European Research Institute for the Biology of Ageing

Annual Report 2017 Annual Report 2017 Table of Contents

Foreword 6

Ageing Research at ERIBA 8

2017: A Closer Look 12

Facts and Figures 18 Table of Contents of Table

Scientific Publications 20 Table of Contents

4 www.eriba.umcg.nl Funding/Grants 26 5

Coordination: Gerald de Haan and Helena Rico

Secretarial Support: Invited Speakers 28 Sylvia Hoks, Nina Kool and Annet Vos-Hassing

Design and Illustrations: G2K Creative Agency People 32

Printing: Zalsman Grafische Bedrijven, Groningen

400 issues Education 36

Outreach and Dissemination 38

Scientific Advisory Board 41

Sponsors 42

6 Foreword

2017 review in Foreword and funding. and funding. education science, of terms in expand we should where indications thoughtful received and achievements overall our with complimented highly been have we encouragement: and enthusiasm great with We honoured were mance. perfor years’ five first our of review athorough conduct to asked were who (see 41) page scientists recognized internationally of (SAB), composed Board Advisory Scientific our by evaluated time first the 2017, in for we were Early of! proud be should us of each ajourney Again, levels. European and national at grants competitive highly and prestigious through funding external of amount asignificant We secured come. to years the in pursue to we want collaborations existing We new national and international alliances established and strengthened globe. the of parts many from students promising attracted and staff and scientists of team awonderful We recruited scratch. from Institute We an built tremendous journey. happy and proud to say that it has a been years since our doors opened in and 2012, Iam of Ageing.for the Biology has now It five been of theAnnual European Report Research Institute pleased to shareI am very with you the 2017 ­ very proud of. very a Rubicon Fellowship, which we are studentPhD has honoured been with the Dutch Cancer Society. Aformer award andVIDI multiple from grants In 2017 ERIBA scientists secured a http://eriba.umcg.nl/wp-content/uploads/2015/12/report-2012-2016.pdf here: available is Report 2012-2016 The 2018 January Director Scientific de Haan Gerald process. ageing the of aspects different of down slowing the allow that interventions molecular identify to contribute to continue will scientists ERIBA We that we age? do how believe ever: as relevant and solid remains mission Our studies. ground-breaking (and hopefully) high-risk pursue and grow to us enable would which funding, our increase year(s) further even to be next will the for challenge collective Our sources. extramural from originates budget our of ~80% ERIBA, In students. 5.000 over which attracted we age”, do “Why Course Online Open Massive the time fourth the for We re-ran world. the around from investigators young and scientists renowned well of number alarge of participation the with Meeting, Ageing of Biology Molecular the time second the for organized we successfully Furthermore, interns. more students, PhD more employees, more papers, excellent more news: good of Alot to. attention special draw to we want activities 2017 the of asummary provides Report current The (see below). link projects ongoing of compilation extensive an and ERIBA’s of avenues research description acomprehensive contains which Report 2012-2016 the We revisit to you invite

7

Foreword Ageing Research at ERIBA Ageing Research at ERIBA Ageing Research at ERIBA at Research Ageing

8 9 Genomic Instability in Ageing Research Development and Disease The long-term aim of the Laboratory of Floris Foijer and his team is understanding at ERIBA aneuploidy to improve cancer therapy.

Quantitative Epigenetics The group of Maria Nucleic Acids Structures Colomé-Tatché is interested and Repair in understanding the The particular focus of Katrin Paeschke epigenetic changes that Laboratory is to understand the nature and take place during the role of secondary structures that form processes of development, within nucleic acids. ageing and disease. Stem Cell Regulation and Mechanisms of Regeneration Genome Structure Ageing The Laboratory led by Research at the Laboratory of Victor Eugene Berezikov aims at Guryev is aimed at understanding Ageing Research at ERIBA Ageing is the major risk factor for many diseases, understanding molecular structural changes in human genomes for a including cancer, dementia and diabetes. The mechanisms that regulate better detection of genomic and regeneration and activity environmental risks as well as for mission of scientists in ERIBA is to prolong health. of stem cells. disease prevention. To do so, we study how ageing occurs in cells, Ageing Biology Asymmetric Cell and Stem Cells Division and Ageing

tissues, organs, and indeed, whole organisms. If we The aim of studies of Gerald Judith Paridaen and her group are ERIBA at Research Ageing understand how ageing happens, we can develop de Haan’s Laboratory is to focused on understanding how 10 understand the mechanisms microscopic processes within single stem 11 approaches to intervene in the ageing process. that specify normal cells affect their function which is hematopoietic stem cell essential to answer how stem cells Gene Regulation functioning from birth shape and can help to maintain There is no tissue in our body that is immune to ageing. In Ageing and to death. an healthy body. Nevertheless, exciting scientific discoveries have shown Age-Related Diseases that it is very well possible to intervene in the ageing The group of Cor Calkoven Genetic Instability and Ageing process. So, although ageing may be inevitable, it is also is particularly interested in the The role of genome instability modifiable. This is also seen in humans; some people age function of mRNA control in stem cells in relation to disease fast, whereas other age much slower and remain healthy till elements, protein factors processes and ageing is the main advanced age. and microRNAs that are focus of Peter Lansdorp group. involved in mTORC1- While ageing is associated with many distinct diseases and controlled processes. Cellular Senescence and affect all organs, we believe that molecularly ageing is Age-related Pathologies Cellular Biochemistry caused by only a limited number of things that go wrong: Marco Demaria’s Group The laboratory of Liesbeth Veenhoff “one cause, many problems”. Scientists in ERIBA therefore aims to understand the basic aims for a system wide global study the root cause of ageing, and find ways to intervene molecular and cellular characterization of age-related changes, as in them. mechanisms of ageing, well as detailed understanding how the particularly a specific NPCs and cognate transport factors ERIBA is currently the home of 13 research groups that Telomeres and cellular state, “senescence”. play a role in cellular ageing. cover a wide range of age-related topics. Genome Integrity Molecular Neurobiology The overall goal of Michal of Ageing Chang’s Laboratory is to The group led by Ellen Nollen is figure out the mechanisms focused on understanding the molecular used by a cell to protect its mechanisms that drive age-related toxicity genome from becoming of aggregation-prone proteins, which mutated or inappropriately plays a role in age-related diseases altered or rearranged. like Parkinson and Alzheimer. 2017 A Closer Look A Closer Look A Closer A Closer Look

12 13 14 Look Closer A

A Closer Look 2017 formation. formation. tumour spontaneous promote to sufficient is amplification centrosome that Cell Development in apaper in showed they labs collaborating other Floris Foijer with together example, an As come. to more with papers, joint multiple to led has and fruition full to come has analyses genetic cell single Peter Lansdorp that efforts the that see to great is It science. modern in essential is which spirit to collaborative the testifies This Center Groningen. Medical University the in scientists with scientists ERIBA of projects from or ERIBA, within of groups research resulted various from joint collaborative projects research papers these of many 25). to 20 importantly, pages More in list complete papers 55 of number arecord published ERIBA in scientists 2017 In Publications Scientific the various Laboratories of ERIBA throughout 2017. achievements that have accomplished been within number of aselected reports This section field. field. the in journal prime the BLOOD, for aging cell stem hematopoietic on review Lazare Seka and Haan de Gerald genesis in Mammals. Tumori­ Spontaneous Promote to Sufficient Is Amplification Centrosome F, AJ. D, Foijer DW, Holland Cleveland Lambrechts PM, Lansdorp DC, Spierings B, Vitre J, Lu J, Moyett B, Boeckx B, Bakker MS, Levine in press 2017, Blood cells. stem Aging hematopoietic of S. Lazare Gand Haan de

6;40(3):313-322.e5 Feb 2017 Cell. Dev , his PhD student, wrote an authorative authorative an wrote student, PhD , his and his group invested in in invested group his and (see (see and and identify the transcription factor C/EBP the transcription factor identify they which in Reports, Cell in apaper published Calkhoven Cor of lab The experiments. genetic vivo in sophisticated for allows now Communications), of which this animal, has achieved transgenesis and indeed Macrostomum lignano, organism, model favorite their Berezikov Eugene effects. anti-cancer have and mimetics restriction calorie as classify may that drugs identify to strategy screening a describes which apaper Cor’s published lab addition, In homeostasis. restriction mimetic properties. mimetic restriction drugs reduce that C/EBP (2017). C.F. discovery of the for Ascreening strategy Calkhoven, O., Pless, G., Kortman, J., T., Reinshagen, Ackermann, Müller, C., M.A., Zaini, 14;8(1):2120. Dec 2017 Commun. lignano. Macrostomum model “Nat flatworm transgenesis regenerative the and of sequence genome annotated (2017). E. Efficient P&Berezikov Ladurner L, Schärer A, Aboobaker V, Guryev S, D, Mouton Olivieri PM, W,Qi Weissert DB, Vizoso T, J, Wunderer Demircan L, F, Glazenburg Beltman M, Grudniewska M, Grelling K, Mulder de K, D, Ustyantsev Simanov J, Wudarski C/EBP of switch regulated acetylation and (2017). SIRT1 C.F. Ap300 Calkhoven, V. Guryev, and F., O.H., Krämer, Fusetti, K-H., Gührs, G., Kortman, G., T., Hartleben, T., Ackermann, Jong, de Müller, C., M.A., Zaini, α controls mitochondrial function. ’s group has been successful in annotating the genome of of genome the annotating in successful ’s been has group β - LIP translation calorie potential with LIP Scientific Rep. 7:42603. Rep. Scientific α as a key mediator of energy energy of mediator akey as Cell Reports, accepted. Cell Reports, (published in Nature 15

A Closer Look Michael Chang’s group published a paper in which they determine what the minimal end of a telomere is and how the ends of chromosomes are recognized Awards differently than DNA breaks. In addition, his group collaborated with Peter Lansdorp’s and Victor Guryev to develop a method to employ Strand-Seq in Several of ERIBA’s students or postdocs won awards. Johannes Jung was yeast (published in eLife). awarded the New Investigator Prize at the 46th Annual Meeting of the International Society for Experimental Hematology in Frankfurt. Claussin, C., Porubský, Spierings, D.C.J., Halsema, N., Rentas, S., Guryev, V., Lansdorp, P.M.*, and Chang, M.* Genome-wide mapping of sister Weilin Liu, postdoctoral fellow shared between the labs of Gerald de Haan, chromatid exchange events in single yeast cells using Strand-seq. elife, Peter Lansdorp and Floris Foijer was awarded the Chinese Government Award in press. for Outstanding Students Abroad. This prize was awarded to Weilin for his *Co-corresponding author excellent PhD work in the lab of Hans Jonker at the University Medical Center Groningen that yielded publications in PNAS and Nature.

Marco Demaria’s team identified transcriptome signatures associated with Olga Sin, a former PhD student at Nollen’s group who graduated in 2016, was specific senescent cell types and showed that the senescent phenotype is awarded a prestigious Rubicon grant by NWO. Olga has moved to the Max dynamic, changing at varying intervals after senescence induction. These novel Planck Institute for Molecular Biomedicine, in Germany, where she will transcriptome signatures, published in Current Biology, may help to investigate how defective protein production is linked to neurodegeneration.. discriminate among diverse senescence programs, but also as the basis for developing drugs specifically interfering with sub-types of senescent cells. Georges Janssens, a former PhD student of the Veenhoff group who graduated in 2016, was awarded a FEBS long-term fellowship. After a first postdoc at former Hernandez-Segura A, de Jong TV, Melov S, Guryev V, Campisi J, ERIBA PI Christian Riedel at the Karolinska Institute, he moved to the Demaria M Unmasking Transcriptional Heterogeneity in Senescent Cells. Houtkooper lab at the AMC Amsterdam, where he will continue his career Curr Biol. 2017 Sep 11;27(17):2652-2660.e4. studying modulators of ageing. A Closer Look A Closer

Anita Pras in Ellen Nollen’s lab won this year’s ERIBA Trainee Award. Ellen Nollen’s group, together with Cor Calkhoven and Victor Guryev,

published a paper in Molecular Cell in which they identify a novel, small non- A Closer Look coding RNA-mediated mechanism that is involved in disease-associated protein 16 aggregation. Graduations 17

Sin O, de Jong T, Kudron M , Zaini A , Aprile F.A , Seinstra R, There were six students in ERIBA who successfully defended their PhD thesis, Mata-Cabana A, Stroo E, Willinge Prins R, Martineau C, Wang H.H, and have since moved on to their next position. These include David Porubsky Hogewerf W, Steinhof A, Wanker E.E, Vendruscolo M, Calkhoven C.F, (Lansdorp lab, currently at the Max Planck Institute for Informatics, Saarbrüken), Reinke V, Guryev V, Nollen E.A.A. Identification of an RNA Pol III- Magda Grudniewska-Lawton (Berezikov lab, now at Rutgers University, New associated regulator of small non-coding RNAs that is linked with Jersey), Mohammad Amr Zaini (Calkhoven lab, now at VUmc, Amsterdam), disease-associated protein aggregation. Mol Cell. 2017 Mar 16;65(6):1096- Clémence Claussin (Chang lab, now at Sloan Kettering Institute, New York), 1108.e6. Hilda van den Bos (Lansdorp lab, now a Postdoctoral Fellow in ERIBA) and Helen Michels (Nollen lab, now in Polycheck in Germany).

Liesbeth Veenhoff wrote a book chapter on how to use a combination of compu­tational methods and in vivo measurements of transport kinetics in wild type, mutant and aged nuclear pore complexes to understand how the NPCs are Scientific Dissemination selective gates. and Public Outreach

For the second time, ERIBA organised the Molecular Biology of Ageing Meeting Grants in Groningen, and once more we succeed to gather world-leading scientists working in the diverse research areas that are relevant for understanding the ERIBA scientists secured external funding, totalling 3,1 M Euro. These grants biology of ageing and more than 200 participants attended this event included a VIDI and Aspasia award to Judith Paridaen, from the ‘Nederlandse (www.bioageing.nl). The third edition will happen in the Fall of 2019. Organisatie voor Wetenschappelijk Onderzoek’, three grants from the Dutch Cancer Society to Cor Calkhoven and Marco Demaria, and a grant from the ERIBA’s scientists were also involved in numerous outreach activities in which Landsteiner Foundation for Blood Transfusion Research to Gerald de Haan. they aim to share their findings with society at large. In 2017 we hosted many Detailed information can be found in page 26. visitors to our labs and participated in local Science Fairs. See pages 38 and 39 of this report for more information on outreach and dissemination activities. 18 Figures and Facts

Facts and Figures and Facts 19

Facts and Figures 20 Figures and Facts

Scientific Publications Publications Scientific 3. 2.  1. Berezikov Eugene Leader: Group Mechanisms of Regeneration and Regulation Cell Stem of Laboratory 2017 IN PUBLICATIONS SCIENTIFIC OF NUMBER Oct 30;8(11). E298. pii: Oct Macrostomida).(Platyhelminthes, g li Macrostomum of Evolution Karyotype Evidence Rearran ofFirst Intrachromosomal Chromosome Flatworms: Evolution in the Free-Living E Berezikov N, Ershov KS, Zadesenets 8;9(415). Nov eaam8574. 2017 pii: Med. Transl Sci OPLAH. of effects protective the and tion Accumulation ofAccumulation 5-oxoproline in myocardial dys P. Meer der van R, Bischoff P,Harst RA, Boer de E Berezikov WH, Gilst van DJ, Veldhuisen van Voors AA, JM, Deursen van B, Sluis de van IJ, Domian ES Ovchinnikova HHW, Tromp Silljé J, A, Gil Pol A, der van li re the of trans Efficient P, Ladurner E Berezikov L, Schärer A, Aboobaker V, Guryev S, D, Mouton Olivieri PM, Weissert DB, Glazenburg L F, Beltman M, Grudniewska M, Grelling Wudarski J g Nat Commun. 2017 Dec 14;8(1):2120. Dec 2017 Commun. Nat nano. g enerative flatworm model Macrostomum Macrostomum model flatworm enerative , Simanov D, Ustyantsev K, de Mulder K, K, Mulder de K, D, Ustyantsev , Simanov g , Demircan T, Wunderer J, Qi W, Qi T, J, Vizoso Wunderer , Demircan enesis and g annotated , Vreeswijk-Baudoin I, Hoes M, M, Hoes I, , Vreeswijk-Baudoin Publications per Research Group Genes (Basel). 2017 2017 (Basel). Genes enome sequence , Rubtsov NB. NB. , Rubtsov nano nano g ements in in ements , van der der , van ­func . ­ 4. Vegter EL, EL, Vegter 6.  5. Vegter EL, EL, Vegter 7. reg the in expression gene P. specific Ladurner Organ E Berezikov C, Beisel A, Aboobaker D, Kao G, Carta R, Pjeta J, Wunderer B, Lengerer Nucleic Acids Res. 2017 Jun 2;45(10):6253. 2;45(10):6253. Jun 2017 Res. Acids Nucleic localize to heterochromatin. structures quadruplex PM Lansdorp BNG, Giepmans OCM, Sibon E Berezikov H, AV, Lipps J, Romashchenko Postberg K, Nishida AHG, Wolters J, RD, Kuipers Kalicharan NA, RF Hoffmann S0012-1606(17)30283-X. pii: 28. Jul 2017 Jaarsma T, E Berezikov Jaarsma May 5;12(5):e0177242. failure. signature in heart microRNA circulating human the reflect not do models failure P. Meer der heart van Rodent RA, Boer de Voors AA, E Berezikov Velde AR, der van Pol A, der van LMG, 2017 Aug;106(8):598-609. 2017 Aug;106(8):598-609. rehospitalizations. vascular-related disease and cardio atherosclerotic with associated circulatin eneratin microRNA levels in heart failure patients are patients failure levelsg microRNA in heart 55 Ovchinnikova ES Ovchinnikova Ovchinnikova ES Ovchinnikova g li Macrostomum of g tail 2017 Mouton S Mouton YM, , Moshkin Low P, Low Meer der , van Voors AA. , van Veldhuisen DJ, DJ, Veldhuisen , van HHW, Meems , Silljé Clin Res Cardiol. Cardiol. Res Clin PLoS One. 2017 2017 One. PLoS , Salvenmoser W, , Salvenmoser nano 2016 ·40 2016 2015 ·39 2014 ·34 2013 ·37 2012 ·22 2011 ·12 , Grzeschik , Grzeschik , Dev Biol. Biol. , Dev Guanine . Guanine

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, ,  3.  1. Calkhoven Cor Leader: Group and Age-Related Diseases Ageing In Regulation Gene of Laboratory  3.  2.  1. Chang Michael Leader: Group Integrity Telomeres Genome of and Laboratory 2.  4. e23783. e23783. telomeres. short critically from breaks double-strand DNA separates threshold M Chang RK, J Strecker Zaini, M.A. Zaini, C/EBP of switch acetylation SIRT1 and regulated A p300 V. Guryev, O.H., Krämer, F., Fusetti, K-H., Gührs, G., Kortman, G., Hartleben, Sin O Sin December 19, accepted. function. and Treg effector differentiation Tcell biosynthesis, protein control to V. Roquin PI3K-mTORHeissmeyer suppresses si Mand D, Zavolan Baumjohann A, Krug J, Huehn effect? reg M Chang K, Paeschke S, Stinus author Dec.12 2017;6:e30560. *Co-corresponding inevents sin mapping of sister chromatid exchan Genome-wide V Guryev S, Rentas N Halsema DCJ, D, Spierings Porubský C, Claussin mimetic properties. restriction with potential translation calorie LIP Hrab S, Marschall A, Maiser J, Klein S, Floess A, Heiseke S, D, Edelmann Alterauge J.C., Guimaraes K, D,Hu Essig accepted Seinstra R Seinstra Martineau C Martineau R, strategy for the discovery of dru of discovery the for strategy Kortman G T Ackermann C, Müller MA, Zaini 16;65(6):1096-1108.e6. Mar 2017 Cell. Mol a protein disease-associated with is linked associated regulator of smallIII non-codin V Guryev C Calkhoven M, Vendruscolo E.E, Wanker ulation by the Pif1 helicase: alen helicase: Pif1 the by ulation ĕ , de Jong T, Kudron M, Zaini A T, M, Jong , de Kudron α Calkhoven C.F Calkhoven H, Leonhardt M, Angelis, de Curr Genet. 2017 Oct 20. 20. Oct 2017 Genet. Curr controls function. mitochondrial † Co-first author,Co-first *Co-corresponding author Identification of an RNA Pol RNA an of Identification E.A.A. , Nollen † Mata-Cabana A , Mata-Cabana Stinus S , Stinus (2017). CF O, Calkhoven , Pless A screenin g , Müller, C., de Jong, T., Ackermann, T. Jong, de , Müller, C., le yeast cells usin cells yeast le A sharp Pif1-dependent D.**, Durocher A sharp Pif1-dependent Hogewerf W Hogewerf , Wang H.H, Lansdorp PM, Lansdorp Sci Rep. 2017 Feb 15;7:42603. 15;7:42603. Feb 2017 Rep. Sci † Pliego Caballero M Caballero , Pliego Calkhoven, C.F. (2017). C.F. Calkhoven, and eLife. 2017 Aug 3;6. pii: pii: 3;6. Aug 2017 eLife. Immunity. 47, 1067–1082 47, Immunity. 1067–1082 E, Willinge Prins E, , Stroo g Strand-seq. g s that reduce C/EBP reduce s that . Telomerase g Chang M Chang *, th-dependent th-dependent , Aprile F.A, F.A, , Aprile , Reinshagen J, J, , Reinshagen Cell Reports, Reports, Cell gg RNAs that that g RNAs , Steinhof A, A, , Steinhof .F, V, Reinke eLife eLife reg , Szilard , Szilard g ation. *. *. nalin g , e ,

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g g - ,  5. 4. 1. Tatché Colomé Maria Leader: Group Epigenetics Quantitative of Laboratory  6.  1. Haan de Gerald Leader: Group Cells Stem and Biology Ageing of Laboratory P, Ferronika 3. 2. dama to DNA is not by accompanied sensitivity instability M Chang LM, Veenhoff IL, Rempel GE, Janssens D, SN, Mavrova Novarina 19;7(1):5862 Jul 2017 Rep. Sci Internalization intoFluorescent Nanodiamond Cells. Transformation Applicable Generally Protocols for Novarina D Novarina FP, S, D, Roig Hommelet Perona-Martinez E, Ellermann MV, Koot SR, Hinterding KJ, Laan der van SR, Hemelaar Magliarelli HF,Magliarelli Taudt A MP, F, G, D, Baltissen Richter Gómez Meszaros S, Gras Le LZ, Shahidian A, AF,Kebede Nieborak 13;4(5):169-174. Apr Saccharomyces in cerevisiae changes protein abundance andage-dependent localization M Chang and LM, Veenhoff IL, D, Rempel Novarina M, Cabrera Jun;54:1-7. (Amst). 2017 Nov 28. pii: jem.20171904. jem.20171904. pii: 28. Nov 2017 Med. JExp engraftment. cell stem to Directions G Haan de L, Bystrykh ME, Belderbos 1;28(7):1668-1670. Jul 2017 Oncol. Ann lun asmall-cell in metastasis distant and polyclonal seedin revealed mono- assessed at sin the alterations number PM Lansdorp HJM, Groen W, F Foijer Timens AJ, Wekken Porubsky D K, Kok TJN, Hiltermann A, Saber Dec;20(12):1576-159056 2017 Lett. Ecol forward. way the and species, Evidence from model and non-model epigenetics: plant KJF. Verhoeven Ecological K, PF, Ullrich Trucchi E, Stadler SA, Rensing SJ, O, Prohaska Paun L, Opgenoorth V, M, Mirouze Latzel C, Lampei I, Kronholm TP, Gurp K, van Heer I, Grosse A, Gogol-Döring Colomé-Tatché M E, O, Bucher Bossdorf C, Becker C, Alonso CL, Richards chromatin. active of amark is propionylation Histone R. Schneider Tatché M g in g a , Ricci R, Daujat S, Vermeulen M, Mittler G, G, Mittler M, Vermeulen S, Daujat R, , Ricci Nat Struct Mol Biol. 2017 Dec;24(12):1048-10 Dec;24(12):1048-10 2017 Biol. Mol Struct Nat g van den Bos H, Taudt A, Spierings DCJ Taudt Spierings H, Bos A, den van Chang M Chang H, , Takahashi ents in a in ents A simple microfluidic platform to study study to platform microfluidic . Asimple , Durka W, Engelhardt J, Gaspar B, B, Gaspar J, W,, Durka Engelhardt g ed yeast cells. yeast ed , Margueron R, Colomé- R, , Margueron Increased g . Increased Copy Copy A. Berg den , van , Colomé-Tatché M . Microb Cell. 2017 2017 Cell. . Microb cancer patient. g cancer DNA Repair Repair DNA , and Schirhagl R. R. Schirhagl , and patterns of of g patterns g enome enome le-cell level le-cell Left or right? right? or , Left , van der der , van

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Facts and Figures 22 Figures and Facts

 3. 2. 1. Group Leader: Marco Demaria pathologies age-related and senescence Cellular of Laboratory 6.  4. 5.  4. 3.  2. Interventions for a Interventions M Demaria A, Soto-Gamez environment. g and a creates pro-re osteoarthritis traumatic post- of development the prevents cells senescent of Clearance JH. Elisseeff J, Campisi JM, Van Deursen DJ, Y, Poon Baker JW, N, Chung DH, David Kim A, Vasserot M Demaria RM, Laberge C, Kim Oh, Jeon 11;27(17):2652-2660.e4. hetero M Demaria J, Campisi V TV, Guryev Jong de A, Hernandez-Segura g cells stem G Haan de SC, Buisman JJ,  Jung 15;129(24):3210-3220. Demaria M. Demaria Today. Discov Drug May;22(5):786-795. 2017 revealed by cellular barcodin xeno murine in leukemia human of distribution LVBystrykh Gand Haan de E, Bont de E, Zwart S, Sowdagar ME Belderbos Sep;53:26-30. 2017 function. cell stem hematopoietic affect G Haan de DNA lesions. DNA of requires tolerance oxidative system hematopoietic integ and Genomic functional N. Wind G Haan de LJ, Rasmussen M, Moriya C, Spek der Dingemanse-van K, Hashimoto DCF, Salvatori B, Loon van R, Aprigliano M, Bosshard treatment? S Lazare van Os RP Os van S Lazare S, Chen A, Tsaalbi-Shtylik A, Martín-Pardillos blood-2017-06-746412. cells. stem A S. Lazare Gand Haan De g eneity of senescent cells. of senescent eneity Ausema A , Ausema Blood. 2017 Nov 15. pii: pii: 15. Nov 2017 Blood. , Dethmers-Ausema A Mol Cell Oncol. 2017 Apr 3;4(3):e1299666. 3;4(3):e1299666. Apr 2017 Oncol. Cell Mol Lifelong dietary intervention does not not does intervention dietary . Lifelong Leukemia. 2017 Mar;31(3):529-531. Mar;31(3):529-531. 2017 Leukemia. old? et Blood. 2017 Sep 28;130(13):1523-1534. Sep 2017 Blood. Senescent cells: new cells: tar Senescent Clonal selection and asymmetric asymmetric and selection . Clonal Nat Med. 2017 Jun;23(6):775-781. Jun;23(6):775-781. 2017 Med. Nat , Koster K, Ausema B, Jacobs S, S, Jacobs B, Ausema K, , Koster g in g van Os R Os van G, Dijk van AC, , Reijne senescence. cellular of case : the . Unravellin , Raaijmakers MHGP, de , Raaijmakers g g in Blood. 2017 Jun Jun 2017 . Blood. Therapeutic . Therapeutic of hematopoietic g of hematopoietic Curr Biol. 2017 Sep Sep 2017 Biol. Curr transcriptional g transcriptional Do hematopoietic . Do hematopoietic , Fakouri NB, NB, , Fakouri g rity of the the of rity et for an old old an for et Exp Hematol. Hematol. Exp , Rathod S, S, , Rathod enerative g , rafts rafts , , 7. 6. 5. P, Ferronika 4. 3.  2.  1. Foijer Floris Leader: Group Development and Disease in Instability Genomic of Laboratory 5.

Mar 20;6. pii: e20873. e20873. pii: 20;6. Mar and hepatocellular carcinoma. lymphoma T-cell acute of models mouse in tolerated is gene point Deletion of the MAD the of Deletion PK. RT, PM Lansdorp Bronson B, Furey Takemoto B, D, Hare A, Lutum-Jehle S, Davis SZ, Xie ojr F Foijer 20;19(12):2423-2431. Aneuploidies. Structural Produce Propagation of Chromosome Seg F Foijer PM, Lansdorp DCJ, Spierings B, Bakker JA, Raaijmakers M, Soto Jul;39(7). 2017 Bioessays. 10.1002/bies.201400140). DOI chromosome checkpoint separation F. Foijer SWM, Bruggeman I, Bockaj 1;28(7):1668-1670. Jul 2017 Oncol. Ann lun asmall-cell in metastasis distant and polyclonal seedin revealed mono- assessed at sin the alterations number PM Lansdorp HJM, Groen W, F, Foijer Timens AJ, Colomé-TatchéWekken M Porubsky D K, Kok TJN, Hiltermann A, Saber 17;8:15981. Jul 2017 Commun. Nat cells. cancer recombination-deficient in homologous mitosis promotes PARP cytotoxicity inhibitor-induced through MATM. Progression Vugt van S, Rottenberg P,Bouwman F Foijer AM, Heijink Talens E, PM, F, Gogola C, Schoonen Stok S1357-2725(17)30249-2. pii: 23. Sep in cancer. integrity genomic quantify to sequencing F. Foijer PM, Single-cell Lansdorp DCJ, Spierings B, Bakker H, Bos den van 21. Nov 2017 Bioessays. Concepts,Different Consequences. Different Schukken KM Feb;7(2):165-176. Discov. 2017 Cancer relapse. cancer and chemotherapy to effects adverse promotes senescence Cellular J. Campisi H and Muss NE, D, Sharpless Zhou S, Melov BK, Kennedy A, Bruin Wang de B, A, Valdovinos S, Kilmarx E, Academia S, Alston AM, Deal N, Mitin C, Le F, K, Alimirah Koenig M Demaria Bakker B, Spierings DC Spierings B, Bakker LA, , Albacker van den Bos H, Taudt A, Spierings DCJ Taudt Spierings H, Bos A, den van , O’Leary M, Chang J, Shao L, Liu S, S, Liu L, Shao J, Chang M, , O’Leary Foijer F , Foijer , Tarsounas M, Blatter S, Jonkers J, J, Jonkers S, Blatter , Tarsounas M, , Medema RH. p RH. , Medema , CIN and Aneuploidy: Aneuploidy: and , CIN 2 L 1 spindle assembly check Copy Copy A. Berg den , van Int J Biochem Cell Biol. 2017 2017 Biol. Cell JBiochem Int Cell Rep. 2017 Jun Jun 2017 Rep. Cell reg cancer patient. g cancer , Bradley A, Sorger Sorger A, , Bradley (retrospective on on (retrospective ation Errors that Revisiting the patterns of of g patterns g le-cell level le-cell 53 Elife. 2017 2017 Elife. Prohibits Prohibits

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, , 3. 7.  6.  5.  4. 1. Guryev Victor Leader: Group Ageing Structure Genome of Laboratory 9. 2. 8.  lipase Cg lipase ES. Peptide phospho microarray profiling identifies V Guryev M, Scherr M, Eder C, Schoenherr HJ, Lourens TM, Boer de FJG, Scherpen H, Mahmud III-associated reg III-associated V Guryev C.F Calkhoven M, Vendruscolo E.E, Wanker W Hogewerf Wang H.H, C, Martineau R, R Seinstra O Sin Jul;38(7):749. highly admixed population. V Guryev motifs in transcribed g transcribed in motifs suppresses recombinationhelicase at G-quadruplex DCJ Spierings Van N Wietmarschen 11;27(17):2652-2660.e4. Hetero V Hernandez-Segura A 67354. t(8;21) AML. events inevents sin mappin Genome-wide M V, Chang PM, Guryev S, Lansdorp Rentas N Halsema DCJ, D, Spierings Porubsk C, Claussin InTechInstability’, 2017. 30, Aug. of Genomic – Manifestation AAbnormalities Hallmark de PM. F, Foijer DCJ, Lansdorp Spierings H, Van Bos den 6;40(3):313-322.e5 g haplotypin whole-chromosome V D Porubsky 2017;6:e30560. Dec.12 Tumori to Promote Spontaneous Is Sufficient Amplification D, F Foijer Lambrechts PM Lansdorp DC, Spierings B, Vitre J, Lu J, Moyett B, Boeckx B, Bakker MS, Levine enomes. Demaria M Demaria J, , Campisi Lansdorp PM, Lansdorp g enerative disease? enerative Does aneuploidy in the brain play a role in neuro in arole play brain the in aneuploidy Does de Jong T Jong , de g g eneity in Senescent Cells. in Senescent eneity enesis in Mammals. amma 1(PLC- amma Nat Commun. 2017 Nov 3;8(1):1293. Nov 2017 Commun. Nat Assessment of variant patho of variant . Assessment Identification of an RNA Pol RNA an of Identification E.A.A. , Nollen Mata-Cabana A , Mata-Cabana Oncotarget. 2017 Jun 27;8(40):67344- Jun 2017 Oncotarget. g Guryev Guryev JO, AD, Korbel Sanders S, , Garg le yeast cells usin cells yeast le Guryev V , Guryev ulator of non-codin small , Kudron M, Zaini A M, , Kudron Dense and accurate accurate T. and Dense , Marschall Book chapter in chapter Book ‘Chromosomal enes. g of sister chromatid exchan γ , Holland AJ. Centrosome AJ. , Holland de Jong TV Jong , de Merzouk S , Merzouk 1) as a potential tar 1) apotential as . Unmaskin Lansdorp PM, Lansdorp Hum Mutat. 2017 2017 Mutat. Hum bioRxiv 2017 August 7 3252. 73252. August 2017 bioRxiv Dev Cell. 2017 Feb Feb 2017 Cell. Dev Stroo E , Stroo , Cleveland DW,, Cleveland g Strand-seq of individual g of individual Curr Biol. 2017 Sep Sep 2017 Biol. Curr Guryev Guryev S, , Melov g Transcriptional Halsema N , Halsema , Aprile F.A, F.A, , Aprile , Willinge Prins g enicity in a in enicity , Steinhof A, A, , Steinhof RNAs that that g RNAs BLM . BLM g , eLife , eLife et for for et , De Bont Bont , De , Reinke V,, Reinke . , ­ g e ­ ,  5.  4. 3.  2. 1. Lansdorp Peter Leader: Group Ageing and Instability Genetic of Laboratory 8. g of individual haplotyping whole-chromosome V Porubsky D revisionUnder at Communications. Nature g transcribed in motifs suppresses recombinationhelicase at G-quadruplex DCJ Spierings Van N Wietmarschen reviewUnder at Nature. invariation human g structural haplotype-resolved of discovery platform Multi- C. Lee EE, Eichler J, T, Korbel Marschall RE, Mills Talkowski S, M, Ye Devine A, K, Bashir X, Shi J, Sebat Kwok PY, MB, PM Lansdorp Gerstein K, P, Flicek B, Ren Chen SK, Lam L, Ding G, Jun X, Bradley Zheng- Q, Xu Zhu W, M, C, Xiao Zhang Welch AME, Ward A, DCJ, Spierings A, Stütz M, Ryan G, Rosanio Y, Qiu A, Pang S, Panagiotopoulou Kyriazopoulou A, Noor C, Nodzak F, BJ, Navarro Nelson KM, Munson WP,Lee S, SP, Lee P, KV, Meiers Marks Martinez J, Lee Kwon S, JY, JE, Kumar Lee J, Korlach W, CL, Koh V, Haynes-Heaton Guryev M, D, T, Gujra Galeev Gorkin J, Flores A, Farrell L, Clarke DM, NT, Church Chuang X, Chong CS, Chin X, Chen C, Chen E, Cerveira H, Cao S, P, Cantsilieris D, Audano H, Antaki Brand A, Hastie AM, F, D, Wenger Lee Hormozdiari X, Kong ZN, Kronenberg S, Fairley RE, Handsaker Wen J, X, Fan RL, Collins L, O, Guo Rodriguez EE, T, D, Gardner Rausch Porubsky A, Malhotra MJP, X, AD, Zhao Chaisson Sanders October 2017 23 Accepted 1:2467-2472. 2017 Advances Blood AML. PMLansdorp V Guryev yeast cells using Strand-seq using cells yeast exchangemapping of chromatid in sister events single author. MCo-corresponding Genome-wide Chang D Porubsk 2017. 474:213-216. Biophys. Biochem Dokl Yakut of exomes. analysis specific Population VL. Osakovsky ML, Filipenko YS, Aulchenko EA, Sokolova UA, Boyarskih TM, Tsepilov YA, Sivtseva VP Guryev SS, Sharapov AS, Zlobin 16;65(6):1096-1108.e6. Mar 2017 Cell. Mol a protein disease-associated with is linked enomes. Lansdorp PM, Lansdorp Nat Commun. 2017 Nov 3;8(1):1293. Nov 2017 Commun. Nat Lansdorp PM, Lansdorp Spierings DCJ , Spierings Guryev Guryev JO, AD, Korbel Sanders S, , Garg , Maintenance of telomere length in in length telomere of , Maintenance Guryev V , Guryev Dense and accurate accurate T. and Dense , Marschall enomes. enes. Merzouk S , Merzouk , Clémence Claussin Lansdorp PM, Lansdorp , eLife Dec.12 2017;6:e30560 2017;6:e30560 Dec.12 , eLife Halsema N , Halsema bioRxiv 2017 August 7 3252. 73252. August 2017 bioRxiv bioRxiv 2017 Sept 193144. 193144. Sept 2017 bioRxiv Bevova MR , Bevova Halsema N , Halsema , Rentas S, S, , Rentas , Marth G, G, , Marth gg BLM . BLM reg ation. , , ,

23

Facts and Figures 24 Figures and Facts

Levine MS, MS, Levine 15. 14. 13. 12. 11. 10. ernk P, Ferronika 9. 8. 7. 6.    2017 Mar 20;6. pii: e20873. e20873. pii: 20;6. Mar 2017 T-cell and hepatocellular carcinoma. lymphoma g checkpoint assembly spindle MAD2L1 the of Deletion PK. RT, PM Lansdorp Bronson B, Furey Takemoto B, D, Hare A, Lutum-Jehle S, Davis SZ, Xie 2;45(10):5913-5919. Jun 2017 Res. Acids DNA. stranded single thymidine-rich restrained 1 antibody monoclonal quadruplex Lambrechts D, F Foijer Lambrechts DC Spierings Foijer F Foijer Kazemier HG 2;45(10):6252. Jun 2017 Res. Acids Nucleic cells. mammalian in DNA G-quadruplex of Detection Jr, D, PM RM Lansdorp Sen Brosh FB, Johnson J, Platt Wu Y, EA, YC, Chavez A, Huang Henderson homologs. individual of characterization the enables Strand-seq by PMLansdorp DCJ Spierings M, Hills E, AD, Falconer Sanders 20;19(12):2423-2431. Aneuploidies. Structural Produce Propa PMLansdorp Bakker B Bakker JA, Raaijmakers M, Soto 1;28(7):1668-1670. Jul 2017 Oncol. Ann lun asmall-cell in metastasis distant and polyclonal seedin revealed mono- assessed at sin the alterations number PM Lansdorp HJM, Groen W, F Foijer Timens AJ, Wekken Porubsky D K, Kok TJN, Hiltermann A, Saber contiBAIT. PMLansdorp A, Karsan M, Borkowski M, Gottlieb M, Hills K, O’Neill S1357-2725(17)30249-2. pii: 23. Sep g PM H Bos den van Oct;140(4):1120-1129.e1. 2017 J hypoplasia. cartilage-hair with patients in phenotype immune cellular to contribute homeostasis telomere lymphocyte in Defects PM Lansdorp KA, Strauss G, Aubert enomic integrity in cancer. integrity enomic , Foijer F. sequencin , Foijer Single-cell g ation of Chromosome Seg Bakker B Bakker LA, , Albacker Bioinformatics. 2017 Sep 1;33(17):2737-2739. Sep 2017 Bioinformatics. Nat Protoc. 2017 Jun;12(6):1151-1176. Protoc. Nat Bakker B Bakker van den Bos H Bos den van ene is tolerated in mouse models of acute acute of models mouse in tolerated is ene Lansdorp PM, Lansdorp Paeschke K , Paeschke Foijer F , Foijer Single-cell template sequencing. Single-cell strand Assembling draft genomes using genomes draft . Assembling Bakker B , Bakker , Boeckx B, Moyett J, Lu J, Vitre B, B, Vitre J, Lu J, Moyett B, , Boeckx , Holland AJ. Centrosome AJ. , Holland , Medema RH. p RH. , Medema Spierings DCJ , Spierings , Taudt A Copy Copy A. Berg den , van Int J Biochem Cell Biol. 2017 2017 Biol. Cell JBiochem Int Lansdorp PM, Lansdorp , Cleveland DW,, Cleveland Allergy Clin Immunol. Immunol. Clin Allergy , Colomé-Tatché M Spierings DC , Spierings Cell Rep. 2017 Jun Jun 2017 Rep. Cell regation Errors that regation to quantify quantify g to Spierings DCJ , Spierings H cancer patient. g cancer , Bradley A, Sorger Sorger A, , Bradley cross-reacts with with 6 cross-reacts , Rider NL. NL. , Rider Spierings DCJ , Spierings patterns of of g patterns g le-cell level le-cell 53 Prohibits Prohibits Lansdorp , Lansdorp Guanine . Guanine , van der der , van . Elife. Elife. , , Yue Y, Nucleic ,

, ,  5. 1. EllenGroup Nollen Leader: Ageing of Neurobiology Molecular of Laboratory 4.  3.  2.  16. A natural product inhibits the initiation of the inhibits product A natural CM. Dobson EA F, Chiti C, Nollen Cecchi N, Cremades FA, GT, Aprile P, Sormanni Heller R, SW, Chen Limboker R, Cascella P, Flagmeier SI, Cohen JB, Kirkegaard PK, Challa MB, M Perni EAA A Mata-Cabana P, CB, Kukic Andersen MA, Yoshimura Y, Holmberg Instability’, InTech Aug.30, 2017. of Genomic – Manifestation AAbnormalities Hallmark disease? degenerative PM sequencin disease candidate g disease candidate prioritization of Parkinson’s and functional Discovery EA Nollen DC, David AB, Singleton A, Brice HR, Morris (IPGDC), Consortium Parkinson’s International CM; Duijn DiseaseGenetics Y, Li Yogi AK, P, Chouhan C, van N, Amin Blauwendraat P, Rizzu M, Castillo-Lizardo J, Simon-Sanchez J, Vandrovcova JA, Botia M, Ryten MA, Nalls JR, Gibbs RI Seinstra H Michels MC, Lechler S, Ye Heetveld IE, H, Jansen A A Cabana Stroo E Stroo 16;65(6):1096-1108.e6. Mar 2017 Cell. Mol a protein disease-associated with is linked III-associated reg III-associated Guryev V Guryev C.F Calkhoven M, Vendruscolo E.E, Wanker W Hogewerf Wang H.H, C, Martineau R, R Seinstra O Sin 19;292(20):8269-8278. interactions. electrostatic H Van Bos den 6;40(3):313-322.e5. Tumori to Promote Spontaneous Is Sufficient Amplification g α Proc Natl Acad Sci U S A. 2017 Feb 7;114(6):E1009-E1017. 7;114(6):E1009-E1017. Feb 2017 USA. Sci Acad Natl Proc ation by of competin -synuclein -synuclein a -synuclein g in , Knowles TP, Vendruscolo M, Bax A, Zasloff M, M, Zasloff A, TP, Bax M, , Knowles Vendruscolo Does aneuploidy in the brain play a role in neuro in arole play brain the in aneuploidy . Does g and Disease. , Mulder FAA. MOAG- FAA. , Mulder de Jong T Jong , de g , Koopman M enesis in Mammals. , Galvagnion C, Maltsev A, Meisl G, Müller Müller G, Meisl A, Maltsev C, , Galvagnion g Nollen E.A.A , Nollen . Cellular Reg Mata-Cabana A , Mata-Cabana Genome Biol. 2017 Jan 30;18(1):22. 30;18(1):22. Jan 2017 Biol. . Genome , Lubbe SJ, Drouet V, Lesage S, Majounie E, E, V, Majounie S, Drouet Lesage SJ, , Lubbe gg reg Spierings DCJ , Spierings ulator of non-codin small , Kudron M, Zaini A M, , Kudron Nollen Nollen SF, M, , Falsone Vendruscolo Front Neurosci. 2017 Feb 14;11:64. 14;11:64. Feb 2017 Neurosci. Front ation and suppresses toxicity. its enes from lar from enes Book chapter in chapter Book ‘Chromosomal , Jain S, Shulman JM, Heutink P. Heutink JM, Shulman S, , Jain and Mata- and E.A.A. , Nollen ulation of Amyloid Formation in in Formation Amyloid of ulation J Biol Chem. 2017 May May 2017 Chem. JBiol Identification of an RNA Pol RNA an of . Identification promotes the a the 4 promotes Dev Cell. 2017 Feb Feb 2017 Cell. Dev Stroo E , Stroo Foijer F , Foijer g with self-protective self-protective g with e-scale whole exome exome whole e-scale , Aprile F.A, F.A, , Aprile , Willinge Prins Lansdorp , Lansdorp , Steinhof A, A, , Steinhof gg RNAs that that g RNAs reg , Reinke V,, Reinke gg ation. re ­

,

­  2. Ghavami A, A, Ghavami 1. Veenhoff Liesbeth Leader: Group Cellular of Biochemistry Laboratory 3. 6.  5. K, Wanzek 4.  3.  2.  1. Paeschke Katrin Leader: Group Repair and Structures Acids Nucleic of Laboratory Veenhoff LM D Novarina Transport Nuclear-Cytoplasmic in NPC. the of domain unfolded of the natively- dynamics molecular Coarse-grained P.R. Apr 13;4(5):169-174. changes in Saccharomyces cerevisiae. protein abundance andage-dependent localization M Chang and M Cabrera Jun;54:1-7. (Amst). 2017 Repair DNA cells. yeast aged in agents damaging DNA to sensitivity by accompanied not is Translation. Promotes and Sequences Coding Target mRNA in Elements G-Rich Binds Protein Acid-Binding Nucleic Juranek SA Sun3 HW, Kazemier H.G. S, Ghosal CH, Danan Gupta, K. D, Sanjay Benhalevy 2;45(10):5913-5919. Jun 2017 Res. Acids DNA. stranded single thymidine-rich restrained 1 antibody monoclonal quadruplex Kazemier HG 27;45(13):7796-7806 Jul 2017 Res. Acids and replication stability. genome and influences regions in Saccharomycesbinds cerevisiae to G-rich 15;45(5):1173-1182. Oct 2017 Trans. Soc Biochem vivo. in function their and helicases Sauer M effect? byregulation the Pif Stinus S Stinus 2. Nov 2017 structures. DNA G-quadruplex regulating E Schwindt Curr Genet. 2017 Oct 20. 20. Oct 2017 Genet. Curr Paeschke K , Paeschke Paeschke K , Paeschke ; NAMB, Springer (2017) Springer ; NAMB, Schwindt E Schwindt Cell Rep. 2017 Mar 21;18(12):2979-2990. Mar 2017 Rep. Cell Novarina D , Novarina Veenhoff LM Mavrova SN , Mavrova Paeschke K , Paeschke The Human CCHC-type Zinc Finger Finger Zinc CCHC-type Human . The A simple microfluidic platform to study study to platform microfluidic . Asimple , Paeschke K , Paeschke Chang M Chang 1 helicase: a length-dependent Chang M , Chang G-quadruplex unwinding . G-quadruplex Paeschke K Paeschke JA, , Capra Rempel IL , Rempel . . Mms Paeschke K , Paeschke , van der Giessen E and Onck Onck Eand Giessen der , van Increased genome instability instability genome Increased , Janssens GE Lansdorp PM, Lansdorp is an assistant for for assistant an 1 is . Telomerase H cross-reacts with with 6 cross-reacts Microb Cell. 2017 2017 Cell. Microb , Veenhoff LM , Hafner M, M, , Hafner Curr Genet. Genet. Curr Rempel IL , Rempel Guanine . Guanine . Mms Nucleic Nucleic 1 , , 25

Facts and Figures Funding/Grants

Funding (Awarded Grants) 2017 Research proposals awarded in 2017

2011/2012 · € 19,2M Principal Role Grant Title Budget 2013 · € 1,41M Investigator 3,1M 2014 · € 0,64M € 2015 · € 1,83M 2016 · € 4,5M Applicant VIDI / NWO The individuality of stem cells € 800.000 Judith Paridaen Applicant Aspasia / NWO --- € 100.000

Klaske Een muismodel om aneuploïdie en missegregatie Applicant de Cock € 4.000 Schukken in vivo te visualiseren Facts and Figures and Facts Anita De endogene functie van de amyloid regulerende Applicant de Cock € 4.000 Pras factor SERF2 in embryonale ontwikkeling

Het identificeren van genen en bijbehorende Mandy Facts and Figures Applicant de Cock genetische netwerken die toxiciteit van TARDP-43 € 4.000 Koopman (TDP-43) moduleren 26 27

Floris The effect of age on iPSc reprogramming Applicant KACST € 132.000 Foijer efficiency and differentiation potential

Modulation of the TSC-mTORC1-mitochondrial Cor Applicant KWF pathway for suppression of MYC-driven € 647.459 Calkhoven tumourgenesis

Characterization of UV-induced senescent cells Applicant KWF € 615.475 during melanoma progression Marco Demaria Senescence Early after Chemotherapy Co-applicant KWF for testicular cancer treatment: Time to act € 373.066 (SAE-CAT) Dissecting the role of Neogenin; a novel receptor Gerald Applicant LSBR required for hematopoietic stem cell proliferation € 438.254 de Haan and engraftment

NOW – Netherlands Organisation for Scientific Research de Cock – Jan Kornelis de Cock Stichting KACST – King Abdulaziz City for Science and Technology KWF – Dutch Cancer Society LSBR – Landsteiner Foundation for Blood Transfusion Research 28 Figures and Facts

in the premises of ERIBA and the University Medical Center Groningen. Center Medical University the and ERIBA of premises the in lectures and talks give to invited been have scientists 2017, prominent many During Invited Speakers Speakers Hetz Claudio Kisker Caroline Vendruscolo Michele Tuckermann Jan Ulrich Helle Ewald Y Collin Korswagen Rik Durocher Daniel Poli Valeria Biffo Stefano Dillin Andrew Host Floris Foijer Floris en Laman Jon Paschke Katrin Nollen Ellen Calkhoven Cor Paescke Katrin Demari Marco Berezikov Eugene Chang Michael Demaria Marco Calkhoven Cor Meeting Ageing

Title of Talk/Lecture of Title neurodegenerative diseases neurodegenerative Proteostasis imbalance and maintenance genome in RecQ4 and XPD helicases two the of role The disease in Alzheimer’saggregation Abeta against molecules small Systematic development of integrity and novel in regulators bone inaction Osteoimmunology receptor Glucocorticoid during replication damage DNA with Dealing for healthy aging healthy for essential is homeostasis matrix Prolonged extracellular migration mechanism in neuroblas aguidance as signaling wnt Cell of modulation intrinsic screens CRISPR with damage DNA to response the Charting cancer and autoimmunity cancer STAT3 factor transcription in the of fae many the thousand: hundred one one, no One, metabolism Translational control of Stress (the Mitokine Mitochondrial Protetoxic of communication The University/Institute Health, Boston, USA Public of School Harvard and Chile Santiago, Chile, of University of Medicine, Faculty (BNI), Institute Neuroscience Biomedical Germany Würzburg, University, Maximilians Julius Biomedicine, experimental for Center Virchow Rudolf Cambridge, Cambridge, UK Cambridge, Cambridge, of University Chemistry, of Dept. Germany of Ulm, University endocrinology, ofInstitute Comparative molecular (IMB), Mainz, Germany Mainz, (IMB), Biology of Molecular Institute ETH Zürich, Switzerland Zürich, ETH Hubrecht Institute, Utrecht Institute, Hubrecht Toronto,Canada of Institute,University Research Lunenfeld Samuel University of Turin,University Italy Center,Molecular bio-technology University of Milano, Italy University Cell Biology at Berkeley, USA Berkeley, at Biology Cell of and molecular Department Event Series Medicine Molecular Series Medicine Molecular Series Medicine Molecular Series Medicine Molecular Series Medicine Molecular Series Medicine Molecular Series Medicine Molecular Series Medicine Molecular Series Medicine Molecular Meetings Friday AgeingMeeting of Biology Molecular

Müller Christine Kennedy Brian Bruening Jens Sorrentino Vincenzo Molenaars Marte Pon Liza Logarinho Elsa Jacobs Jacqueline Meinema Cornelis Anne Jeggo Penny Hoeijmakers Jan Baumann Peter Ferreira Godinho Miguel Karlseder Jan Lingner Joachim Speakers

Host Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Title of Talk/Lecture of Title DNA double strand breaks double strand DNA and telomeres at choice way lifespan in mice lifespan and health- extends EBPß-LIP C/ of expression Reduced mTOR the in Pathway Aging and Differences Sex of metabolism in control circuits Neuronal ­toxicity proteo peptide proteo Enhancing mitochondrial Longevity in Translation Protein and Function Mitochondrial The Interplay between budding yeast in control lifespan and DNA mitochondrial between interactions Reciprocal aging during human decline basis of mitoticMolecular Control repair of path DNA during yeast aging pore complex rearrangements nuclear cause circles DNA breaks double strand DNA of face the in Integrity Genomic Maintaining neurodegeneration and aging from you protects yourKeeping intact genome enough make to alot takes it – biogenesis RNA Telomerase ageing and cancer in shortening telomere of autonomous effects Non-cell CYREN inhibitor NHEJ the S/G2 in by choice pathway Repair DNA of Regulation protection intoprovides damage insights Telomeric chromatin analysis stasis reduces amyloid-ß amyloid-ß reduces ­stasis ­ University/Institute The Netherlands CancerThe Netherlands Institute the Biology of Ageing, UMCG Ageing, of Biology the for Institute Research European Aging on Research for Institute Buck The Research Metabolism for Institute Planck Max de Lausanne École Fédérale Polytechnique Amsterdam Academic Medical Center Center Medical Columbia University University Porto eCelular, i3S, Molecular deIBMC-Instituto Biologia Zürich ETH of Sussex University the at Sciences Life of School Molecular Genetics of MCErasmus Department Center Medical University Kansas Institute, Stowers and HHMI (IRCAN Nice in Aging and Cancer on Research for Institute Salk Institute for Studies Biological Lausanne École de Fédérale Polytechnique Event AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular 29

Facts and Figures 30 Figures and Facts

Tessarz Peter Speakers Rubinsztein David Simon Katja Nussenzweig Andre Pasparakis Manolis Cuppen Edwin Brunet Anne Baumgart Mario Eggen Bart Schosserer Markus Hipp S. Mark Cellerino Alessandro Dansen Tobias

Host Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Title of Talk/Lecture of Title cell fates in health and ageing and health in fates cell stem of regulation epigenetic and of metabolic Integration Neurodegeneration and Autophagy Autophagy and immune aging immune and Autophagy Chromosome Fragility Drives Organization Genome inflammation and homeostasis in tissue Necroptosis stem cells during life during cells stem in adult human accumulation mutation Tissue-specific aging andUnderstanding modeling actions pleiotropic antagonistic widespread reveals furzeri Nothobranchius killifish expression in the short-lived of analysis gene Longitudinal associated changes reveals age- microglia cortical human purified Transcriptomic of analysis healthy lifespan base methylations modulate RNA ribosomal Two distinct aggregation diseases aggregation and misfolding protein in impairment Proteostasis in protein thermal stability thermal protein in protein complexes and changes in multiple loss of stoichiometry protein/transcript correlation, aging of reveals reduction of brain analysis Proteomic and Age-Related Disease and Age-Related of Models Longevity elegans C. in Turnover Rates Protein in Changes Proteome-wide University/Institute of Ageing, Cologne of Ageing, Biology for Institute Planck Max Research Medical for Institute Cambridge Oxford University Oxford Center for Cancer Research, NIH Research, Cancer for Center the University of Cologne University the at Genetics for Institute at the UMC Utrecht UMC the at Medicine Center for Molecular Stanford University Stanford at Aging of Biology the Paul F. for Laboratories Glenn Leibniz Institute on AgingLeibniz - Institute FLI Groningen Center Medical University and Life Sciences, Vienna Sciences, Life and Resources of Natural University Biochemistry of Institute Planck Max Scuola Normale Superiore Normale Scuola UMC Utrecht Event AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular Mallucci Giovanna Speakers Fontana Luigi Diffley John Dumanski Jan Lansdorp Peter Glück Sélène Bruno Peter Keizer de Peter Stewart Sheila A. Serrano Manuel Ori Allesandro Bardin Allison Rando Thomas Ewald Collin

Host Meeting Ageing Demaria Marco Paeschke Katrin Foijer Floris Spierings Diana Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing Meeting Ageing

Title of Talk/Lecture of Title Protein Response for treat Manipulating the Unfolded ment ofment neurodegeneration diseases ageing and age-associated modulation of Nutritional How our are genomes copied disease in aging males Alzheimer’s as well as cnacer of risk increased and mortality Y+higher minus 46XY and instability genomic variation Structural senescence promotes cGAS through fragments chromatin cytosolic sensing immune ofInnate induction senescence of characterization genetic Functional Aging and Chemotoxicity to Response in Homeostasis Tissue Restores Cells scent Sene of Targeted Apoptosis drive tumorigenesis tumor microenvironment the in changes Age-related and reprogramming sene cellular Integrating proteome crypt intestinal the affect diet and Age aging during cell stem adult of alteration genome of Modes rejuvenation and aging cell stem of Mechanism Epigenetics synthesis protein reduced from extension lifespan ditis elegans ATF-5 mediates Caenor of translation Preferential scence ­scence ­hab ­ ­ ­ University/Institute Cambridge of University Neurosciences, Clinical of Department Washington University, USA & di Brescia,Italy Università UK Londen, Institute, Crick Francis Sweden Genomics,Uppsala University, and Genetics Medical of Dept. Canada Fox laboratory Terry Institute/ Research European de Lausanne École Fédérale Polytechnique School Medical Harvard Rotterdam MC Erasmus of Genetics, Department Louis of St. University Washington the at Physiology and Biology Cell of Department Barcelona IRB Biomedicine, in Research for Institute (FLI) Institute Lipmann –Fritz Aging on Institute Leibniz Curie Institut at Center Biology and Developmental Genetics Ageing at University Stanford of Biology the for Center Glenn Zurich ETH Event AgeingMeeting of Biology Molecular Series Medicine Molecular Series Medicine Molecular Series Medicine Molecular Series Medicine Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular AgeingMeeting of Biology Molecular

31

Facts and Figures 32 Figures and Facts

INTERNATIONALS (%) 40 STAFF UNDER EMPLOYEES People FEMALE EMPLOYEES (%) (%)

54% 49% 76% 107 2017 2017 2017 2017 2016 ·45% 2015 ·47% 2014 ·48% 2013 ·47% 2016 ·55% 2015 ·56% 2014 ·56% 2013 · 60% 2016 ·61% 2015 ·63% 2014 ·63% 2013 · 69% 2016 ·92 2015 ·89 2014 ·89 2013 ·81

3 2 1 BY ERIBA HOSTED STUDENTS DOCTORAL INTERNS INTERNS

Students who made internships in various labs various in internships made who Students 2017 of course the in thesis their defended have students these 6 of 2017 in (GSMS) Sciences Medical of School Graduate the by introduced was which Scheme, Bursary GSMS the under ERIBA by hosted are students 10 these of (3) (1,2) NATIONALITIES NUMBER OF NUMBER OF 23 2017 44 49 2017 2017 2016 ·26 2015 ·41 2014 ·41 2013 ·17 2016 ·27 2015 ·26 2014 ·22 2013 · 22 2016 ·22 2015 ·17 2014 ·17 2013 ·18

33

Facts and Figures 34 Dissemination and Outreach – Education

Dissemination and Outreach Education 35

Education – Outreach and Dissemination Education

ERIBA scientists are involved in multiple education “Mol. Biol. of Ageing and Age-related disease” “Molecular and Genetic Age Research at ERIBA” activities. The list below is a selection of major PhD level course, 13 students 6 weeks practical research course, 10 ECTS, 18 BSc November - December 2017 biomedical students contributions to teaching. It excludes a large Coordinator: Liesbeth Veenhoff, Marco Demaria June 2017 Education Objectives: To provide PhD-students an overview of the Coordinator: Cor Calkhoven number of individual lectures and undergraduate current state of our knowledge of the molecular Objectives: “Hands-on” research course for biomedical

student internships. mechanisms underlying ageing and to train academic students. Research topics cover a broad range of Education thinking and discussion. This course will be supported by techniques and model systems related to ageing, lifespan 36 ERIBA team leaders that will provide lectures and reading and age-related diseases. Topics may involve (stem) cells, 37 “Model organisms in Ageing Research” “Molecular Biology of Ageing and materials. yeast, worms, mice, and cover the biological processes of 3 ECTS BSc Junior Scientific Master course, 11 students Age related Disease” signal transduction, transcription, translation, post- Coordinator: Floris Foijer 5 ECTS MSc course, 34 biomedical students “BCN N-track”, research master, 8 students translational modification, protein homeostasis, energy Objectives: Expose medical students to basic research. November 2017 1 January - 31 December 2017 metabolism, chromosome biology, genetics and epi­ Students receive lectures from (junior) scientists on how Coordinator: Liesbeth Veenhoff Coordinator: Liesbeth Veenhoff genetics. Students should choose a first choice lab and they use their model organisms of choice in their ageing- Objectives: In this course we focus on the molecular and Objectives: I act as the coordinator of this track specialized a second choice lab. related research and discuss relevant papers. Furthermore, cellular mechanisms by which tissue and organ function in molecular mechanisms of brain pathologies. students spend some time in the lab, altogether giving deteriorate and homeostasis fails, resulting in ageing and “Specialization Track on the Biology of Ageing” them an impression of the ‘life of a basic biologist’. age related disease. We present the model systems and “Protein chemistry and proteomics methods” and Master students in Biomedical Sciences (FWN), experimental strategies that are used in ageing research. “Model Organisms” master level course, top class II, 20 students “Current Themes in Healthy Ageing” This course will be supported by a team of specialists in MPDI program, 22 students Coordinator: Ellen Nollen 5 ECTS MSc course, 33 students different fields of ageing that will provide lectures and November 2017 Objectives: Coordination and mentoring of students that Coordinator: 2016-’17: Floris Foijer, reading material. The course will be further supported by Week Coordinators: Liesbeth Veenhoff, Michael Chang want to specialize in aging research. The research track 2017-’18: Marco Demaria/Judith Paridaen materials from an online course “Why do we age? The Objectives: Students acquire theoretical knowledge and includes courses that have been developed and are Objectives: How to get most out of scientific seminars. molecular mechanisms of ageing”. The course not only practical experience in a number of techniques, are able to coordinated by ERIBA PIs, which are i) Molecular Biology of Biomedical Science students attend 7- scientific seminars gives an overview of the research field of ageing but also identify an appropriate technique and model system to Aging course and ii) Current themes in Health Ageing. and verbally report on content, scientific excellence and teaches scientific writing, active listening and giving solve a research question, and are able to design an track records of the presenters. Course has been growing feedback to peers. The course unit is compulsory for the appropriate experimental plan for a research question Learning Community Molecular Medicine. rapidly and now has > 30 students/year. ageing track and is an elective in the other tracks of the formulated after critical evaluation of recent articles. January - September 2017, Bachelor program for medicine programs. students. “Genomics data analysis for biologists” Coordinator: Gerald de Haan 1,5 EC GSMS course, 20 PhD students from GSMS In 2014 a new bachelor curriculum for medicine students September 2017 - January 2018: Weekly seminars was implemented, referred to as G2020. Gerald de Haan Coordinators: Victor Guryev, Leonid Bystrykh lead a team that developed the -English taught- curriculum Objectives: Discuss data analysis and educate ERIBA BSc, for ~95 students each year that enroll in the Molecular MSc and PhD students on genome biology tools. Medicine track.

Outreach and Dissemination Outreach and Dissemination ERIBA has been consistently engaged in various February 2, 2017 communication and outreach activities as a mean to Interview for Digital Trends www.digitaltrends.com/cool-tech/chemotherapy-side-effects-eliminated/ effectively bring the general public closer to Staff Members Involved: Marco Demaria research. Through public events, activities for February 8, 2017

schools, tours and many more initiatives, ERIBA Interview for the New Scientist Dissemination and Outreach seeks to connect a wide range of audiences www.newscientist.com/article/mg23331122-300-drug-stops-nasty- 38 chemotherapy-side-effects-in-mice-with-cancer/ 39 outside the academia: public in general, secondary Staff Members Involved: Marco Demaria education students, industry, decision makers, media, and patient organisations. Events

October 14, 2017 Zpannend Zernike (open house at ERIBA) Media Staff Members Involved: Anton Steen, Liesbeth Veenhoff, Judith Paridaen

November 11, 2017 February 2, 2017 Participation in the O&O Show “Food or Fiction” Weekend van de Wetenschap Staff Members Involved: Cor Calkhoven Staff Members Involved: Liesbeth Veenhoff

November 13-27, 2017 Talentenexpositie in de Stad, an initiative of City of Talent Staff Members Involved: Cor Calkhoven

July 28, 2017 Contribution to a Volkskrant article under the title: “Je moet het maar durven: een ongetest middel injecteren” www.volkskrant.nl/wetenschap/je-moet-het-maar-durven-een- ongetest-middel-injecteren~a4508424/ Staff Members Involved: Cor Calkhoven

Interview for City of Talent www.cityoftalent.nl/blog/groningse-muis-leeft-langer-en-blijft-gezonder Staff Members Involved: Cor Calkhoven Erik Gietema Scientific Advisory Board

Scientific Advisory Board Advisory Scientific The Board is comprised of the following distinguished scientists: Scientific Advisory Board

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Jan Hoeijmakers Christine Mummery Johan Auwerx Professor of Molecular Genetics Professor of Developmental Biology Professor and Nestlé Chair in Institute of Genetics Chair of the Department of Anatomy Energy Metabolism Erasmus Medical Center Rotterdam and Embryology Ecole Polytechnique Fédérale in The Netherlands Leiden University Medical Center Lausanne The Netherlands Switzerland

Helle Ulrich Yves Barral Scientific Director of the Institute of Associate Professor of Biochemistry Molecular Biology Department of Biology Professor at the Faculty of Biology ETH Zurich University of Mainz Switzerland Germany Sponsors

The European Institute for the Biology of Ageing is made possible by: Sponsors Ministry of Economic Affairs, Agriculture and Innovation

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The Province of Groningen

Collaboration of the Northern Netherlands (SNN)

The European Union

The Noaber Foundation

The Pediatric Oncology Foundation Groningen (SKOG) European Research Institute for the Biology of Ageing

Visiting address European Research Institute for the Biology of Ageing University Medical Center Groningen Antonius Deusinglaan, 1 Building 3226 9713 AV Groningen The Netherlands

Post address European Research Institute for the Biology of Ageing University Medical Center Groningen Building 3226, Room 03.34 PO Box 196, Internal Zip Code FA50 9700 AD Groningen The Netherlands [email protected] T: +31 (0) 50 361 73 00 www.eriba.umcg.nl