who is and by guests at our left discussion ­messages thinking rounds in the CeMM Brain Lounge. Lounge. roundsthinking Brain inthe CeMM be an incubator for fruitful interchange among interchange forbe anincubator fruitful Sabine Adler seized the opportunity to talk to to talk to the opportunity AdlerSabine seized interaction. We are also immensely grateful to affiliated artists, artists, We affiliated to ­interaction. alsoimmensely are grateful renowned artist Hans Kupelwieser.renowned Hans artist and and independence creativity well as as ­internationality ­free and artists. At n Science and Art a mono and itsrole sees about in“helping bring to guestbook inwhicha dedicated we collect guests from all imaginable disciplines. allimaginable guests from operates at the interface of art and science and science of art at the interface operates inour, Logbook Adler Sabine left of the message contact person for person out ­contact consilience” inthese too ­consilience” in foundation. Located committee of the ERES several group leaders at CeMM, followed group at CeMM, by leaders a several disciplinary approach not might besufficient. disciplinary discussion withGiulio much and Peter.She very ­discussion brainstorming and visionary thinking: the CeMM Brain Lounge Lounge Brain the CeMM thinking: and visionary ­brainstorming designed our labs and offices to be full andof light designed space and for our officesto be scientific labs mindedness. We are very grateful to architect Kopper, who architect to We-mindedness. grateful very are disciplinary and even a scientific and ascientific even multi­ -disciplinary -of often distinct worlds. distinct -often -the profit organization -profit organization -box and thinking scientists scientists complementedWitt collection of the historical The Bridge to Survival” illustrated Vienna’s Vienna’s illustrated Survival” to The Bridge topped off ajointThe discussion event hosted visitors into unexpected audiovisual spheres audiovisual intovisitors unexpected A special highlight of 2017 was a discussion that that adiscussion was of highlight 2017 A special University of Vienna on the occasion of on of the an occasion Vienna University Standard, and MedUni Vienna Professor and MedUni Vienna Standard, Der Michael Trauner.Michael ­pioneering role inthe development of artificial Hubert artist contemporary were participants increasing isolationismincreasing and nationalism on art it provided a forum for leading journalists, artists, artists, it provided journalists, for leading aforum instruments and anatomical wax models wax and­instruments anatomical and interventions achievements. Inaddition, research of extraordinary decades and the preceding hearts needs and financial importantly, they discussed and of the of forming resistance mainspring took placeroom of inthissingular on the effects the Sao Paulo Biennale, Oscar Bronner, Oscar founder Biennale, Paulo the Sao at the including Venicethe 1980s Biennale and opposeto and provoke. Among the discussing by artists Judith Fegerl, Peter Garmusch, Garmusch, Peter Fegerl, Judith by artists andby the CeMM Josephinum of the Medical Stephanie Pflaum, Samuel Schaab and Anna Samuel Schaab ­Stephanie Pflaum, since internationally exhibited whoScheibl, has and science. Moderated by Giulio Moderated Superti and science. artists and scientists. They enlarged upon They enlarged the and scientists. artists blurring the lines between art and science. art the lines between and blurring of among oppression on creativity and restriction of Trend the journals and Profil and editor of opposition the well and influence as as of art ­exhibition at the – Josephinum: “ArtificialHearts created an extraordinary experience, taking the taking experience, anextraordinary ­created scientists andscientists debate physicians to the influence science on society and economy. on society ­science Finally, yet dependencies and how they influence theability Furga, -Furga,

Ce — M­—M­— Research Report 2017 Facts Life 122 123 Visits to CeMM Visits We are very proud that, over the years, CeMM has been honored been has CeMM by overWe the proud years, that, very are visits from many dignitaries and key decision many dignitaries visits from For CeMM, openness and accountability are an inherent attitude. aninherent are attitude. openness and accountability For CeMM, aims to betheIt aims to antithesis constantly Being of the tower”. “ivory On October 3, 2017, CeMM had the had honor CeMM 2017, and 3, October On science. for science. but alsoambassadors anda center for research, training we consider society, to ourselves not of ouraware responsibility only of honor. We grate filled are and with pride very – spirit” –the members of “CeMM allCeMM of our on of the theanniversary occasion 10th Alexander Van and der Bellen, theof Austria, our dialogue withsociety. our dialogue constant support over many years. We supportconstant over many years. now feel Mayor of the City of Vienna, Michael Häupl, Michael ofMayor Vienna, of the City Mayor Häupl Michael for their visitand their and MayorMichaelHäupl needs as well as the enthusiasm and the well ­ enthusiasm needs as as and pur to impact on of the the medicine future The ambition an create to of CeMM ­institute. President host the to as Federal ofpleasure acting perform the best medical research and to research the medical best perform andmore to motivated ever than encouraged ful to President to Alexander Vanful der Bellen and President Alexandervan derBellen sue basic research that is focused on patient isfocused that research sue basic seem to have to seem made animpression on our guests persistence persistence ­continue ­ ­ On May 10, 2017, acelebration marked 2017, May 10, inVienna On ­welcome the ERC President Brain at the CeMM had CeMM (ERC). thisoccasion, On Council of – and continue for and will –frontier science to Lounge and to engage in a discussion round with inadiscussion and engage to Lounge ­Jean Scientific Council, Giulio Superti Council, ERC Scientific ERC and CeMM young grantees from scientists and befriended institutes. As member of the As institutes. and befriended Visit ofJeanPierreBourguignon institutions inAustria. institutions foster active dialogue with scientists and withscientists host dialogue foster active the to celebration privilege agreat day. Itwas host ERC to as the of pleasure President acting of the Research European the anniversary 10th the honorable mission of aspokesperson being Pierre Bourguignon on the of morning -Pierre -makers. Furga has has -Furga the entire staff of CeMM. Ender and cheeredby Superti-FurgaAnitaand CeMM ­ CeMM, visited Häupl ­Michael of the City of Vienna, der ­Austria, ­Federal President of On October3, 2017, Bellen, and theMayor Directors Giulio ecmd by ­welcomed lxne Van ­Alexander the CeMM Brain Lounge. affiliated institutes at and CeMM from ­scientists granteesyoung and Furga, he also metERC Hosted by GiulioSuperti- CeMM on May 10, 2017. Jean PierreBourguignon to to welcome ERC President It wasagreatprivilege

Ce — M­—M­— Research Report 2017 Facts Life 124 125 Awards The following awards are illustrative ofThe following the CeMM many successes illustrative are awards At theAt ceremony, President der Bellen van ­Alexander Van der Bellen awarded the promotio On December 19, 2017, Austrian president Austrian 2017, 19, December On Oxford (December 2014), yet enrolled remained 2014), Oxford (December had the pleasure of celebrating in 2017. CeMM is very proud of isvery its CeMM the ofhad pleasure celebrating in2017. The ISCB’s announcement Overton The ISCB’s of the 2017 these prestigious awards! Giulio Superti with distinction in molecular biology (Mag. rer. biology (Mag. inmolecular with distinction CeMM until Sebastian Nijman’s lab moved lab Nijman’s to Sebastian until CeMM 2017 ISCBOvertonPrize:ChristophBock In 2011, she applied position at CeMM forIn 2011, aPh.D. In 2017, CeMM PI Christoph Bock received the received Bock Christoph PI CeMM In 2017, epigenetic data analysis”. ­epigenetic data expressed hisadmiration forexpressed the and endurance of Barbara Mair having earned top grades at school, high all top grades having earned the exceptional and intelligence talent curiosity, ­completed withanexcellent her thesis Ph.D. withambition, paired intellect diligence, ­critical Prize award recognizes the computational recognizes award Prize Mair, former Ph.D. student at CeMM. To at CeMM. student qualify Mair, Ph.D. former and linguistics (BA). During her Ph.D. studies, studies, her Ph.D. and During (BA). linguistics exemplary moral character. an exemplary and an impressive public defense of her work. She of Vienna. University at the Medical Society for Computational Biology (ISCB) for for Computational Biology (ISCB) Society nat. equivalent to MSc) and in Spanish literature and inSpanish literature equivalent MSc) to nat. start. the very madeimpression from had Barbara achievements. for such outstanding necessary prestigious prize awarded by the International prestigious prize at stayed and work. Barbara hard ­perseverance successful members and graduates. Congratulations on winning Congratulations and members graduates. successful for the honor, meet to isrequired anindividual throughout her undergraduate years and grades and grades throughout years her undergraduate the highest of academic standards andthe have to highest of standards academic Promotio subauspiciispraesidentis she continued and impress to withher sharp significant contributionssignificant to computational sub auspiciis praesidentis rei publicae to Barbara praesidentis publicaesub auspiciis rei Barbara to biologist Christoph Bock as “a rising star in star ­biologist “a rising as Bock Christoph biology through research, teaching and service. and service. teaching ­biology research, through Furga emphasized the stellar emphasized -Furga

Academy of Sciences in2013. Academy of Sciences On June 7,On Giulio 2017, Superti The order was given byThe of order decree the President was Title ofCommandertheOrderMerit (Order of Merit of the Italian Republic) of by the of(Order HE Italian Merit Giorgio Marrapodi, Ambassador of Ambassador Italy. Giorgio Marrapodi, Christoph has dedicated his career to under to hiscareer dedicated has Christoph on epigenetic biomarker development helped has the Italian Republic Sergio Mattarella who Republic Mattarella of Sergio the Italian Institute for Informatics (2004) and conducted (2004) for Informatics Institute developedHe pioneering methods and software Italian president, the importance of science in of the president, science importance ­Italian Investigator at CeMM and­Investigator professor avisiting at CeMM at data during his Ph.D. studies at Planck the Max studies hisPh.D. during data economy, philanthropic and social, public service, della Repubblica Italiana dell‘Ordine alMerito epigenome projectand Human the International large companions, and friends. family in ­ceremony Embassy took place at the Italian leadershipThe and achievements. scientific Ambassador Inhis moving speech, careers. and military incivilian service ­conspicuous visited CeMM together with former Austrian together Austrian withformer CeMM visited had Palais Metternich inthe presence of colleagues, Metternich Palais Republic and acquired isawarded for “merit Epigenome Consortium. Christoph Bock Bock Christoph Epigenome Consortium. Marrapodi emphasized the lasting positive the lasting emphasized ­Marrapodi is the highest ­Merit hisfirst official during Fischer President Heinz New Frontier Group award from the Austrian FrontierNew Group the Austrian from award postdoctoral fellow at the Broad Institute. fellowa postdoctoral at the Broad Institute. and humanitarian activities and for activities long and and humanitarian ­awarded the title of Commendatore (Commander) general and thegeneral impact of Giulio Superti 2012, Christoph Bock has been a Principal aPrincipal been has Bock Christoph Since 2012, impression made on visithad the the CeMM personalized medicine. He has also been one alsobeen of has He medicine. personalized received an ERC Starting Grant in 2015 and a in2015 Grant anERCreceived Starting for analyzing and interpreting DNA methylation DNA and interpreting for analyzing the lead bioinformaticians in the BLUEPRINT inthe BLUEPRINT the bioinformaticians lead of epigenetics value for the practical establish to research His of Vienna. University the Medical Italian Republic awardedtoGiulioSuperti-Furga standing epigenetics and the humanstanding epigenome. state visit to Austria in 2015. The of Order in2015. Austria visitto state the nation” in the fields of literature, the arts, by the the arts, nation” inthe fields of literature, scale epigenome-scale of cells stem analyses as ranking honor-ranking of the Italian Furga was was -Furga Furga’s -Furga’s ­ Superti-Furga on June 2017. Scientific Director Giulio was awarded to CeMM the Italian Republic the OrderofMerit The titleofCommander Van der Bellen. Dr.president Alexander ­presence of the Austrian Ph.D. officially awarded in ­Barbara Mair got her former Ph.D. student December 19, 2017, CeMM’s to the 17thcentury. On in Austria and dates back academic achievements is the highesthonor for praesidentis ­auspiciis The promotionsub

2017. was celebrated on July 14, to CeMM-PIBock Christoph The OvertonPrize awarded

Ce — M­—M­— Research Report 2017 Facts Life 126 127 CeMM Facts Facts Co-Workers Turkey, United States Taiwan, Ukraine, Thailand, Serbia, Slovakia, Arabia, Saudi Russia, Romania, Republic of the Congo, Netherlands, Portugal, Poland, Mexico, Macedonia, Latvia, Cambodia, Japan, Jordan, Italy, Israel, Ireland, Indonesia, India, Hungary, Croatia, Greece, Britain, Great Finland, France, Spain, Algeria, Germany, Republic, Czech Cyprus, Switzerland, China, Canada, Bulgaria, Belgium, Australia, Austria, 43 Nationalities

Ce — M­—M­— Research Report 2017 Facts 130 131 Ce — M­—M­— Research Report 2017 Facts 132 133 Ce — M­—M­— Research Report 2017 Facts 134 135 Keiryn Bennett* Senior Researcher Diseases for Rare and Undiagnosed Ludwig BoltzmannInstitute Vanja Nagy Institute CancerNetherlands Thijn Brummelkamp und UndiagnosedDiseases CeRUD Vienna Center for Rare Diseases for Rare and Undiagnosed Ludwig BoltzmannInstitute Kaan Boztug and Dentistry School of Medicine Medical Center University of Rochester KateAckerman Principal Investigators Adjunct Deputy Headfor Metabolomics Kristaps Klavins Metabolomics Facility Head of theProteomics and André Müller Chemical Biology (PLACEBO) Head of Platform Austria for Stefan Kubicek Sequencing Facility (BSF) Head of Biomedical Christoph Bock Facility Heads Georg Winter Giulio Superti-Furga Jörg Menche Joanna Loizou Stefan Kubicek Robert Kralovics Sylvia Knapp Christoph Bock Christoph Binder Andreas Bergthaler Principal Investigators Director of Medical Affairs Sylvia Knapp Administrative Director, CEO Anita Ender Scientific Director, CEO Giulio Superti-Furga Management Directory

ERC GAMEOFGATES Manuele Rebsamen ALTF 733-2016 EMBO Long-Term Fellowship Tea Pemovska BI SLC Konstantinos Papakostas Medical University of Vienna Nikolina Papac-Milicevic Medical University of Vienna Yael Nossent FWF P30041 Harini Nivarthi LBI-RUD David Medgyesi ERC GAMEOFGATES Kai-Chun Li ÖAW New Frontier 2014 FWF I1626, Thomas Krausgruber MSCA SLIM Nikolaus Krall LBI-RUD Artem Kalinichenko FWF P29018 Roland Jäger ERC GAMEOFGATES Alvaro Ingles-Prieto Eva Hug* ERC IMMUNOCORE, LBI-RUD Birgit Höger* BI SLC Leonhard Heinz ERC GAMEOFGATES Mari Hashimoto Florian Halbritter DFG Fellowship Florian Halbritter ÖAW New Frontier 2014 Michaela Gruber MSCA DRUGSUP, FWFP29250 Enrico Girardi ÖAW New Frontier 2014 Nikolaus Fortelny FWF I2798 FWF I1626, FWFF6102, ÖAW Innovationsfonds, Matthias Farlik-Födinger ALTF 245-2017 EMBO Long-Term Fellowship Ruth Eichner ERC GAMEOFGATES Ariel Bensimon University Vienna Medical Taras Afonyushkin Postdoctoral Fellows

Medical University of Vienna Clara Jana LuiBusch#* VRG15-005 WWTF Pisanu Buphamalai WF P30271 Matthias Brand CDG Laboratory Bernhard Karl Boidol LBI-RUD Jana Block FWF F4711 WolfgangJohannes Bigenzahn ERC IMMUNOCORE Hatoon Baazim ÖAW DOC Fellowship 24486 Rico Ardy Daniel Andergassen* W1212 FWF AgererBenedikt FWF F4702 SaradaNaga Achyutuni Ph.D. Students ALTF 31-2016 EMBO Long-Term Fellowship Melania Zauri* FWF M1809 KatharinaWillmann* Medical University of Vienna Stefanie Widder J3578FWF Wolfgang Warsch ERC CHEMOS AWSCHEMOS,PreSeed Ian Vladimer Gregory ERC CMIL, FWFP30047 Bojan Vilagos FWF P29555 Georgia Velimezi Medical University of Vienna Dimitris Tsiantoulas* Medical University of Vienna Philipp Starkl WWTF LS16-060 Celine Sin FWF I2192 Vitaly Sedlyarov 3-PDF-2014-206-A-N JDRF Postdoc Fellowship Sara Sdelci Michael Schuster Christian Schönauer* FWF I1626, FWFI1575 Christian Schmidl* CDG Laboratory Sandra Schick LBI-RUD Elisabeth Salzer

ERC GAMEOFGATES W1205,FWF Anna Moskovskich FWF P29555 Martin Moder* FWF P29763 Abdelghani Mazouzi#* Medical University of Vienna Rui Martins#* CDG Laboratory Brenda MarquinaSanchez ERC CMIL Alexander Lercher LBI-RUD Tomislav Kokotovic FWF I1575 Johanna Klughammer Medical University of Vienna Mate Kiss Kseniya Khamina FWF F4711 Felix Kartnig FWF F4702 Ruochen Jia BIF Ph.D. Fellowship JägerMartin LBI-RUD Jakob Huemer Alexander Hanzl Joel Hancock Medical University of Vienna Anna-Dorothea Gorki FWF P29763 Joana Ferreira Da Silva LBI-RUD Christopher Fell Astrid Fauster#* Patrick Essletzbichler W1205 FWF Eray Esendir* JDRF 2-SRA-2017-416-S-B Lennart Enders ERC IMMUNOCORE ÖNB JF16385, CeciliaDominguez Conde FWF I1626 Paul Datlinger FWF I2192 Adrián CesarRazquin JDRF 3-SRA-2015-Q-R Tamara Casteels Michael Caldera

LBI-RUD Fangwen Zhao Medical University of Vienna Sophie Zahalka ÖAW DOC Fellowship 24206 Juliane Weißer Medical University of Vienna WatzenböckMartin VRG15-005 WWTF Loan Vulliard ERC Epigenome Programming Peter Traxler ÖAW DOC Fellowship 24813 Mark Smyth Cancer Research Ludwig BoltzmannInstitute Anna Skucha LBI-RUD Tala Shahin ERC IMMUNOCORE, LBI-RUD Nina Serwas#* FWF F4702 Fiorella Schischlik Sejla Salic BIF Ph.D. Fellowship Lydia Robinson-Garcia ÖAW New Frontier 2014 André Rendeiro University Vienna Medical Federica Quattrone Medical University of Vienna Florian Puhm Medical University of Vienna Florentina Porsch FWF I2250, LBI-RUD Julia Pazmandi ÖAW DOC Fellowship 24721 FWF F5402, Robert Pazdzior FWF P29763 Michel Owusu Medical University of Vienna Georg Obermayer Medical University of Vienna Marini Ng

ERC IMMUNOCORE Jasmin Dmytrus BSF Technologist Charles Dietz* Sneha Datta* ERC GAMEOFGATES Manuela Bruckner FWF F4702 Edith Bogner Thorina Boenke FWF P30271 Sophie Bauer Data Scientist Daniele Barreca BSF Technologist Donat Alpar Computer Scientists Technical Assistantsand ÖAW New Frontier 2014 EU BERG, Lion Felix Konstantin Uhl* LBI-RUD Loic Dupre Guest Scientists YoussefMarkus Medical University of wVienna Streef Jan Thomas Medical University of Vienna Daniel Roden FWF P30047 Theresa Pinter Michael Moschinger FWF P30041 Nevena Milosavljevic LBI-RUD Nina Mair* FWF F4702 Leon Kutzner FFG FEMtech864423 Isabel Kaltenbrunner FWF P29018 Lukas Hofer* CDG Laboratory Melanie Hinkel* Medical University of Vienna Stefanie Haslinger-Hutter Chorn* Someth Peter Bannauer* Medical University of Vienna Mirlinda Ademi Diploma Students

WWTF VRG15-005 WWTF Data Scientist Felix Müller Data Scientist Heiko Müller WWTF LS16-034 Noémi Meszaros Data Scientist Peter Májek AWSChemos PreSeed Data Scientist Oscar Lopez delaFuente* WWTF LS16-034 Sabrina Lindinger LBI-RUD Ewelina Lenartowicz Medical University of Vienna Karin Lakovits ÖAW Innovationsfonds FWF I1575, Amelie Kuchler Medical University of Vienna Ana Krolo Medical University of Vienna Vesna Krajina Kosack Lindsay James FWF P29250 Justyna Konecka* Medical University of Vienna Heredia Raúl Jimenez Marie Huber* FWF P30041 Raimund Holly CDG Laboratory Gerald Hofstätter Medical University of Vienna Anastasiya Hladik ERC IMMUNOCORE TatjanaHirschmugl* Therese ÖAW New Frontier 2014 Johanna Hadler* Bettina Gürtl FWF F4702 Beatrice Grabner* ERC GAMEOFGATES Data Scientist Ulrich Goldmann Medical University of Vienna Laura Göderle ERC IMMUNOCORE Wojciech Garncarz FWF P29018 Elisabeth Fuchs Frederic Fontaine FWF P29250 Giuseppe Fiume Noel Fitzgerald Data Scientist Bekir Ergüner

Genom Austria Genom AssistantProject Elisabeth Simböck Head of Genom Austria Christine Mannhalter Austria TeamGenom ERC IMMUNOCORE ÖNB JF16385, Petronczki Özlem Yüce CDG Laboratory Wanhui You EricaSongci* Xu Marc Wiedner Jakob Weinzierl BI SLC Adrijana Stefanovic Ismet Srndic Martin Senekowitsch ERC GAMEOFGATES Stefania Scorzoni ERC EpigenomeProgramming FWF I1626, FWFI1575, Linda Schuster ERC CHEMOS AWSCHEMOS,PreSeed Monika Sabler* Kathrin Runggatscher Anna Ringler LBI-RUD Christina Rashkova ERC CMIL Data Scientist Alexandra-Mariela Popa VRG15-005 WWTF Graphic Designer Sebastian Pirch LBI-RUD Iro Pierides WWTF LS16-034 Melanie Pieraks BSF Technologist Thomas Penz Katja Parapatics Medical University of Vienna Maria Ozsvar-Kozma JDRF 2-SRA-2017-416-S-B Matthew Oldach

Ce — M­—M­— Research Report 2017 Facts 136 137 Robert Kralovics to PersonalAssistant Mitra Eva LBI-RUD Administrative Assistant Daniel Auer* Administration Animal Care Sarah Niggemeyer Animal Care Sabine Jungwirth* Scientific Support Purchaser, Deputy Headof Patrick Stangl Wash and MediaKitchen Mate Sebök Cleaning Staff Sona Rettenbacherova Wash and MediaKitchen Daniela Reil Facility Manager Peisser Anton Johann Head of Scientific Support Gabriel ORiordain Internal Logistics Paul Kletzl Wash and MediaKitchen Amisi Fundi Nyembo Cleaning Staff Jana Brandlova Wash and MediaKitchen Sylvia Bolz~ Cleaning Staff Susanne Barcanec Scientific Support

Medical University of Vienna Sylvia Knapp to PersonalAssistant Nina Rezac Head of IT Services Michael Pilz EU LIBRA Head of HumanResources Binia MariaMeixner EU LIBRA HR ProjectManager Catherine May Lloyd Assistant Christina Licayan* Accountant Victoria Kulcsar-Mecsery Senior Accountant Karin Kukla LBI-RUD Administrative Assistant Anja Krimsky* SystemsAdministratorSenior Lasse Matias Kalevi Intellectual Property Manager Technology Transferand Saara IrinaInkinen* Senior Accountant Patrick Haiger Assistant Oliwia Hadjiaghai LBI-RUD to Kaan Boztug Personal &Scientific Assistant Isabel Grießhammer Assistant Sabine Forster Media Relations Manager Wolfgang Georg Däuble Senior IT Systems Engineer PatriciaCarey Ann Funding Manager Thomas Brandl Assistant° Sonja Bettelheim

Janek Leszczynski Magdalena Legierska Katarina Jovancevic* Marika Cappella TerezBorbala Ando Cafeteria Division Grants & Controlling Head of Finance, Kathrin Wiesendorfer PersonalAssistant KatharinaWiderhofer* HR Assistant Te Fung Fiona Tseng IT Administrator Joachim Tröster* Special Projects & Division Accounting Head of Finance, Sigrid Strodl EU LIBRA Program Manager Ph.D.Postdoc and SteinerMichaela Corinna PersonalAssistant Alexandra Stadler Head of Public Relations Eva Schweng Funding Manager Roman Schindlauer*

~ onleave * left CeMM in2017 ° onparental leave # graduated in2017

“Chemical Hematology: “Pharmacoscopy” Starting Grant Starting Grant for ChemicalEpigenetics and for functional­ tal and bioinformatic toolbox tological malignancies through schaft Fellowship Antiinfectives Proof of Concept Grant, European Molecular Biology European Molecular Biology European Molecular Biology Deutsche Forschungsgemein Boehringer Ingelheim Inter Ph.D. Fellowship Boehringer Ingelheim Fonds Ph.D. Fellowship Boehringer Ingelheim Fonds Christian ­ Legend ofGrants ­EpigenomeProgramming” ERC EPIGENOMEPROGRAMMING ERC CMIL ERC CHEMOS EMBO Long-Term Fellowship EMBO Long-Term Fellowship EMBO Long-Term Fellowship DFG Fellowship BI SLC BIF Ph.D. Fellowship Robinson-Garcia BIF Ph.D. Fellowship Lydia Metabolism and Inflammation” Florian Halbritter Martin Jäger ALTF 245-2017 ALTF 733-2016 ALTF 31-2016 AWSCHEMOS,PreSeed Organization Fellowship Organization Fellowship Organization Fellowship CDG Laboratory, national GmbH, Collaboration on solutecarriers (SLC) pgntcly aig and making ­epigenetically breaking a cancer cell– ­breaking resistance of hema personalized drugtrials” and its application to

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“A novelkinome-screen “Cancerand evolution “Evaluating viralRNA/DNA- “Co-Infectioncauseof asa “Epigeneticrisk assessment “Dissecting cell-type-specific “Myeloproliferative Neoplasms” “Myeloproliferative Neoplasms” “Crosstalk of Metabolism “Solute carrier proteins Special Research Program Special Research Program Special Research Program Studentinnen 2017 Starting Grant ­targets inMPN” for breastcancer (EpiMark)” to cells –GameofGates” Action Advanced Grant Erwin-Schrödinger-Programm International Project FEMtech Praktika PostDoc Fellowship, PostDoc Fellowship EU Project CoordinationSupport and (ERASE)” EU MSCA SLIM EU MSCA DRUGSUP ­Balance inResearch Activities” EU LIBRA Epigenomics Research Group” EU BERG ERC IMMUNOCORE ERC GAMEOFGATES FWF J3578,FWF FWF I2798, FWF I2192, FWF I1626, FWF I1575 FWF F6102 FWF F4711 FWF F4702 FFG FEMtech864423 Measures toReach Gender initiating cells(CEVIR)” ­identification of relapse- chromatin dynamicsdrivenby ­carrier proteins as thegates ovarian cancer (CINOCA)” oncogenic JAK-STATsignaling” of innate immunity” bound proteins Across SpeciEs ­method toidentify drug access chemical ­managing and biomarker development and Inflammation” drugs” ­approved and the ­ “Leading Innovative uptake of cytotoxic

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Ce — M­—M­— Research Report 2017 Facts 142 143 [Epub ahead of print]. doi: 10.1681/ASN.2017040436. pii: ASN.2017040436. 18. Oct 2017 J Am SocNephrol. Induced Arteriolopathy. ­ Dialysis- in Peritoneal Activation Complement CP. Schmitt K, ­Kratochwill F, Schaefer C, Aufricht Májek Oh J, P, Bennett KL, K, Parapatics A, ­Zaloszyc Sinn P, Warady BA, S, ­Macher-Goeppinger F, Tarantino S,Lasitschka JL, Bermejo B, ­Schaefer 4. doi: 10.7554/eLife.25125. pii: e25125. 14;6. Aug 2017 Elife. of allelic expression. regulation tissue-specific Allelomemouse reveals QJ. ­Hudson ­Barlow DP, FM, Pauler C, Bock JM, Penninger HC, Theussl Kulinski TM, ­Muckenhuber Mayer D, M, V,Sigl Bammer PC, CP,­Dotter Wenzel D, 3. btx099. doi: 10.1093/bioinformatics/ 33(13):2063-2064. Jul 1; 2017 Bioinformatics. epigenomic inR. analysis ­DeepBlueR: large-scale T. Lengauer C, Bock 2. 2017.10.002. doi: 10.1016/j.chom. 22(5):688-696.e5. Nov 8; Host Microbe.Cell 2017 Cell Entry. for Lujo Virus Host CD63 Are Factors Whelan SP. NRP2and TR, Brummelkamp Dye JM, ­Blomen T, VA, Kirchhausen YY, Chou SH, Stubbs Kuehne AI, AS, ­Herbert 1. 2017 Publications Bartosova M, M, Bartosova D, Andergassen M, F, List Albrecht Jae LT, M, Raaben Mapping the Mapping

doi: 10.1002/hep.28970. 65(4):1181-1195. Hepatology. mice. cholesterolemic inflammation in hyper of hepatic mediators sterile hyde are epitopes Malondialde Binder CJ. R, Shiri-Sverdlov C, Reinhardt C, Bock Knapp S,Bennett KL, V, S, Millischer Subramaniam G, Haas N, Papac-Milicevic Göderle L, A, F, Hladik Puhm ­Rendeiro AF, Weißer J, Walenbergh SM, Weismann Jäckel D, S, 8. May 31. Epub 2017 doi: 10.1038/nature22376. Jun 8;546(7657):307-311. 2017 Nature. signalling. GPCR anoff-switchreveal for states protein single-cell of maps Genetic wiring Jae LT, ­ AFM, Altelaar ­Bleijerveld OB, M, Raaben Stickel E, ­Blomen VA, Nieuwenhuis J, 7. [Epub ahead of print] 785683. doi: 10.1182/blood-2017-05- pii: blood-2017-05-785683. 27. Sep 2017 Blood. leukemia. prolymphocytic tor venetoclax inT-cell inhibi of BCL-2 response inhuman First PB. Staber Kubicek U, Jäger S, ­Kenner L, Merkel O, R, Moriggl Valent P, Simonitsch-Klupp I, WR, Sperr B, ­Hilgarth MB, Aretin M, Panny A, Hauswirth ­Hopfinger G, ­Mayerhoefer G, Gültekin S,Hoermann L, Kazianka N, Prutsch der Kouwevan E, 6. doi: 10.1038/ni.3727. 18(5):481-482. Apr 18; Immunol. 2017 Nat network. asocial as immune system The 5.

Busch CJ, Hendrikx T, Hendrikx CJ, Busch M, Brockmann Boidol C, Kornauth B, Menche J. A, Bergthaler Brummelkamp TR. TR. Brummelkamp Apr; 2017 ME, ME,

-

- - doi: 10.1038/nature21688. 543(7644):270-274. Nature. inacute leukaemia. domain control the by ENLYEATS JE. ­Bradner GE, Winter Orkin SH, F, S,Zhang ­Dhe-Paganon ­Offei-Addo R, Zeid O,NabetShalem B, Sanjana NE, DL, Buckley ­ JM, Roberts A, Souza HS, Seo J, Paulk H, Xie BE, Li 12. 21. Nov eCollection 2017 21929. doi: 10.18632/oncotarget. 8(59):100066-100078. Oncotarget. ­exoprotease. and anti-migratory an anti-proliferative aminopeptidase-1, Xaa-Pro upregulationhighlights of patients Hippel-Lindau invon cell carcinoma renal clear cellof ­profiling ­Schilling CA, ­Werner Jilg M, Sabido E, Schell C, Weisser ­ J, CY, Chen ­Heckelmann B, 11. Jan18. Epub 2017 doi: 10.1038/nmeth.4177. Mar;14(3):297-301. 2017 readout. tome transcrip with single-cell screening Pooled CRISPR C. Bock Alpar D, Kuchler A, LC, Schuster J, Klughammer T, Traxler P,Krausgruber ­Rendeiro C, AF, Schmidl 10. Jan21. Epub 2017 2095-6. doi: 10.1007/s11064-016- Feb;42(2):493-500. 2017 ­Treatment. Induced MPTP by Changes ­Biochemical the Cerebral Affects Toll Receptor 4 Like T, L. Corte S,Beccari ­Scorzoni G, Mariucci Sardella R, 9. Erb MA, Scott TG, TG, Scott Erb MA, Drendel V, P,Datlinger L, Roscini Conte C, 9; Mar 2017 O. O. Espadas G, G, Espadas Transcription 19; Oct 2017 Res. Neurochem NK, NK, Dastjerdi S, Dastjerdi Proteome

Methods. Nat -

­Rudashevskaya M, Rebsamen D, ­Eberharter Vogel Smet CH, GF, De 11586.1. ­ 11586.1. doi: 10.12688/f1000research. J-999. Comm pii: ISCB 6. Jun 26; 2017 F1000Res. Bock. Christoph Prize: ­Overton ISCB 2017 B. Berger 16. [Epub ahead of print] doi: 10.1083/jcb.201703061. pii: jcb.201703061. 9. Oct Biol. 2017 J Cell ­positioning. dent late endosomal and BORC-depenArl8b- a negative of regulator is ­LAMTOR/Ragulator T, Huber LA. Stasyk ­ G, Superti-Furga Bennett KL, ­Scheffzek K, T, ­Dunzendorfer-Matt S, Lechner BG, Fürnrohr Yordanov T, Tschaikner P, 15. of Review. print] [Epub ahead 2017.04.006. doi: 10.1016/j.aller. 0546(17)30077-0. pii: S0301- Jul 1. 2017 Immunopathol (Madr). review. Allergol special of anovel mutation and Report deficiency: II class MHC N. Rezaei K, Boztug A, S,Krolo Zoghi Z, Aryan 14. sji.12523. doi: 10.1111/ 85(3):227-234. Mar; J Immunol.Scand 2017 Targeted Sequencing. Turkey by Patients from bined Immunodeficiency Com inSevere Defects Investigation of Genetic K. Tezcan D, Ayvaz Boztug I, Ö,­ Sanal H, ­Boztug T, E, Hirschmugl Salzer 13.

Fogg CN, Kovats DE, DE, Kovats CN, Fogg PA, Filipek de M, S,Shabani Farrokhi I, Bilic B, Erman eCollection 2017. EL, EL, HH, HH, Lindner Araujo ­Kremser Ça˘gdaş - MEG, - L, L,

17. Epub 2017 Jul 31. Epub 2017 doi: 10.1038/leu.2017.245. 31(11):2388-2397. 2017 Leukemia. site. target aprimary as endothelial cells vascular identificationlopathy: of - vascu ­Nilotinib-induced Valent R, P.­Kirchmair G, ­Superti-Furga Wojta Wolf J, D, GH, Schernthaner B, Jilma I, Sadovnik U, Rix WR, Sperr Theurl M, C, Kaun W,Schgoer Herndlhofer S, G, Grebien F, Eisenwort G, Hoermann Huber K, Albrecht-Schgoer K, 19. [Epub ahead of print] 2017.09.008. doi: 10.1016/j.jaut. pii: S0896-8411(17)30595-4. 27. Sep 2017 Autoimmun. J encephalomyelitis. autoimmune ­experimental HDAC1 against protects deletionspecific of Ellmeier W.­ ATcell- G, Steiner ­Waisman A, C, Bock M, ­Schuster P, T,­Matthias Penz C, Seiser K, Hirahara IA, V,­Saferding Mufazalov Gülich AF, Müller L, Boucheron N, L, Andersen P,Hamminger Bonelli M, 18. doi: 10.1038/leu.2017.351. 18. Dec 2017 ­Leukemia. onimpact survival. and ­Biological features acute myeloid leukemia: in ­Chromothripsis G. Martinelli R, Kralovics ­ M, Cavo S,­ Paolini Z, Racil M, Steurer Doubek M, Guadagnuolo V, L, Semerad T, S,Haferlach ­Soverini ­Testoni I, Iacobucci N, C, Baldazzi A, Ferrari E, Ottaviani E, Franchini Solli V, A, Padella Rorá AGL, di C, Papayannidis E, Fonzi JDM, Feenstra

Hadzijusufovic E, E, Hadzijusufovic Preglej T, L, Göschl MarconiG, MC, Fontana Simonetti G, Nov; M, M, Manfrini

13058-z. doi: 10.1038/s41598-017- Sci hepatic inflammation. murine oxLDL-dependent lipids trigger ­lysosomal prone to accumulate macrophages derived R. ­Shiri-Sverdlov Binder Hofker CJ, MH, Verheyen D, F, Lütjohann ­ MH, ­Lenders ­Gastroenterology. ­Inflammation. During Is Altered and Individuals Function inHealthyAbundant Are Microbiota Intestinal to Reactivity T Cells With CD4+ Tissue-Resident and Circulating F. Powrie Teichmann S, Keshav SA, A, Bergthaler ­Investigators, Cohort Oxford IBD A; McMichael HH, Uhlig BMJ, Owens SH, ­Duncan 21. 4. Aug Epub 2017 2017.07.047. doi: 10.1053/j.gastro. 153(5):1320-1337.e16. ­Walenbergh AV,Bitorina T, Hendrikx ­Oligschlaeger 22. mcp.RA117.000186. doi: 10.1074/ RA117.000186. pii: mcp. 4. Dec 2017 Mol Proteomics. Cell signatures. molecular mechanism-associated patho­proteome reveal effluent neal dialysis ontreatment the perito of alanyl-glutamine Effects K. Kratochwill C, Aufricht A, Vychytil SL, Alper Bennett KL, A, ­Lichtenauer Majek P, Mueller AC, K, Parapatics ­Wagner A, M, Unterwurzacher Danne C, Campion S, C, Danne S, This A, Datsi Suijker KIM, MJT, WendtStubbington E, 20. Rep. Houben T, Boehm M, R, Herzog Hegazy AN, West AN, NR, Hegazy 2017 Oct 2;7(1):12550. 2;7(1):12550. Oct 2017 SMA, SMA, Gijbels MJJ, Y,

2017 Nov; 2017 Blood-­ - -

eCollection 2016. doi: 10.1038/npjsba.2016.27. 27;2:16027. Oct 2016 BiolNPJ Syst Appl. infection. to VSV response of the macrophage map resolved molecular G. ­Superti-Furga Bennett KL, Colinge J, R, Kralovics C, Cleary T, Penz Brückner M, S, Scorzoni A, Stefanovic Sabler M, ­Moskovskich A, JW,Bigenzahn M, Rebsamen Müller AC, Snijder B, GI, ­Vladimer 26. Jun 1. Epub 2017 blood-2016-11-754416. doi: 10.1182/ 130(4):542-553. Jul 27; 2017 Blood. receptor-2. Toll-like via ­formation thrombus ­arterial synthesis andfactor hepatic von Willebrand regulate ­microbiota ­Reinhardt Walter W, Ruf U, S, Massberg ZM, Ruggeri Binder Jurk CJ, K, Lämmle B, S, JF, Haberichter Baines BrühlMV, P, K, Ebner Rausch E, S,Wilms ­Subramaniam C, Reiss N, Hörmann Kollar B, A, ­Khandagale T, Hendrikx M, Lillich 25. j.devcel.2017.05.018. doi: 10.1016/ 41(5):456-458. Jun 5; 2017 Cell. Dev Sidekick. Wnt’s Just R-spondin IsMore Than 24. 03796-5. doi: 10.1038/s41598-017- Jun 14;7(1):3494. 2017 Rep. Sci steatohepatitis. murine lipid metabolism in Dregulates Cathepsin ­ Hofker MH, D, Lütjohann FG, Schaap J, S,Plat Friedrichs Gijbels PJ, MJJ, Gorp van ­Walenbergh T, AV,Hendrikx Bitorina ­Oligschlaeger 23. Kandasamy RK, RK, Kandasamy Jäckel K, S,Kiouptsi OJ. Huels Sansom DJ, Houben T, C. C.

R. R. Shiri-Sverdlov SMA, SMA, Gut Y,

­ A time- s41598-017-10637-y. doi: 10.1038/ 7(1):11289. Rep. Sci LCMV-induced hepatitis. inamodel of disease TREM2aggravates sensor lipid- The A. Bergthaler Knapp S, I, Mesteri Schliehe C, A, ­Bhattacharya K, Lakovits A, ­Hladik B, Vilagos A, Lercher 30. Review. doi: 10.1039/c6ib00215c. 20;9(2):97-108. Feb 2017 Integr Biol (Camb). approaches. signaling ­interdisciplinary medicine: ­network ­ Next ­Superti-Furga ­Schneider 29. eCollection 2017. pone.0169892. doi: 10.1371/journal. Jan12;12(1):e0169892. 2017 One. PLoS Disease. ­Invasive during ­meningitidis inNeisseria Changes Genetic ­Host Within- Reveals Sequencing ­Comparative Genome Müller T, C. Schoen A, Goesmann M, Frosch V,Mitesser Vogel U, Blom M, J, Dittrich 28. journal.ppat.1006758. doi: 10.1371/ 13(12):e1006758. 20; Dec Pathog.PLoS 2017 Lprotein. virus ingitis choriomen ­lymphocytic withthe ­interacting tion of host proteins Characteriza A. Bergthaler Menche J, ­Bennett KL, DD, Pinschewer James LC, R, Sacco A, Stukalov Májek P, A, ­Bhattacharya L, Kosack M, Sahin B, ­Vilagos Schliehe C, M, Caldera 27.

Kosack L, Gawish R, Gawish R, L, Kosack T,Korcsmaros J, Klughammer ­ K, Khamina generation of 12; Sep 2017 MV, G. G. Lercher A, A, Lercher

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Ce — M­—M­— Research Report 2017 Facts 144 145 s00415-017-8710-x. doi: 10.1007/ 19. Dec 2017 JNeurol. spectrum. the expanding ­dysfunction: with immunological body myopathy polyglucosan cause may of RBCK1 part N-terminal ­Mutations outside the F. Zimprich A, Hahn K, Boztug A, ­Zimprich KG, Schmetterer MW, RLJ, Schmidt Kilimann A, Schänzer Strom TM, TB, Wagner Haack M, J, Simonitsch-Klupp Rath I, 34. Jun 20. Epub 2017 jth.13737. doi: 10.1111/ 15(8):1625-1639. Aug; 2017 J Thromb Haemost. injury. acute lung in acid-aspiration-induced effects anti-­inflammatory protective exerts factor but not tissue epithelial G. ­Schabbauer Knapp S, N, Mackman A, Assinger JA, Schmid B, Jilma B, Niederreiter Ay C, V, Hell L, ­Horvath H, Datler WC, Schrottmaier 33. 1. Sep Epub 2017 doi: 10.1074/jbc.M117.801464. 292(43):17643-17657. 27; Oct 2017 J Biol Chem. histone binding. modulates multivalent multidomain protein linkerinterdomain ina A histone-mimicking Slade D. Kubicek R, S,Konrat T, E, Schirghuber Kaufmann 32. 27. Sep Epub 2017 s10875-017-0446-y. doi: 10.1007/ 37(8):790-800. Nov; J ClinImmunol. 2017 Experience. ­Single-Center a of LRBA Deficiency: Multiple Presentations A. F, Ikinciogullari Dogu K, Boztug A, Ensari A, Kansu Z, Siklar Yavuz B, Dalgic G, Kendirli T, Kuloglu Z, Aytekin C, Islamoglu C, NK, ­Haskologlu S, Serwas 31. genotype-phenotype ­genotype-phenotype Krenn M, Salzer E, E, Salzer M, Krenn JB, Kral-Pointner Kostrhon G, S,Kontaxis Kostel S, Bal Myeloid Myeloid

Epub 2017 Sep 7. Sep Epub 2017 BAHA.117.310002. doi: 10.1161/ATV Nov;37(11):2064-2074. 2017 Thromb Vasc Biol. Arterioscler Cholesterol Biosynthesis. HMGCR and Degradation of aKeyDeterminant as IdentifiesScreen UBXD8 Genetic ­Mammalian Haploid Zelcer N. Roitelman ­ J, Stickel E, H, ­Gelberg-Etel M, den Berg van Moeton M, Tan M, S, Scheij J, Raaben 38. May 22. Epub 2017 nchembio.2382. doi: 10.1038/ 13(7):771-778. Jul; Biol. 2017 Chem Nat theing androgen receptor. target uncovers asynergy of thescreen CLOUD S. ­Kubicek Menche Bennett KL, J, K, Kratochwill C, Bock P,Stattin Ivanov V, Colinge J, Folkvaljon Y, G, ­Dürnberger Boidol M, ­Schuster B, T, Penz R, ­Herzog Wagner M, A, Caldera Müller AC, E, ­Schirghuber Sdelci S, CH, Lardeau Markt P, A, F, Klepsch ­Ringler 37. [Epub ahead of print] 3409-y. doi: 10.1007/s00705-017- May 18. Arch 2017 Virol. ing. self-process ­autocatalytic absence of G1 protein: T.Skern Vaccinia virus 36. [Epub ahead of print] doi: 10.1038/leu.2017.230. status. and JAK2 mutational type disease administration, hydroxyurea tion withage, associa tive neoplasms: of myeloprolifera phase TP53 mutations inchronic Low-burden Doubek M. S, Pospisilova R, Kralovics Mayer J, M, Penka H, Gisslinger B, Gisslinger V, J, Bystry Kissova M, Slavikova Fiedorova K, B, Kantorova K, Plevova Tom L, Tichy B, N, Radova J, Kabathova J, Malcikova 35.

Loregger A, A, Loregger MP,Licciardello A, Bergthaler FGG, Leite S, Pavlova B, Kubesova 2017 Jul 24. Jul 24. 2017 Leukemia. A combinatorial A combinatorial T,Brummelkamp - - - - - 12. May 12. Epub 2017 cdd.2017.71. doi: 10.1038/ 24(6):953-954. Jun; Differ. Death Cell 2017 STAT5game: inanew role. V.Sexl Itisadifferentiation 42. May 12. Epub 2017 2017.02.022. doi: 10.1016/j.ijantimicag. Jul;50(1):55-62. 2017 Int JAntimicrob Agents. efflux. macrophage ­inducedinflammation- amide reversing by and pyrazin ­isoniazid of activity bacterial theenhances antimyco Chloroquine Nemeth J. Sander P, M, Zeitlinger AS, Zinkernagel A, ­Andreoni F, Stenzinger K, O,Schilcher Sharif Strommer Molin S, Dal M, 41. [Epub ahead of Review. print] doi: 10.1016/j.coi.2017.10.005. 26;50:14-20. Oct 2017 Immunol. Opin Curr insultto injury.adding in innate immunity: Heme and hemolysis 40. Jun 21. Epub 2017 doi: 10.15252/embj.201695347. Jul 14;36(14):2107-2125. 2017 J. EMBO turnover. protein modulating by pancreatic β-cell survival axiscontrols regulatory A TRPV1-to-secretagogin T. Harkany Groop L, ­Hökfelt T, Wagner L, ­Kubicek G, S,Lubec R, Sandberg G, Szabó V, F, DiMarzo Piscitelli Borók E, ­Romanov RA, Mulder J, Schnell R, Å,TortorielloSegerstolpe G, P, Storm Szodorai E, 39.

Maurer B, Farlik M, M, Farlik B, Maurer Selchow U, Matt P, Knapp S. R, Martins F, Girach Malenczyk K, - -

cvr/cvx129. doi: 10.1093/ 113(10):e29-e30. 1; Aug 2017 Res. Cardiovasc and beyond. research disease for cardiovascular anew paradigm medicine: 46. 0009-0. eCollection 2017. doi: 10.1038/s41540-017- 13;3:10. Mar 2017 BiolNPJ Syst Appl. gene pools. associated ­ disease- into predictive profiles gene expression personalized ­Integrating AL. Barabási R, Dobrin F, Baribaud MJ, Loza PJ, Branigan A, Sharma 45. doi: 10.1161/JAHA.117.005747. 6(9). pii: e005747. 7; Sep 2017 Assoc. J Am Heart Atherosclerotic Disease. AdvancedPatients With Better Outcome in With Associated Are BCells Switched Memory of (Un) Levels High SCA. de Jager IE, Hoefer Binder CJ, G, ­Pasterkamp den HM, Ruijter de GJ, Borst GN, ­Fredrikson H, S,Björkbacka Haitjema de Weg van SM, MO, Kozma A, Gohar Duijvenvoordevan A, 44. 2017.10.021. doi: 10.1016/j.molcel. Nov 16;68(4):797-807.e7. 2017 Mol Cell. MUTYH. by IsMasked Repair of Nucleotide Excision Independent ­Damage of UV-Induced DNA Repair Kubicek JI. S,Loizou M, Orozco J, Weil Neesen B, A, Ringler CH, Lardeau M, Owusu M, Wiedner J, Silva da Ferreira SC, Moser 43. Network Network Menche J. Menche Guney E, J, JAL, Meeuwsen F, Battistini A, Mazouzi CM, CM, ­Gijsberts 10.1038/s41467-017-01439-x. doi: Nov 1;8(1):1238. 2017 Commun. Nat ­anemia. complex and Fanconi the BLM helicase between viable interactions synthetic identify screens genome-wide Parallel JI. Menche Loizou J, Ideker T, C, Bock Jackson SP, 47. Kralovics R, Schuster M, M, Schuster R, Kralovics R, F, Slavkovsky ­Schischlik L, ­Robinson-Garcia J, Silva da ­Ferreira M, Wiedner A, Mazouzi Velimezi M, Owusu G, 50. target.20488. doi: 10.18632/onco 103031. 24;8(61):103014- Aug 2017 cancer. Oncotarget. ­thyroid in ­inhibitor, dasatinib, to the Src ­resistance mediate pathways andmTOR MAPkinase ofactivation the AKT/ Sustained RE. Schweppe U, Rix G, ­Superti-Furga DM, Klimczak BM, Kuenzi ­Beadnell TC, 49. 7. Sep Epub 2017 10.1016/j.cmet.2017.08.014. doi: 26(5):788-800.e6. Nov 7; 2017 Metab. Cell Microenvironments. Complex Tissue Single Cells within of ­Configurations Metabolic Exploring A. ­Wagner O,Haschemi P, M, Bergmann Starkl Groeger M, ­Ponweiser E, J, Laengle Knapp B, 48. 16. Aug Epub 2017 nature23669. doi: 10.1038/ 106-110. Nature. regulators. protein PD-L1 and CMTM4as ­Identification of CMTM6 TNM. ­Schumacher TR, Brummelkamp J, Borst Y,Xiao AJR, Heck Wessels Blank CU, LFA, Horlings HM, Broeks A, I, Hofland EA, Rozeman M, MEW, Slagter ­Logtenberg Wu W, E, de Vries Jae LT, R, Gomez-Eerland

Moder M, Moder M, KM, Mishall C, Nagy A, Miller Sun C, R, Mezzadra 7;549(7670): Sep 2017

-

nm.4315. Epub 2017 Apr 17. Epub 2017 nm.4315. doi: 10.1038/ 601-610. May;23(5): 2017 Med. Nat high-cholesterol diet. helper Tcells to a of follicular response B cells control the zone Marginal Z. Mallat Binder de Pompa la CJ, JL, Yeo M, ­Kneilling GSH, R, Schirmbeck N, Figg L, Kitt A, Finigan D, Marcus J, ­Tsiantoulas Raffort D, ­Newland S,Weller S, BYH, Lam L, Masters 54. Nov 16. Epub 2017 doi: 10.1126/science.aao5676. 358(6369):1453-1456. 15; Dec 2017 Science. activity. detyrosinating ­Vasohibins encode tubulin ­Brummelkamp VA, Blomen A, Knipscheer P, Perrakis Celie P,Stickel M, E, Altelaar A, Mazouzi ­Bleijerveld OB, A, ­Adamopoulos 53. doi: 10.1038/ncomms15781. Jun 7;8:15781. 2017 Commun. Nat mice. ment of in atherosclerosis cells control the develop Type-2 innatelymphoid Z. Mallat AJ, Habenicht ANJ, McKenzie Binder CJ, HR, ­Rodewald AJ, Finigan LL, Kitt Hu D, AP, C, Sage Yin Taleb M, Nus S, Walker JA, S, Clément M, Mohanta 52. of print] [Epub ahead nar/gkx425. doi: 10.1093/ May 17. 2017 Res. Nucleic Acids data. sequencing from linked genetic variants ­ of disease- prioritization interactive VCF.Filter: C. Bock K, Boztug J, T,Hirschmugl Dmytrus ­Jimenez-­ 51. Nus M, Sage AP, Sage Y, Lu M, Nus Nieuwenhuis J, Newland SA, Müller H, Heredia R, Krolo A, A, Krolo R, Heredia TR. TR. - Epub 2017 Sep 13. Sep Epub 2017 2017-04-777383. doi: 10.1182/blood- 1953. 26;130(17):1949- Oct 2017 assembly. Blood. synapse and migration during architecture lymphocyte human affects severely deficiency WIP Dupré L. W, K, Schwinger Boztug Urban C, Antón IM, T, E, Hirschmugl Salzer J, Rey-Barroso R, Houmadi 58. of print] [Epub ahead onc.2017.341. doi: 10.1038/ 18. Sep 2017 ­properties. invasive with highly tion of cells melanoma subpopula A slow-cycling Herlyn M. R, Somasundaram Wagner SN, Bennett KL, JK, Jensen A, Raj S,XuX, Liu ShinS,Keeney F, D, Hristova L, Li K, Parapatics Müller AC, S, Wang Shaffer JX, 57. Jun 28. Epub 2017 doi: 10.1056/NEJMoa1615887. Jul 6;377(1):52-61. 2017 JMed. NEngl Thrombosis. Enteropathy,Losing and ­ Protein- ­Early-Onset CD55 Deficiency, MJ. Lenardo K, ­Boztug T, S,Erkan SuHC, Sari R, Kain D, Ertem HL, Leavis Houwen RHJ, ­Snapper SB, I, Ogulur M, Gulsan Z, Baris A, Kiykim A, Krolo McElwee JJ, ­Unlusoy AksuA, S,Folio LR, Pittaluga Y,Zhang HF, Matthews NK, F, Serwas S,Ozcay Baris Tutar ­Karakoc-Aydiner E, E, AR, Morawski ÖF, Beser B, ­Dalgic Conde­Domínguez C, WA, Comrie Ardy RC, 56. Review. joim.12614. doi: 10.1111/ 281(6):534-553. Jun; 2017 Med. J Intern low levels. extremely oftoo low? Possible risks LDLCan cholesterol be L. Yvan-Charvet MJ, Tikkanen J, Starup-Linde ­Rosenson RS, P, ­Parhofer Parini KG, ­ E, ­Farinaro A, Cohen von J, Eckardstein ­Cedazo-Minguez Binder Björkhem CJ, I, G, Assmann Angelin B, 55.

Pfajfer L, Seidel MG, Seidel MG, L, Pfajfer M, Maurer M, Perego A, Ozen Olsson AG, Müller-Wieland D, Oncogene. A, A,

- 7180-0_11. doi: 10.1007/978-1-4939- 2017;1643:147-154. MolMethods Biol. Microvesicles. ­Circulating Epitopes on Specific ­ Oxidation- Recognizing IgMAntibodies ­Natural of Characterization 62. 04438-6. doi: 10.1038/s41598-017- Rep. Sci Bcells. ­regulatory atheroprotective with BAFF to promote synergizes Angiotensin II ­ Z, Mallat Y, Zhang A, Giraud Tedgui A, X, Loyer Zeboudj L, Binder ­ CJ, ­ B, Esposito Herbin O, J, Joffre 61. oncotarget.15146. doi:22615. 10.18632/ Apr 4;8(14):22606- 2017 Oncotarget. inhibitors. to BCR-ABL1sensitivity cellsleukemia affects chronic myeloid primary of ­Differentiation status S,Porkka K. Mustjoki Tyner JM, Enserink JW, BJ, Druker H, ­Hjorth-Hansen ­Wennerberg O, Kallioniemi CA, Heckman T,Pemovska Kontro M, Mpindi JP,Andersson EI, H, S,Kuusanmäki Potdar Ayuda-Durán P, CA, Eide 60. 4. Dec Epub 2017 doi: 10.1172/JCI94509. Jan2;128(1):387-401. 2018 JClinInvest. ­neoplasia. mutation fordriver Tcell STAT5BN642H isa V,Sexl R. Moriggl Valent P, Rülicke T, Müller M, C, Bock Kubicek M, S,Farlik Kenner L, M, Hengstschläger Grebien F, Z, Kazemi J, F, Pencik ­Halbritter Kolbe T, M, Elabd A, Boersma H, Nivarthi T, Javaheri E, ­Grundschober R, ­Grausenburger M, Prchal-Murphy 59.

Puhm F, Binder CJ. F, Binder CJ. Puhm PO, Pietarinen B, Maurer HTT, Pham Ponnuswamy P, 2017 Jun 23;7(1):4111. Jun 23;7(1):4111. 2017 Ait-Oufella H. H. Ait-Oufella Tedder TF, Laurans L, L, Laurans K, K,

Ce — M­—M­— Research Report 2017 Facts 146 147 Epub 2017 Jun 15. Jun 15. Epub 2017 SAHA.117.310884. doi: 10.1161/CIRCRE Jul 21;121(3):270-281. 2017 Circ Res. Atherosclerosis. the Development of Limit Cell Responses Plasma ­Dependent X-Box Protein-1 Binding Z. Binder Mallat CJ, L, Masters AJ, Finigan ­Tsiantoulas Newland D, SA, J, Chakraborty ­Bagchi 66. 0000001035. doi: 10.1097/MPH.000000 Oncol. JPediatr Hematol Pitfall. AnOncologicalSpine: Infiltration of theWith Actinomycosis Thoracic A. Attarbaschi G, Mann L, Kager K, Boztug G, Amann W, Krizmanich K, Lakatos W, ­Friesenbichler Hutter C, 65. Jan;16(1):88-101. 2017 Ther.Mol Cancer Sensitivities. Sarcoma-specific Ewing Identifies Screening Drug Combinatorial G. ­Superti-Furga H, S, Kovar Brunak Olsen JV,­Bennett KL, Toretsky Mutz C, JA, Papamarkou T, Huber KV, ­Tsafou KP, KB, Emdal 64. 03129-6. doi: 10.1038/s41598-017- Jun 8;7(1):3091. 2017 Rep. Sci transporter. tion of the ABCB1 efflux inhibi via neuroblastoma of YM155 in cytotoxicity potentiates Lapatinib Kolch G. W, Superti-Furga Papamarkou T, S, Brunak Tsafou KP, GE, Winter Huber KVM, M, Halasz 63. Sage AP, Sage M, Nus Ronceray L, B, Radic-Sarikas B, Radic-Sarikas 2017 Dec 12. 12. Dec 2017 -

- 1380515. Epub 2017 Sep 25. Sep Epub 2017 1380515. doi: 10.1080/17474086.2017. Nov;10(11):961-973. 2017 Hematol. Rev Expert use. clinical and ­significance –their ­neoplasms in myeloproliferative Mutations R. Kralovics 70. s13059-017-1344-6. doi: 10.1186/ 18(1):208. 30; Oct Biol. 2017 Genome splicing of alternative determinant isthe main mis-splicing ­ The L. Duret Meyer E, A, Necsulea ­Blugeon C, Rocher V, JL, Parmley 69. doi: 10.1016/j.jaci.2017.11.023. 6749(17)31899-7. pii: S0091- 14. Dec 2017 ClinImmunol. J Allergy lymphocytes. Thelper syndrome Aldrich inWiskott-­ instability R-loops genomic cause YM. Vyas MM, Seidman DupréL, Wen HD, Ochs KK, 68. 2017.01.071. doi: 10.1016/j.celrep. 21;18(8):1893-1905. Feb 2017 Rep. Cell Environment. the ImmuneShape Lung Induced Type 2Pathways ­ First-Breath- Knapp S. ANJ, McKenzie I, Mesteri Jolin H, JM, ­Warszawska O, Sharif Korosec A, A, Hladik K, ­Lakovits P, S,Starkl ­Scanlon R, Martins BMJ, Rana 67.

Schischlik F, Schischlik Saudemont Popa A, B, SS, Han K, Sarkar S,Gorki AD, Saluzzo fitness cost fitness cost of ­patterns.

doi: 10.1055/s-0043-120571. Nov 28. 2017 Diabetes. ­Endocrinol ExpClin Diabetes. ­Heterogenous Group of AVeryMody Genes: ByCaused Mutations in Monogenic Diabetes Not ­ A, Kansu ­İkincio˘gulları Kulo˘glu A, Z, ­Boztu˘g Do˘gu K, F, S, S,Ceylaner Ellard SE, Johnson Flanagan MB, 73. Jan30. Epub 2017 doi: 10.1038/nm.4273. Mar;23(3):386-395. 2017 Med. Nat sarcoma. in Ewing spectrum disease defines a heterogeneity ­methylation ­Tomazou C, Bock H, Kovar O, Ambros PF, Delattre Dirksen U, R, Windhager Holter W, R, ­Ladenstein V,­Laurence Michon J, Terrier G, P, de Pinieux A, Leithner B, Huppertz B, Liegl-Atzwanger B, Rinner D, Strunk K, Schallmoser AT, Amaral E, de Álava E, Sorz Hutter C, Ambros IM, WalderBouvier R, D, P, ChampigneulleFreneaux J, ­Guillemot Lapouble E, D, Surdez D, J, Hadler M, Schuster A, Schönegger P, Datlinger J, Klughammer 72. Jun 22. Epub 2017 j.molcel.2017.05.025. doi: 10.1016/ 67(1):30-43.e6. Jul 6; 2017 Mol coli. Cell. E. TranscriptionRegulate in Aptamers Polymerase RNA Natural Nudler E. V, Sedlyarov R, Schroeder Lybecker B, M, ­Zimmermann V, Epshtein I, ­Bilusic N, Rziha Popitsch N, Rescheneder P, A, Magán 71. ıklar Z, de Franco E, E, de Franco Z, Şıklar G, Pierron SheffieldNC, N, Sedlyarova Berbero˘glu M. EM. EM. DNA DNA 00452-4. doi: 10.1038/s41467-017- 19;8(1):607. Sep 2017 Commun. Nat resistance. and ­heterogeneity therapy induce tumor B-cells Tumor-associated ­ Herlyn M, Herlyn ­ D, L, Schuchter BJ, Czerniecki Wargo J, MA, Davies ­Watson H, Schaider I, Bennett K, M, Beqiri ­ A, Raj ­ Gavin BJ, Choi H, L, Grinman C, ­Ellingsworth GV, Long M, Damle DT, Scolyer RA, ­Frederick Tetzlaff Wu G, L, Chen M, C, Hudgens R, Lang Koller J, K, ­Rappersberger F, ­Weihsengruber V, ­Bauer-Pohl A, Jalili G, Karanikas Mayerhöfer M, C, ­Hafner M, Maurer R, Hards J, Griss K, Garg Q, Liu T, Tian J, WeiZhang Z, D, Hristova Wagner C, XuX, C, Krepler M, ­Perego ­Fukunaga-Kalabis G, Zhang 75. 3026(17)30208-9. doi: 10.1016/S2352- 4(12):e595-e606. Dec; 2017 Haematol. Lancet study. pilot open-label, asingle-arm, from results interim malignancies: haematological aggressive for patientsscreening with ex-vivo drug Image-based G. Superti-Furga PB, Staber Valent P, Kubicek U, S,Jäger H, Gisslinger R, Kralovics WR, Sperr Kenner L, GW, B, Korkmaz Prager Felberbauer F, Müllauer L, ­Simonitsch-Klupp Ocko K, I, ­Mayerhoefer G, ­Jeryczynski Sabler M, A, ­Ringler Merkel N, O, Prutsch JW, G, Bigenzahn Hoermann L, Gültekin S,Kazianka der Kouwe van E, Choi HS, O, de Fuente la Lopez C, Kornauth Schmolke AS, K, Miura N, Krall 74.

Somasundaram R, R, Somasundaram GI, Vladimer Snijder B, N, Gross L, L, Scholler Gross N, Flaherty K, K, Flaherty Wagner SN. Wagner SN. ME, ME, M, M, Dunagin M, M, nature21032. Epub 2017 Jan11. Epub 2017 nature21032. doi: 10.1038/ 412-416. Jan19;541(7637): 2017 Nature. ­Picornaviridae. ofand clearance entry between switch a represents PLA2G16 TR. ­Brummelkamp JE, Carette A, Perrakis Kuppeveld van FJ, H, Janssen Thibaut Nieuwenhuis HJ, J, J, Baggen M, ­Brockmann den ­ van ­Blomen von ­ 78. 02;8:1250. Oct 2017 Front Immunol. in: Erratum eCollection 2017. fimmu.2017.00449. doi: 10.3389/ 8:449. May 1; Front Immunol. 2017 of Deficiency. RTEL1 neity and Heteroge Molecular MW. ­Wlodarski K, Boztug Niemeyer C, EhlSR, K, Schwarz B, Strahm C, Jandrasits E, Lausch A, Rensing-Ehl M, Seidl L, Rindle E, Laack Woessmann W, G, Escherich ­Verdu-Amoros Hauch H, JJ, Thomay G, K, Göhring U, Pannicke Boulton SJ, Vannier D, Schindler JB, N, Damatova M, ­Hoemberg NK, Serwas A, Karow S, Hirabayashi M, Rizzi 77. eCollection 2017. fimmu.2017.01250. doi: 10.3389/ 8:1250. 2; Oct Front Immunol. 2017 of Deficiency. RTEL1 Heterogeneity ­Molecular and Clinical ­Corrigendum: MW. ­Wlodarski K, Boztug Niemeyer C, EhlSR, K, Schwarz B, Strahm C, Jandrasits E, Lausch A, Rensing-Ehl M, Seidl L, Rindle E, Laack Woessmann W, G, Escherich ­Verdu-Amoros Hauch H, JJ, Thomay G, K, Göhring U, Pannicke Boulton SJ, Vannier D, Schindler JB, N, Damatova M, ­Hoemberg NK, Serwas A, Karow S, Hirabayashi M, Rizzi 76.

E, E, Castelmur Staring J, J, Staring SS, Sahoo C, Speckmann SS, Sahoo C, Speckmann

VA, VA, LG, Hengel LG, Clinical Clinical

- ebiom.2017.11.024. doi: 10.1016/j. Dec;26:17-24. 2017 . EBioMedicine. Proposal AConsensus Conditions: Neoplastic Malignant ­ of Pre- ­Classification and ­Terminology Horny HP. Proposed G, Superti-Furga C, Schiffer SotlarK, PB, Staber WR, Sperr A, Reiter A, Orfao DD, Metcalfe Majeti R, H, Kreipe Kenner U, Jäger L, O, Hermine G, Hoermann T, Haferlach J, Gotlib SJ, Galli TI, George C, Bock Arock M, 82. 695940. doi: 10.1182/blood-2016-10- 9;129(6):667-679. Feb 2017 Blood. ­neoplasms. myeloproliferative ofphysiology classical pathoand molecular Genetic basis R. Kralovics 81. 2. Mar Epub 2017 2016.159947. doi: 10.3324/haematol. 102(6):995-1005. Jun; 2017 ­Haematologica. cells. in erythroid stability to cytoskeletal V.Sexl Cdk6contributes PW, Hinds M, von Lindern Kubicek S, ­Bennett KL, Muckenthaler MU, J, S,Neves Altamura DA, Fux AS, Tigan M, Prchal-Murphy Glösmann M, Kollmann K, 80. 03688-8. 10.1038/s41598-017- doi: Jun 14;7(1):3540. 2017 development. splenic Bcell abnormal in results that signaling BCRleads to increased IgMdeficiency Secreted Binder CJ. H, Jumaa Z, Mallat A, Bergthaler B, Bartolini-Gritti 79. Valent P, AkinC, Vainchenker W, Scheicher RM, IZ, Uras Tsiantoulas D, Kiss M, M, Tsiantoulas Kiss D,

Sci Rep. Sci ­

6b05065. Epub 2017 Mar 15.h Mar 6b05065. Epub 2017 doi: 10.1021/acs.analchem. Apr 4;89(7):3847-3852. 2017 Chem. Anal and Peptides. Proteins hyde-Modified Malondialde Identify To Strategy ­Analytical A Comprehensive Binder Bennett KL. CJ, K, Uchida K, Nowikovsky SR, Austin CJ, Busch 86. Apr 24. Epub 2017 doi: 10.1038/nchembio.2360. Jun;13(6):681-690. 2017 Biol. Chem Nat drugs. potential of common immunomodulatory of theGlobal survey G. Superti-Furga U, Jäger Kubicek S,Helleday T, Knöbl P, OL, de Fuente la UW,­Berglund Sabler M, A, Ringler Sanjiv K, CH, Lardeau Huber KVM, JW, Bigenzahn N, Krall 85. leu.2016.365. doi: 10.1038/ Jan6. 2017 Leukemia. leukemia. blastic childhood acute lympho P2RY8-CRLF2-positive of tional landscape Genomic and transcrip R. ­Panzer-Grümayer OA, Haas G, Mann MA, Horstmann M, Schrappe von ­ H, Cavé C, Bock M, Schuster A, ­Attarbaschi S, F, Fischer Kraler K, Nebral U, Zur Stadt A, ­Mecklenbräuker G, Cario C, ­Eckert 84. oncotarget.15481. doi: 10.18632/ 23072. Apr 4;8(14):23061- 2017 Oncotarget. of Ph+ CML. crisis blast multi-resistant in response molecular induced deep persistent ­ rotation- TKI C. Mannhalter G, Superti-Furga WR, Sperr Müllauer L, E, Hadzijusufovic G, ­Gleixner KV,Hoermann Kubicek S, A, Ringler Boidol M, B, Schneeweiß 83. Stackelberg A, A, Stackelberg Weißer J, Ctortecka C, C, Weißer Ctortecka J, Snijder B, GI, Vladimer C, Vesely Frech C, Valent P, Herndlhofer S, - -

- Epub 2017 Apr 24. Apr 24. Epub 2017 doi: 10.1038/nchembio.2378. Jun;13(6):575-576. 2017 Biol. Chem Nat splicing. DCAFinating degradation: 88. Jun 29. Epub 2017 2017.06.004. doi: 10.1016/j.molcel. Jul 6;67(1):5-18.e19. 2017 Mol Cell. Recruitment. ­Independent of CDK9 Elongation Factors Transcription Master as ProteinsFunction domain Bromo BET JE. Bradner LS, Churchman Kelliher MA, NS, Gray CY, Bauer S, Lin S, Dastjerdi Olson CM, K, Lachance J, Paulk TG, Scott R, Zeid JM, Roberts CJ, Ott A, Souza Iulio J, di JM, Reyes S, Vittori JE, ­Roderick ErbMA, DL, Buckley 87.

Winter GE. Protein GE. Winter Mayer A, GE, Winter -

Ce — M­—M­— Research Report 2017 Facts 148 149 "Ph.D. Alumni Gallery", Vienna, Dr. MichaelHäupl. the Bellen and theMayor of Prof. Alexander Van der In 2017, we installed the ­graduates ­ and it ispartof CeMM’s CeMM is very proud officially ­ culture to­ of its Ph.D. students ­President of Austria, inaugurated by celebrate collectively. “Ph.D. Alumni Gallery”. Installed in the staircase, AlumniGallery”. inthe staircase, “Ph.D. Installed Van der Bellen and the Mayor of Vienna, The official inauguration of the Ph.D. Alumni inauguration of thePh.D. The official The “10-year” anniversary of CeMM celebrated of CeMM anniversary The “10-year” where all CeMMies frequently pass by, pass frequently where of each allCeMMies Johanna Klughammer (Bock Group), (Bock Johanna Klughammer Johannes Bigenzahn (Superti-Furga Group), and Rui (Superti-Furga Bigenzahn Busch (BinderBusch Group), (Bennett Dijana Vitko Lui Jana Group), (Nijman Mair Clara Barbara students. Ph.D. 3rd, onDr. Häupl, October Michael CeMM visited Martins (Knapp Group).­Martins In 2017, eight Ph.D. students successfully successfully students Ph.D. eight In 2017, learn to representatives ­Häupl met withPh.D. present. The CeMM Ph.D. program started witha started program Ph.D. The CeMM present. portray and remember every one of and them remember every forportray Group), Ferran Fece de la Cruz (Nijman Group), (Nijman de Cruz la Fece Group), Ferran Gallery was a special occasion where none occasion other aspecial was ­Gallery ments. Their visit was a great honor agreat Theirments. visitwas and reflects newly graduating student will receive hisor receive her will student newly graduating 2017 was a fabulous occasion to commemorate to occasion afabulous was in 2017 the importance ofthe and inour importance the we pride take Van the der installation. Bellen reveal to and Prof. Alexander thethan President of Austria, their including photo, tile, ­individual name, the what we call come, to many we started years remarkable achievements and permanently to the student as asouvenir.the as student begiven –and to asecond will tile theto gallery beceremoniously to day ontile graduation added now From every on, thesis. Ph.D. the graduate’s the successes of CeMM Ph.D. students past and past students Ph.D. ofthe CeMM successes by the success end had 49students of 2017, about the Ph.D. program and program alumniachieve about the Ph.D. CeMM Ph.D. Program as well as publications remain. To publications well as as remain. honor their Commemorate andCelebrate graduated: Abdelghani Mazouzi (Loizou Group), (Loizou ­graduated: Abdelghani Mazouzi group of nine students in 2006 – 11 years later, group years of nine in2006–11 students group, to and year aQRcode graduation leading isrepresented on students an our graduated cally as well as personally –and memories great personally well as as cally individual Each ­completed studies. their Ph.D. - scientifi contributed – significantly has ­student fully ­fully - “promotio awarded by President sub auspiciis” Alexander Van To der Bellen. sub graduate Ultimately, CeMM on theof successes reflecting University of Cambridge, or Karolinska Institutet Institutet or Karolinska of Cambridge, ­University Harvard University, Mount Hospital, Sinai One of these graduates, Barbara Mair, received Mair, received Barbara ofOne these graduates, Ph.D. students during their also time at CeMM during students Ph.D. Medical School, Johns School, Hopkins University, ­Medical In 2017 we welcomed intoIn 2017 thestudent 100th perfect academic record academic since school, high ­perfect 20% continue­ physician- as do to research raises the questionraises of what they do and where from various non-M.D. backgrounds continue non-M.D. various from 10th –every disciplines many different from Stanford suchrenowned institutions as research positions inworld- garnering step, career next anew positionhave taken since their time with ­happy inspiressomany of CeMM that see to We leaving CeMM. very are after research while 74% move a to in Austria, stay CeMM paths of our the career we analyzed tive numbers, representa Using sufficiently they go afterwards. the highest possible honor citizen anAustrian future steps proudly. steps future and we considerresearch thisconfirmation of their careers inindustry, while anoverwhelming their careers theto clinic work to inthisprofession, while hail at CeMM students nameto afew. The Ph.D. CeMM is successful when itcomes priming to issuccessful CeMM program, in 2018 the 50th Ph.D. student will will student the 50thPh.D. in2018 the program, fact that education for Ph.D. students at students education that for Ph.D. the fact auspiciis, a student is required to have had a have to isrequired had astudent ­auspiciis, 86% take a postdoctoral position inacademic apostdoctoral 86% take and more years pass, we continueand more pass, appreciate to years fiil ceremony. ­official graduate within a given time frame and possess and possess withinagiven time frame ­graduate graduates. 26% of the former Ph.D. students who students 26%of the Ph.D. former graduates. our ­ graduate from CeMM. As CeMM keeps growing CeMM As CeMM. from ­graduate ­exceptional We achievement. to thrilled were isatruly This moral character. exemplary celebrate this special day with Barbara at the withBarbara day celebrate thisspecial for receive achievements academic can –the every individual student and will follow and student will individual their every scientists. 14% of the Ph.D. students who students come of the Ph.D. 14% scientists. doctor. 80%of isamedical them­student return students forstudents career. anacademic different country. leave 32%even ­different Europe for their students to continue to students inthe field of academic -

Ce — M­—M­— Research Report 2017 Facts 150 151 Catalyst Inc.,USA Anna Beninger,

“Why Diversity Matters: A Win-Win for AWin-Win Matters: Diversity “Why To the help profile raise of thegender equality wanted to know to ­wanted consent about informed in not at anissue CeMM. was Anna Beninger from ­ from Beninger Anna Ulrike Felt, ­ Felt, Ulrike On March 15, 2017, CeMMies greatly benefited greatly CeMMies 2017, 15, March On Institutions and Individuals”, was very well very was and­Institutions Individuals”, received by CeMM’s researchers. Our directors directors Our researchers. byreceived CeMM’s field and­ a is one of the most influential intheprofessors you’ve always entitled: “What atalk from havemight previously believed diversity that those who attend to –especially researchers on January 27, 2017. Her talk, entitled talk, Her 2017. 27, on January CeMM biomedical research: the story of a shifting of ashifting the story ­biomedical research: Studies at the University of Vienna. Prof. Felt of Vienna. at the University Studies

Responsible Research Lectures and promote to inacademia. ­science gender equality in about diversity awareness increase project aimsto The Libra and for essential important are allscientists. that skills ­practice; and good scientific integrity of research about allaspects our staff inboth and ethics compliance.standards includes This educating theThe highest Responsible project commits fostering to Research and way. behaviors ultimately change to inalasting attitudes, change subsequently among awareness to scientists, the goal raise isto Initially,change. iscommitted influencing to CeMM high. ­aiming projectare Both the Responsible projectand the Libra Research Patient Consent:Ulrike Felt Diversity: AnnaBeninger concept and practice”. This talk was given by was talk This ­concept and practice”. strongly ­ discussion at CeMM, we invited gender expert we invited gender expert at CeMM, discussion supported the all event and encouraged senior policy adviser in Europe. senior adviser inEurope. policy Professor of Science and TechnologyProfessor of Science Catalyst Inc., USA to to USA Inc., Catalyst “Incorporating Sex and Gender Aspects into and GenderAspects Sex “Incorporating Research”. This lecture was organized in organized was your lecture This Research”. On December 15, 2017, Sabine Oertelt-Prigione, Sabine 2017, 15, December On Research seminar at CeMM with her talk entitled withher talk at CeMM seminar Research Professor of Gender in Primary and Transmural Professor of Genderin Primary in the Netherlands, gave the sixth Responsiblein the the Netherlands, sixth gave Care at the Radboud University Medical Center Center Medical University at the Radboud Care aim of the lecture was to increase awareness awareness increase to was the aim of the lecture Sabine Oertelt-Prigione Sex andGenderinResearch: and gender dimensions into research. of of sex at the CeMM integrating importance connection also with the LIBRA project, and project, ­connection alsowiththe LIBRA institutes involved­institutes inLibra. ­produced for implementation the across a comprehensive guideline recruitment was the workshop, from Resulting and transparent. more process make the inclusive recruitment advice on how their practical to shared experts knowledge, our Using their research-based and ininterviews. fairly, both candidates on paper evaluate to injob advertisements and techniques language inthe ­ of diversity included program the importance The detailed Germany. of Mannheim, at the University of Econometrics at the Chair Manager ­Project Lübke, and Eva UK, Institute, Trust Sanger SWANAthena Wellcome Manager, Project Ahmed, Saher USA, Inc., at Catalyst Research Beninger, Director, Anna recruitment: ­unbiased of guided the through intricacies us experts Three theand optimal selecting candidate. for identifying and practice best recruitment into insights the­valuable topic of unbiased in the workshop, which provided and training participated institutes partner allLIBRA from HRrepresentatives Processes”. Recruitment ­workshop inGender-Inclusive Practice on “Best a organized CeMM 2017, 26, January On Recruitment Workshop of research. and balance and sex genderlife dimensions development be career work-will and training, project topics covered by the LIBRA ­Further without gender bias. recruit to activities ized central LIBRA’s coordinates Berlin, Medicine, Delbrück forwith the Center Max Molecular in­ CeMM, excellence sciences. inlife group, promoting ofall members the EU-Life countries, European ten from institutes research Itinvolves sciences life inacademia. ten equality achieve centres to gender research ­European innovative of efforts aimof unifying the stated H2020projectwith isanEC-funded LIBRA Activities Libra workplace, the crucial roleworkplace, of the crucial collaboration - childcare costs. costs. childcare of some work-related deductibility and the tax rules) of (inaccordance achild with new Austrian birth leave after paternity special newto parents, brochure with ­ a detailed includeures help ­ withfinding Meas leave. parental from returning ­scientists We have implemented ­ aprogram other have developed. alsobeen activities various ­ withthe Libra on our experience Building at large. and society in science groundswell equality relatedto about the current and develop to ­gender awareness and diversity out any challenge to ­ set by Vanja and Loizou Joanna ­lecture Nagy A of and sex gender­importance inresearch. among the of new intake of students the awareness include to raising in2017 ­further expanded was Program Introductory our Ph.D. commitment of CeMM’s part Libra, to As research. ­academic leadership role in asuccessful goal of attaining developed support to was withthe scientists and networkingboth components, training which involved The program, institutes. EU-Life ment workshop other alongside from postdocs career develop Libra won places attend to the first postdocs CeMM two inParis, 2017 June 13, On Other Activities forletters bias. reference and external) (internal evaluate to start We also threat. can environment for stereotype and tests We our interviews, now assess can examined. isbeing of process the recruitment of analysis allsteps Statistical procedures. hiring of our aspects detailed at certain more carefully look to ideas the administrationgave further The workshop performance. academic assessing and objectively vitae appraising curriculum like tactics We and combat it. nize alsodiscussed tools us recog to and gave bias our unconscious the workshop academia, from helped examine us reports and evidence-based studies case various media, ideal choice. Using examplesmass from an was she and universities, researchers ­scientific working experience togetherher with extensive to Due UK. Limited, Consultancy Challenge given Otitoju by from Femi bias unconscious on of leaders the and subject team for faculty Wednesday,On we held workshops 11, October Unconscious BiasWorkshops preconceptions about useful resources relevant resources useful suitable childcare, childcare, suitable targeted at targeted project, project, - - ­

Ce — M­—M­— Research Report 2017 Facts 152 153 + + of the Past Years: and TechnologyResearch TransferHighlights inthisrespect. partners and pharma a few, industry have valuable been &Dohme, name to and Sharp Merck Addgene, Ingelheim, Diagenode, Boehringer Qiagen, transfer. involving know-how, consultancy, technology and the out-licensing of patents or partnerships ment of the portfolio of companies, existing founding of companies, new start-up the enrich employees of­ideas CeMM’s inthe result can projects and the innovative itsresearch from arising Portfolio. opportunities Business ­Property Intellectual of CeMM’s commercialization and management inthe generation, Directors and the CeMM the researchers Munich assist Vossius from &Partner experts Patent ­patenting. of issues and conceptual on the practical staff itsscientific to trainings regular offers CeMM responsibility. of its societal output part itsresearch isanintegral ­valorizing and therefore, considers safeguarding that CeMM, promise have to animpact on medicine. and that initiatives support translational identify component isto An integral strategy of CeMM’s Transfer Technology Medicine (doi: 10.1056/NEJMoa1311347). Medicine of­published Journal England in the New have been findings The patients. CeMM MPN and brought anew ­ MPN of pathogenesis in thethe molecular gap This ­cases. about of 15% myeloproliferative neoplasia responsible­genetic for mutation (CALR) able been decode to a has CeMM of Vienna, ­ In collaboration withthe Medical 3026(17)30208-9). ­ Lancet The been publishedhas in trial ­first-everclinical of analysis the The interim their treatment. for patient anindividual at agiven time in options (single orchemotherapy synergistic) therapeutic the on determining – allwithafocus setting competencelogical inatranslational/medical hematological well and as as immuno­analysis, cell behavior,individual computational combines that CeMM high-content of imaging isamethodPharmacoscopy developed at newly identified newly mutation filled (doi: 10.1016/S2352- Haematology of hundreds­value thousands to of diagnostic kit to many kitto diagnostic University University - - [email protected] Ender: [email protected] Anita of CeMM, the Director Administrative contact please Formore information, lational activities. and trans for commercialization ­partnerships more even build andto sustainable strategic companies withseveral isincontact CeMM www.allcyte.com candidates. drug and promising indications for their drugs companies the most identify pharmaceutical right patients for the and drug right find the by helping physicians services ­decision-making development drug pre-clinical and clinical supports Allcyte high-content platform, imaging “pharmacoscopy” the so-called With ­material. human inprimary testing drug on functional Allcyte www.myelopro.com (CALR). the calreticulin protein called of the form mutated target that antibodies on the development focuses research Pro’s of myeloproliferative Myelo neoplasms (MPNs). forpeutics the­ treatment of blood diseases/ company, develop to aiming innovative thera MyeloPro www.haplogen.com diseases. of inthe­therapeutic programs area virus-caused apipeline Haplogen isbuilding of host factors, identify to genetics technology ­proprietary Employing a disease. ­combating infectious with the mission improve to human health by Haplogen develop and further to apply results: itsresearch of thepartner following spin-off three companies licensing agreements and isafounding several has holds about patent currently 10 families, CeMM is abiotech company start-up focused is a research stage biopharmaceutical biopharmaceutical stage is aresearch is a biopharmaceutical companyis abiopharmaceutical ­ - - tion between basic researchers and clinicians. and clinicians. researchers basic tion between itsmission, close which collabora requires fulfill complex, location is inaprime to CeMM research medical largest Austria’s Within years. the past in have established been importance ­strategic common projects of technologies. Several edge centered around cutting CeMM’s ­medicine on initiatives precision for research modern back ­ ments of innovation withatradition goes that of wide humantreatment ail range of avery competent in organization, dynamic research ­therapeutic approaches. The MUVisahighly and develop to and innovative diagnostic new into insights humangain pathophysiology to biological expertise withclinical processes on fundamental research needs and integrates isstrongly medical towards oriented research CeMM’s ment and students of faculty. CeMM and playsCeMM akey role develop inthe career of of partners the most research important (MUV)isone of Vienna University The Medical The MedicalUniversityof Vienna of Europe. inthe heart medicine ­precision and akey player and for biomedical research of the Academy institute aflagship made CeMM of itsoutput have already and the sustainability itspotential for of innovation, itsscience, ­quality The and biomedical basic through research. of human diseases the understanding advancing inter foundedinitiative, an in2005as was CeMM forward- move withadecisive into new impetus gained the ofbeginning Academy the new millennium, the At allover Austria. located and support staff scientists employing institutions 28 research 1,450 Itconstitutes of Vienna. heart inthe very building inthe impressive oldheadquarters university its The Academy has and political spectrum. ­public the across business and decision-makers to the to ofby their expertise making broad range application, supported by itsmembers ­practical much of whichresearch, isdeveloped into ­economic itconducts basic responsibilities, and cultural of itssocial, Cognizant Austria. in organization research academic university” ­developed “non- become to the pre-eminent, since the Academy society, has alearned as Founded in1847 Academy of Sciences. ­Austrian of the institute isaconstituent ­Medicine, for Center Molecular the Research CeMM, Austrian AcademyofSciences Collaborations and Partnerships Strategic disciplinary research institute committed to institute research ­disciplinary centuries. It provides a perfect environment Itprovides aperfect centuries. looking areas of research. As part of this part As of­looking research. areas - - - rud.lbg.ac.at www.eu-life.eu www.meduniwien.ac.at www.oeaw.ac.at diseases. of rare economical aspects and ethical but societal, address alsoto future, of the medicine and personalized precise of the participatory, part as andtics therapeutics The goal of contribute isto diagnos to LBI-RUD of muchunderstanding more diseases. frequent intoinsights human biology and add our to alsoprovide therapies; itwill novel­targeted and provide individuals for the basis affected not will only berelevant research theThis to account for more diseases. 50%of than allrare which alltogether system, and the nervous of the hematopoiesis immune system, diseases ison rare Boztug under the leadership of Kaan of the LBI-RUD focus The research ­LBI-RUD. of the part which anintegral are ­Hospital, Children’s Anna of the St. (CCRI) Institute Research Cancer and the Children’s of Vienna, University ­conjunction the Medical withCeMM, in by the Ludwig Boltzmann Gesellschaft founded was (LBI-RUD) Diseases Undiagnosed and forThe Ludwig Rare Boltzmann Institute LBI-RUD broader community. joint either for the activities, network or for a and theydefine design best andpractice share working setup dedicated which groups, partners the goals, To forward. EU-LIFE reach ­science European with aviewpushing to sciences, life knowledge in policy and influenceresearch joined complex forces address to questions, share the partners alliance landscape, national research ahighly competitive Within inter perspective. ­competitiveness and withthe international same independence, reviews, excellence, external ofall of principles whom withsimilar operate inSwitzerland, for Research Biomedical ­Institute Miescher and the Friedrich (NKI) ­Institute the Netherlands inBelgium, Cancer (VIB) for Biotechnology Institute the Flanders Spain, the for Centre Genomic Regulation (CRG) in include, for example, Other partners partners. one of the was founding CeMM scientists). 7,200 groups, 13 renowned (~500research centers of Itisanalliance ­excellence inlife-sciences. set up support European to and strengthen isapartnership in2012, established EU-LIFE, EU-LIFE

- -

Ce — M­—M­— Research Report 2017 Facts 154 155 and ­ their We opinions from learn pages. believe we can that ­testimonials presented are inthe inthe following past The photographs of those who their have imparted ­ ­artists, ­ ­government, included holders of prominent positions in both advisors and and of have supporters CeMM people These are reports. in our research annual whichphilosophies we include and performance, invite notable people on CeMM’s their give to take us to tradition successful along been andIt has so-far Supporters benefit from theirbenefit approval andencouragement. comedians and a sporting World andcomedians asporting Champion. industry and academia, accomplished and academia, industry Republic and former Commissioner of the City of Vienna Prof.Bellen Dr. der Van Alexander Chairwomen of theScience Center Network Foundation Margit Fischer Institute of Molecular Biotechnology (IMBA) Prof. Dr. JosefPenninger Scientific Director,

President of the ­ Austrian and Technology Austria, Klosterneuburg Professor Dr. GaiaNovarino Instituteof Science President of the Austrian Academy of Sciences Prof. Dr. AntonZeilinger Artist Eva Schlegel Medical Director of the Vienna General Hospital Prof. Dr. Gabriela-Verena Kornek Particle Physicist, CERN, Geneva Dr. Fabiola Gianotti

Ce — M­—M­— Research Report 2017 Facts 156 157 Chief Executive Officer of Evotec AG Dr. Werner Lanthaler, MBA,MPA and Chief Technology Officer, Infineon Technologies Austria AG Dipl. Ing.Dr. SabineHerlitschka, MBA Chief ExecutiveOfficer Artists Walking Chair

National Library, Member of theSenate of theÖAW and ­ Professor Dr. Veronika SexlInstituteof Pharmacology Dr. JohannaRachinger Immunobiology, Yale Schoolof Medicine, USA Prof. Dr. Richard Flavell Toxicology, University of Veterinary Medicine, Vienna Director General of the Austrian Sterling Professor of Rector, Medical University of Vienna Prof. Dr. MarkusMüller Artist Brigitte Kowanz Faculty of Physics, University of Vienna and VCQ Prof. Dr. Markus Aspelmeyer Former Member of theExecutiveBoardof Siemens AG Mag.ª BrigitteEderer Artist Peter Kogler Section for Natural Sciencesof theÖAW Prof. Dr. GeorgStingl Former Presidentof the

Dana-Farber/Harvard Cancer Center, Boston Prof. Dr. DavidLivingston of Vascular ­ Prof. Dr. BerndBinder†Department Biology and Thrombosis Research, MUV Deputy Director,

City Councilor for Culture and Science, Vienna Dr. Andreas Mailath-Pokorny ­Belvedere Palace Museum and 21er Haus Dr. AgnesHusslein-Arco Medical University of Vienna Prof. Dr. Josef Smolen Headof Division of ­ Former Federal Minister for Education Dr. SonjaHammerschmid Former Director of the Rheumatology,

Ce — M­—M­— Research Report 2017 Facts 158 159 National Council, Member of theSenate of theÖAW Mag.ª Barbara Prammer †Presidentof the Austrian ­Officer, Infineon Technologies Austria AG Mag.a MonikaKircher-Kohl Former Chief Executive

Archbishop of Vienna Cardinal ChristophSchönborn Former Director, Institute for Advanced Studies, Vienna Prof. Dr. Bernhard Felderer Artist Dorothee Golz Comedians, TV Stars, Compères “Willkommen ­ Stermann &Grissemann Österreich” Patient Advocate of the City of Vienna Dr. SigridPilz Former Austrian Federal Minister of Science and Research Dr. BeatrixKarl Former Vice Presidentof theEuropeanParliament Ulrike Lunacek Regenerative MedicineInstitute, Melbourne Prof. Dr. Nadia Rosenthal Former Presidentof the Austrian Academy of Sciences Prof. Dr. HelmutDenk Univ., SE, Chairman Boardof theNobel Foundation Prof. Dr. Carl-Henrik Heldin Director, Australian Director, LICR,Uppsala

Artist Thomas Feuerstein of Pediatrics and Adolescent Medicine, MUV Prof. Dr. Arnold Pollak Former Headof theDepartment Former Presidentof the Austrian Republic Dr. HeinzFischer and interimPresidentof the Austrian ScienceFund Prof. Dr. ChristineMannhalterFormer Vice-President Commissioner of theEuropeanUnion Dr. JohannesHahn

Ce — M­—M­— Research Report 2017 Facts 160 161 Boehringer Ingelheim RCV Vienna Philipp vonLattorff and Scientific Director of the Vienna Cancer Center Prof. Dr. ChristophZielinskiDirector of the CCC Vienna Ambassador of Italy totheRepublic of Austria Giorgio Marrapodi Country ManagingDirector and Mathematics at Harvard University Prof. MartinA.Nowak, Ph.D. Professor of Biology Former Rector, Medical University of Vienna Prof. Dr. Wolfgang Schütz Sponsors Dr. BenediktandBeatriceSpiegelfeld Federal Minister of Science, Research and Economy Dr. Reinhold Mitterlehner Former Director of the Vienna General Hospital Prof. Dr. Reinhard Krepler Former Presidentof FWF and ÖAW Prof. Dr. Hans Tuppy Former Federal Minister, Former Vice-Chancellor and and Former President,EuropeanResearch Council Prof. Dr. HelgaNowotnyPh.D. Founding Member Former Ambassador of theUnitedKingdomto Austria Susan leJeuned’Allegeershecque

F1 World Champion and Airline Founder Niki Lauda St. Anna Children’s Cancer Research Institute Prof. Dr. HelmutGadnerFormer Director, social satire role as the(fictitious) AustrianEmperor Robert Palfrader Austriancomedianinhismostfamous President of theFederation of Austrian Industries Mag. GeorgKapsch Former Austrian Federal Minister of Science and Research Prof. Dr. Karlheinz Töchterle Mayor of the City of Vienna Dr. MichaelHäupl Artist Esther Stocker

Ce — M­—M­— Research Report 2017 Facts 162 163 and Technology DevelopmentSenator, ÖAW Governor OesterreichischeNationalbank Prof. Dr. EwaldNowotny Dr. HannesAndrosch MUV ÖAW AKH

Vienna General Hospital Medical University of Vienna Austrian Academy of Sciences Chair, Austrian Council for ­

Research Former Presidentof the Austrian Academy of Sciences Prof. Dr. Peter Schuster of Ophthalmology and Optometrics at theMUV/AKH Prof. Dr. UrsulaSchmidt-ErfurtHeadof the­ Rector, Vienna University of Economics and Business Professsor DIDr. Edeltraud Hanappi-Egger Department Artist Martin Walde Winner of theNobelPrizefor Medicine2008 Prof. Dr. Harald zurHausen the ­ Prof. Dr. MaxL.Birnstiel†Founding Director of Research Instituteof Molecular Pathology (IMP)

www.cemm.at [email protected] Tel +43-1/40160-70 011 1090 Vienna, Austria Floor Main Entrance, 1st Lazarettgasse 14, AKH BT 25.3 of theAustrian AcademyofSciences Research CenterforMolecularMedicine CeMM CeMM Reach to How Borschkegasse

W ä hr in g e Main Entrance r G ü r te l Tower Green South Entrance

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Facts 164 165 Philippe Cronet Matthew Crawford Patrick Cramer Francesca Ciccarelli Riki Cheever Emmanuelle Charpentier Claudia Caserini Georg Casari Jakob Calice Meinrad and IreneBusslinger Erhard Busek Jürgen Busch Jo Bury Günther Burkert Jörg Bürger Bruno Buchberger Oscar Bronner Georg Brasseur James Bradner Peter Brabeck-Letmathe Jean-Pierre Bourguignon Günther Bonn Stefan Böhm Martin and LucreziaBöhm Guido Boehmelt Bruno Biton Margret and Kristy Birnstiel Binder and ChristaBernd Andreas Bichl Andreas Becker Stephan Beck Hemma Bauer Angela Bauch Ralf Bartenschläger Denise P. Barlow Alexandra Augustin Gertraud Auer Boread'Olmo Patrick Auer Markus Aspelmeyer Anna Artaker Cheryl Arrowsmith Stylianos Antonarakis Raul Andino Gustav Ammerer Michael Alram Alma Adriano Aguzzi Acknowledgements Hermann Hauser Eric Haura Michael Häupl Edeltraud Hanappi-Egger Markus Hanakam Sonja Hammerschmid Bradford S.Hamilton Barbara Hamilton Johannes Hahn Bernhard Groehs James D. Griffin Susanne Greber-Platzer Dorthee Golz Christoph Gnant Laurie Glimcher Wolfgang Gleissner Heinz Gisslinger Fabiola Gianotti Daniel Gerlich William Gahl Helmut Gadner Julia Fröhlich Michaela Fritz Michael Freissmuth Bert Fragner Richard Flavell Heinz undMargit Fischer Thomas Feuerstein Ulrike Felt Bernhard Felderer Heinz Fassmann Harald Esterbauer Michelle Epstein Heinz Engl Traudl Engelhorn Wilfried Ellmeier Titanilla Eisenhart Hans Georg Eichler Alexander Ehrmann Hubert-Christian Ehalt Henrietta Egerth Aled Edwards Gerhard Ecker Stefan Echinger Katharina L.Dürr Darren Dumlao Christiane Druml Ivan Dikic Daniela Digles Helmut Denk Nicolas Demaurex Thomas Decker Jan de Vries George Daley Olli Kallioniemi Wolfgang Kainz Andrea Kainz Ulrich Jordis Kai Johnsson Erika Jensen-Jarolim Sigrid Jalkotzy-Deger Ursula Jakubek Ulrich Jäger Harald Isemann Ad P. IJzerman Monika Hutter Lukas Huber Barbara Horejs Andrew Hopkins Volker Hölzl Wolfgang Holter Denis Hochstrasser Helen Hobbs Gottfried Himmler Sabine Herlitschka David Hepworth Thomas Henzinger Markus Hengstschläger Thomas Helleday Carl-Henrik Heldin Laura Heitman Franz Xaver Heinz Claudia Heilmann Karl-Heinz Heider Hans Kupelwieser Ernst Kriehuber Reinhard Krepler Michael Krebs Norbert Kraut Christoph Kratky Dietrich Kraft Peter Kowalski Salome Koussoroplis Liechtenstein Maria PiaKothbauer- Gabriele Kornek Ernst Kopper Peter Kogler Reinhart Kögerler Christian Köberl Uta Knittel Stefan Knapp Christoph Klein Markus Kiess Dontscho Kerjaschki Claudia Kemper Janet Kelso Douglas B. Kell Annie Kay Beatrix Karl Georg Kapsch Martin Moder Reinhold Mitterlehner Michael Metzeltin Jürgen Meier Karl Mechtler Lamine Mbow Brigitte Mazohl Marjori Matzke Iain Mattaj Herbert Matis Giorgio Marrapodi Vania Manolova Christine Mannhalter Herbert Mang Rudolf Mallinger Andreas Mailath-Pokorny Harald Mahrer Dieter Lutz Ulrike Lunacek Friedrich Lottspeich Daniel Löcker David Livingston Claudia Lingner Stefanie Lichtwitz Maria Leptin Kriso Leinfellner Klaus Lechner Niki Lauda Hans Lassmann Werner Lanthaler Paula Nunes-Hasler Helga Nowotny Martin A. Nowak Martin Nowak Gaia Novarino Elisabeth Nöstlinger Magnus Nordborg Waltraud and LaurenzNiel Michael Nentwich Bhushan Nagar Johann Mulzer Markus Müller Maria Mota Thomas Moser Szymanski Witold and Claudia Peter Swetly Arnold Suppan Stefanie Superti-Furga Michela Stucchi Esther Stocker Moritz Stipsicz Georg Stingl Dirk Stermann Claire Steppan Michael Stampfer Almuth Spiegler Spiegelfeld Beatrix and Benedikt Michael Speicher Josef Smolen Uwe Sleytr Timothy Skern Michael Sixt Jörg Simonitsch Sabine Simmross Maria Sibilia Veronika Sexl Klaus Seuwen Luis Serrano Dieter Schweizer Bertram Schütz Wolfgang Schütz Roswitha Schuller Renée Schröder Cardinal Christoph Schönborn Georg Schneider Ursula Schmidt-Erfurth Andreas Schibany Hubert Scheibl Gerhard Schadler Lia Scarabottolo David Sabatini Paul Rübig Nadia Rosenthal Artur Rosenauer Achim Ribbe Jürgen Reinhardt Kurt Redlich Loredana Redaelli Meinrad Rauchensteiner Frédéric Puech Christoph Prammer Barbara Prainsack Jeff Porter Maria Polsterer-Kattus Arnold Pollak Helmut Pockberger Hidde Ploegh Karl EmilioPircher Sigrid Pilz Helen Pickersgill Klaus Pichler Fidel Peugeot Jan-Michael Peters Josef Penninger Primus Österreicher

Harald zur Hausen Elke Zuckermann Johannes Zschocke Marcus Zobl Christoph Zielinski Anton Zeilinger Rudolf Zechner Oleh Zagrijtschuk Nikolaus Zacherl Klaus Wolff Hans Wojta Joseph Witztum Anke Wittig Maria Wilhelm Georg Wick Wolfgang Weninger Werner Welzig Barbara Weitgruber Manfred Walkobinger Werner Waldhäusl Martin Walde Oswald Wagner Philipp von Lattorff Isabelle Vernos Alexander van der Bellen Peter Valent Alfonso Valencia Hans Tuppy Maja Tumpej Michael Trauner Thomas Töller Klement Tockner Karlheinz Töchterle Daniela Thommen The Vienna English Theater The DublinLegends Werner Telesko Klaus Taschwer Elly Tanaka Herwig Tachezi

Ce — M­—M­— Research Report 2017 Facts 166 167 Copyrights Research Report 2007 Research Report 2008 Research Report 2009 © CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria www.cemm.at

Overall responsibility for content Giulio Superti-Furga, Ph.D. Scientific Director CeMM Anita Ender Administrative Director CeMM

Editors Eva Schweng, MAS PR Manager CeMM Wolfgang Däuble Media Relations Manager CeMM 2007 2008 2009

Science Writer CeMM Research Report 2011 Wolfgang Däuble

Research Report 2010 Art Direction and Design Lichtwitz Leinfellner visuelle Kultur KG Kriso Leinfellner Stefanie Lichtwitz Rita Atteneder

Photography Belle & Sass (pp. 118–119, 122 Roland Ferrigato (p. 106) Thomas Fröhle (p. 164) MedUni Vienna/

Martin Hörmandinger (p. 127) Research Report 2012 Sharona Jacobs (p. 162) Hans Leitner (p. 85, 163, 107) 2010 2011 2012 fnung_allgemeinMutationA fnung_allgemeinMutationB fnung_detailHuelle_leer fnung_detailMutationA fnung_detailMutationB fnung_allgemeingeschlossene_Form fnung_allgemeinHuelle Claudia Marcelloni (p. 157) fnung_detailgeschlossene_Form fnung_detailHuelle_gefuellt oluminoesflach.voluminoes oluminoesvoluminoes oluminoesflach AehnlichkeitAehnlich_PX34 Position_allgemeinhaengt Aufbau_detailgenaeht_gefuellt FarbeFarbe_X Farbehellgruen FarbbasisMaterialfarbe Farbkombinationblau.orange Generation5 BruderpaarBruder_PX42 BruderpaarBruder_PX92 Groessegross Position_detailsteht Aufbau_detailgebaut_gefuellt Farbkombinationgrau.milch Zweites_MaterialHolzkiste Zweites_Materialnein Einsatz_allgemeineinfach Einsatz_detail1Einsatz_Ausguss Einsatz_detail1Einsatz_M1 Einsatz_detail1Einsatz_M4 Einsatz_detail1Einsatz_Schlauch Einsatz_detail1nein Einsatz_detail2Einsatz_Glas 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FormmerkmalKombination HalbkugelHalbkugel Konvexkonvex V StrukturRillen Generation2 BruderpaarBruder_PX46 AehnlichkeitAehnlich_PX54 MaterialPlastik Farbeunbekannt FarbbasisMetallbeine Farbkombinationnein Farbkombinationweiss.milch Zweites_MaterialPVC.Folie Einsatz_detail1Einsatz_Glaslinse Einsatz_detail1Einsatz_Noppen Einsatz_detail1Einsatz_Staender Einsatz_detail2Einsatz_Mutation Einsatz_detail2nein IronieIronie Biomorph_detailbiomorph_andere Biomorph_detailbiomorph_tailliert Schnorchel_allgemeinSchorchel Schnorchel_detail1nein Schnorchel_detail1Schnorchel_schmal Schnorchel_detail2Schnorchel_Aufsatz Schnorchel_detail2Schnorchel_Metall Schnorchel_detail2Schnorchel_rund DUO_Gruppesingle Oe f Oe f Formmerkmal2_Spoiler FormmerkmalHoehle Formmerkmalmittiger_Einsatz Formmerkmalnein Formmerkmal Gereihteinfach Gereihtgereiht Gereihtnein Konkavkonkav Konkavnein Oberflaecheglatt Oberflaechestruktur StrukturMuta1 Strukturnein StrukturNoppen Beinenein Zusatztitelja PX1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX3 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX4 1 1 1 1 1 1 1 1 1 1 1 1 Klaus1 Pichler1 (pp.1 1 10,1 13, 16–17,1 24–25,1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX5 1 1 e 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX6 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX7 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX8 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX1 1 1 1 1 1 1 1 1 1 1 1 36–37,1 1 44–45,1 52–53,1 1 78–79,1 103,1 110–117,1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX12 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX13 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX14 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX15 1 1 1 1 1 1 1 1 1 1 1 1 125, 1150) 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX16 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX17 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX18 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX19 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX21 1 1 1 1 1 1 1 1 1 1 1 Iris1 Ranzinger1 1 (pp.1 1 157, 158, 1 159, 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX22 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX23 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX24 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX25 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX26 1 1 1 1 1 1 1 1 1 1 1 1 160,1 161, 163,1 164)1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX27 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX28 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX29 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX3 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX31 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX32 1 1 1 1 1 1 1 1 1 1 1 Michael1 1 Sazel1 (pp.1 1 68, 80–1 81, 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX33 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX34 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX35 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX36 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX37 1 1 1 1 1 1 1 1 1 1 1 1 88–95,1 98–99)1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX38 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX39 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX41 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX42 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX43 1 1 1 1 1 1 1 1 1 1 1 1 Ludwig1 Schedl1 1(pp.1 61– 62, 1113–117)1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX44 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX45 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX46 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX47 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX48 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX49 1 1 1 1 1 1 1 1 1 1 1 Giulio1 1 Superti-Furga1 1 1 (pp. 96–97)1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX51 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX52 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX53 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX54 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX55 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX56 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX57 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX58 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX59 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX6 1 1 1 1 1 1 1 1 1 1 1 1 Cover1 by CeMM1 1 faculty1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX61 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX62 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX63 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX64 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX65 1 1 1 1 1 1 1 1 1 1 1 Blue1 1Book Challenge1 1 1 by 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX66 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX67 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX68 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX69 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX7_neu 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX71_neu 1 1 1 1 1 1 1 1 1 1 1 CeMM1 1 community1 1 1 (pp.1 5–8) 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX72 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX73 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX74 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX75 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

PX76 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

All other photos by CeMM 0 PX77 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2

PX78 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 t

PX79 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 r 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX8 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 o 1 1 1 1 1 1 1 1 1 1 1 1 1 1 p PX81 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 R e

PX82_neu 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX83 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX84 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX85 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX86 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

PX87 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 R esearc h 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX88_neu 1 1 1 1 1 1 1 1 1 1 1 1 Walking1 Acts1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX89 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX9 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Research1 Report 201 1 1 1 1 1 1 1 1 1 1 1 Research Report 201 PX91 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Research Report 201 PX92 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX93 1 1 1 1 1 1 1 1 1 1 1 1 Wolfgang1 Kainz1 1 (director),1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX94 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX95 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX96 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PX97 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 frei_A 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 frei_B 1 1 1 1 1 1 1 1 1 1 1 1 Maria1 Lohn, 1Julia1 1 Lotz, Megan1 Crain1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 140702_Umschlag_zickzack_RZ.indd 1 03.07.14 13:01 entil V ariation Farberot ertiefung Ironienein Beinenein Farbeblau Farbegelb Farberosa Haptikhart Farbebunt Farbegrün Farbegrau Sockelnein Farbemilch IronieIronie BeineBeine Farbeweiss Gereihtnein Konkavnein Farbegruen Konvexnein Haptikweich Zusatztitelja Strukturnein Generation3 Generation2 Generation4 Generation5 Generation6 Generation7 Generation1 MaterialGips Bezeichnung Groesseklein StrukturRillen SockelSockel MaterialPaste Groesseriesig MaterialBeton Biomorphnein Groessegross Groessemittel Aufbaugebaut StrukturMuta1 StrukturMuta2 StrukturMuta3 Farbeschwarz Halbkugelnein Gereihtgereiht Zusatztitelnein FarbeFarbe_X MaterialSilikon MaterialPlastik Gereihteinfach Konkavkonkav 2013 Konvexkonvex 2014 2015 oluminoesflach Farbehellgruen

Aufbaugenaeht Alan Burgon, Robert Neumayr, Farbbasisfabric Bruderpaarnein Aufbaulaminiert Wichtigkeithoch StrukturNoppen Farbeorange.rot Aehnlichkeitnein Farbeunbekannt Oberflaecheglatt Generationkeine MaterialPolyester Wichtigkeitnormal DUO_GruppeDuo Formmerkmalnein MaterialKunstleder FormmerkmalLoch Biomorphbiomorph FarbbasisPU.gruen Einsatz_detail1nein Einsatz_detail2nein Aufbauabgegossen DUO_Gruppesingle Position_detailsteht Oberflaechestruktur MaterialPapierpaste HalbkugelHalbkugel Farbbasisunbekannt Biomorph_detailnein Aufbau_detailgebaut Farbkombinationnein FormmerkmalHoehle Zweites_Materialnein DUO_GruppeGruppe FarbbasisMetallbeine FarbbasisFarbauftrag oluminoesvoluminoes fnung_detailMutationA fnung_detailMutationB Einsatz_allgemeinnein fnung_allgemeinHuelle FarbbasisSilikon.gruen FarbbasisMaterialfarbe Schnorchel_detail2nein Schnorchel_detail1nein Formmerkmal2_Spoiler BruderpaarBruder_PX8 fnung_detailHuelle_leer Position_allgemeinsteht BruderpaarBruder_PX42 BruderpaarBruder_PX92 BruderpaarBruder_PX35 BruderpaarBruder_PX46 BruderpaarBruder_PX89 BruderpaarBruder_PX81 Einsatz_allgemeineinfach Position_allgemeinhaengt Aufbau_detailabgegossen Zweites_MaterialPlexiglas Zweites_MaterialHolzkiste AehnlichkeitAehnlich_PX3 FormmerkmalKombination Schnorchel_allgemeinnein fnung_allgemeinMutationA fnung_allgemeinMutationB Einsatz_detail1Einsatz_M1 Einsatz_detail1Einsatz_M4 Einsatz_detail2Einsatz_NA Einsatz_detail1Einsatz_M2 Einsatz_detail1Einsatz_M3 oluminoesflach.voluminoes Farbkombinationgrau.milch Zweites_MaterialPVC.Folie fnung_detailHuelle_gefuellt Farbkombinationgelb.weiss AehnlichkeitAehnlich_PX34 AehnlichkeitAehnlich_PX41 AehnlichkeitAehnlich_PX43 AehnlichkeitAehnlich_PX44 AehnlichkeitAehnlich_PX45 AehnlichkeitAehnlich_PX46 AehnlichkeitAehnlich_PX47 AehnlichkeitAehnlich_PX53 AehnlichkeitAehnlich_PX54 AehnlichkeitAehnlich_PX58 AehnlichkeitAehnlich_PX63 Farbkombinationgrau.weiss AehnlichkeitAehnlich_PX14 AehnlichkeitAehnlich_PX29 AehnlichkeitAehnlich_PX32 AehnlichkeitAehnlich_PX73 AehnlichkeitAehnlich_PX77 Aufbau_detailgenaeht_hohl Farbkombinationgrau.gruen Farbkombinationweiss.milch Einsatz_detail2Einsatz_Glas Farbkombinationblau.orange Aufbau_detailgebaut_gefuellt Einsatz_detail2Einsatz_Metall Thomas Middler, Uta Knittel (costumes) Formmerkmalmittiger_Einsatz Aufbau_detailgenaeht_gefuellt Einsatz_detail2Einsatz_Plastik Aufbau_detaillaminiert_gefuellt Einsatz_detail1Einsatz_Noppen Schnorchel_allgemeinSchorchel Einsatz_detail1Einsatz_Ausguss Einsatz_detail2Einsatz_Mutation fnung_detailgeschlossene_Form Einsatz_detail1Einsatz_Staender Einsatz_detail1Einsatz_Glaslinse Einsatz_detail1Einsatz_Schlauch Biomorph_detailbiomorph_tailliert Biomorph_detailbiomorph_andere Position_detailhaengt_mit_Abstand Schnorchel_detail2Schnorchel_rund fnung_allgemeingeschlossene_Form Position_detailhaengt_ohne_Abstand Schnorchel_detail2Schnorchel_Metall Schnorchel_detail1Schnorchel_schmal Schnorchel_detail2Schnorchel_schmal Einsatz_detail2Einsatz_Schaumgummi Schnorchel_detail2Schnorchel_Aufsatz Print Druckerei Gugler Paper MultiOffset, 120g

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Eva Schweng CeMM Research Center for Molecular Medicine of the 2016 Austrian Academy of Sciences [email protected] Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria Tel +43-1/40160-70 051 Fax +43-1/40160-970 000 www.cemm.at