European Research Institute for the Biology of

Annual Report 2019

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Annual Report 2019

2019

ERIBA | Annual Report V2.indd 1 16-07-2020 20:59 Welcome to our Annual Report 2019

Coordination: Gerald de Haan and Megha Upadhyay

Secretarial Support: Sylvia Hoks, Annet Vos-Hassing & Alida de Haan

ژيƺɀǣǕȇƏȇƳXǼǼɖɀɎȸƏɎǣȒȇɀ) Stefan Heinrich

ژيȸǣȇɎǣȇǕ¨ Ridderprint BV | Anand Baldew

Copies: 100

ERIBA | Annual Report V2.indd 2 16-07-2020 20:59 Annual Report Table of contents

1. Foreword by the Director 4

2. Ageing Research at ERIBA 6

3. 2019: Highlights 10

4.Facts and Figures 20

אא ³ƬǣƺȇɎǣˡƬ¨ɖƫǼǣƬƏɎǣȒȇɀٮ

-Funding/Grants 32

-Invited Speakers 35

אג ƺȒȵǼƺ¨ٮ

5.Facilities 46

6.Education 50

7.Outreach & Dissemination 54

זד ³ƬǣƺȇɎǣˡƬƳɮǣɀȒȸɵ ȒƏȸƳِז

9.Sponsors 59

ERIBA | Annual Report V2.indd 3 16-07-2020 20:59 Foreword by the Director 2019 in review

It is a great pleasure to present to you the 2019 Annual Report of the European Research Institute for the Biology of Ageing. This report provides you with an overview of all our activities and achievements, in science, education, business development and outreach. We value all these domains equally, and are proud to share with you all that has been accomplished in 2019.

I write these words in the midst of the Covid-19 pandemic. This pandemic may very well have a major effect on global research and education for quite some time to come. One aspect, highly relevant to what we do in ERIBA, relates to how the virus differentially affects individuals in society. For as yet unclear reasons, globally elderly individuals are far more susceptible to develop critical morbidity compared to young. Thus, like many other diseases such as cancer and dementia, Covid-19 is very much an age-associated disease. Gerald de Haan ³ƬǣƺȇɎǣˡƬ(ǣȸƺƬɎȒȸ In ERIBA we study what ageing is, and why elderly individ- ɖƏǼɀƫƺƬȒȅƺǔȸƏǣǼƏȇƳɀɖɀƬƺȵɎǣƫǼƺɎȒƳǣɀƺƏɀƺِXɎǣɀȒɖȸˡȸȅ believe that only if we understand why cells and tissues in our body gradually cease proper functioning as we age will it be possible to intervene in the ageing process. Therefore, if anything, the Covid-19 pandemic has reinforced our rai- son d’etre and has made us more committed than ever to ƬȒȇɎȸǣƫɖɎƺɎȒˡȇƳǣȇǕȒɖɎɯǝɵɯƺƏǕƺِ

In 2019 we published 61 papers, more than any other year. The large majority of these papers were the result of teams of ERIBA scientists collaborating with each other, or with researchers outside our Institute.

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We believe that collaboration in science, In October 2019 we have organized, for the where multiple teams work towards a third time, the biennial conference series on single goal, is required to reach our purpose: the Molecular Biology of Ageing Meeting the discovery of critical mechanisms of in Groningen. We assembled a stellar team ageing and age-related diseases and the of international speakers to cover many development of new intervention strategies. aspects of the ageing process. One of the keynote speakers was Titia de Lange, who was awarded an honorary doctorate from We remain very committed to contributing our University earlier in the year. Little did ɎȒɎƏǼƺȇɎƳƺɮƺǼȒȵȅƺȇɎǣȇɎǝƺˡƺǼƳȒǔ we know at that time that this was one ȅƏȇɵǝǣǕǝǼɵɎƏǼƺȇɎƺƳ¨ǝ( of the last ageing meeting to be held forח׎׏אƏǕƺǣȇǕِXȇ students joined our training program, and quite some time, as the viral pandemic has similarly, undergraduate students enrolled seriously affected international conferencing. at Universities from all over the world have Excitingly, as I write this foreword, many come to ERIBA. webinars related to ageing have been launched, including a series by Marco ِ ƺȅƏȸǣƏǣȇ0«X) Progress in science is exponential, and it is of ǣȅȅǣȇƺȇɎǣȅȵȒȸɎƏȇƬƺɎȒɀǝƏȸƺȒɖȸˡȇƳǣȇǕɀ with society. In 2019 ERIBA scientists were The upcoming year, 2020, will be an odd involved in many of such outreach activities. year, which all of us will remember vividly. It çȒɖɯǣǼǼˡȇƳƏǼȒȇǕǼǣɀɎȒǔƏǼǼȒɖȸƺǔǔȒȸɎɀǣȇ is uncertain how much longer Covid-19 will this Annual Report. We do not only organize affect the research and education agenda. these outreach activities because they are However, whatever the future will bring, our fun (which they are!), but also to convey the mission and ambition are more viable and .ǣɀƺɀɀƺȇɎǣƏǼ relevant than ever beforeټˡȇƳǣȇǕɎǝǣȇǕɀȒɖɎٻȅƺɀɀƏǕƺɎǝƏɎ to offer future therapeutic opportunities to confront age-associated diseases. We need to understand how proteins properly fold in the brain if it is our aim to target Alzheimer disease. We need to understand why the immune system in elderly functions poorly if it is our aim to ensure that a future Covid-20 pandemic has the same disastrous Gerald de Haan consequences as the -19 pandemic that hit us this year. ³ƬǣƺȇɎǣˡƬ(ǣȸƺƬɎȒȸ May 2020 In 2019 we recruited John LaCava from Rockefeller University in New York City to ERIBA. John is an expert in proteomics and develops sophisticated technology to capture protein complexes from cells to molecularly dissect functional pathways. We very much welcome John and anticipate that his expertise will result in many collaborative projects with scientists in ERIBA and the UMCG.

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ERIBA | Annual Report V2.indd 5 16-07-2020 20:59 Ageing Research at ERIBA

ERIBA is an internationally recognised European research institute located in the city of Groningen, The Netherlands.

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ERIBA | Annual Report V2.indd 6 16-07-2020 20:59 Since its inception in 2009, the institute has grown and established itself as one of ma^e^Z]bg`k^l^Zk\abglmbmnm^lbgma^Û^e] of ageing biology. The institute has state- of-art facilities and focuses on research to understand the causes of ageing.

Research New strategies

Research at ERIBA aims to address ERIBA aims to develop new strategies to phenomena such as genome stability, prevent age-related diseases and increase protein homeostasis decline, metabolic the healthy life span of individuals. The decline, and stem cell loss of function. institute also aims to provide evidence-based These phenomena have been implicated in recommendations for healthy ageing by various age-related diseases such as cancer, discovering new drug targets, specialized neurodegeneration, and diabetes. The disease models, and assays for the purpose research at ERIBA investigates the molecular of adding more healthy years to human life. and cellular mechanisms underlying ageing and age-related diseases.

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ERIBA | Annual Report V2.indd 7 16-07-2020 21:00 ERIBA is currently the home of 13 research groups that cover a wide range of age-related topics.

Ageing Biology and Stem Cells The aim of studies of Gerald de Haan’s Laboratory is to understand the mechanisms that specify normal hematopoietic stem cell func- tioning from birth to death.

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

Telomeres and Genome Integrity The overall goal of Michael Chang’s Laboratory is to ˡǕɖȸƺȒɖɎɎǝƺȅƺƬǝƏȇǣɀȅɀɖɀƺƳƫɵƏƬƺǼǼɎȒȵȸȒɎƺƬɎǣɎɀǕƺȇȒȅƺ from becoming mutated or inappropriately altered or rearranged.

Cellular and Age-related ɀ Group aims to understand the basic molecular andټxƏȸƬȒ(ƺȅƏȸǣƏ ƬƺǼǼɖǼƏȸȅƺƬǝƏȇǣɀȅɀȒǔƏǕƺǣȇǕًȵƏȸɎǣƬɖǼƏȸǼɵƏɀȵƺƬǣˡƬƬƺǼǼɖǼƏȸɀɎƏɎƺً “senescence”.

Genetic Instability and Ageing The role of genome instability in stem cells in relation to disease pro- cesses and ageing is the main focus of Peter Lansdorp’s group.

Genome Structure Ageing Research at the Laboratory of Victor Guryev is aimed at understand- ing structural changes in human genomes for a better detection of genomic and environmental risks as well as for disease prevention.

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ERIBA | Annual Report V2.indd 8 16-07-2020 21:00 Macromolecules and Interactomes The laboratory of John LaCava focuses broadly on characterizing the contributions of dysregulated macromolecular interactions to dis- eases. To characterize such interactions the group uses combination of biochemical, “omics” and computational approaches.

Asymmetric Cell Division and Ageing Judith Paridaen and her group are focused on understanding how microscopic processes within single stem cells affect their function which is essential to answer how stem cells shape and can help to maintain an healthy body.

Gene Regulation In Ageing and Age-Related Diseases The group of Cor Calkoven is particularly interested in the function of mRNA control elements, protein factors and microRNAs that are involved in mTORC1-controlled processes.

Molecular Neurobiology of Ageing The group led by Ellen Nollen is focused on understanding the mo- lecular mechanisms that drive age-related toxicity of aggregation- prone proteins, which plays a role in age-related diseases like Parkinson and Alzheimer.

Quantitative The group of Maria Colomé-Tatché is interested in understanding the epigenetic changes that take place during the processes of de- velopment, ageing and disease.

Stem Cell Regulation and Mechanisms of Regeneration The Laboratory led by Eugene Berezikov aims at understanding molecular mechanisms that regulate regeneration and activity of stem cells.

Cellular The laboratory of Liesbeth Veenhoff aims for a system wide global characterization of age-related changes, as well as detailed under- standing how the NPCs and cognate transport factors play a role in cellular ageing.

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ERIBA | Annual Report V2.indd 9 16-07-2020 21:00 2019 A Closer Look

This section reports a selected number of achievements that have been accomplished by ERIBA staff in 2019

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ERIBA | Annual Report V2.indd 10 16-07-2020 21:00 11

ERIBA | Annual Report V2.indd 11 16-07-2020 21:00 5EKGNěKĂE Publications

׏ȵƏȵƺȸɀǣȇȸƺȵɖɎƺƳɀƬǣƺȇɎǣˡƬǴȒɖȸȇƏǼɀِהX ɀƬǣƺȇɎǣɀɎɀȵɖƫǼǣɀǝƺƳƏȸƺƬȒȸƳȇɖȅƫƺȸȒǔ»0ًח׎׏אXȇ Many of the published papers were the result of fruitful national and international collabora- tions employing a multidisciplinary approach. Numerous joint projects were initiated within ERIBA, between scientists in ERIBA and research groups at the University Medical Center Groningen and the Faculty of Science and Engineering of the University of Groningen, and ٮɀɎƺƏȅɀƬǣƺȇɎǣˡƬƏƬǝǣƺɮƺȅƺȇɎɀƏȸƺǝǣǕǝǼǣǕǝɎټ ɯǣɎǝǣȇɎƺȸȇƏɎǣȒȇƏǼȵƏȸɎȇƺȸɀِɀȇƏȵɀǝȒɎȒǔ0«X ed below:

Cor Calkhoven’s group In this review the group described the accumulating evidence that CCAAT/enhancer bind- ing protein (C/EBP) transcription factors are determinants of biological age and lifespan. C/ EBPɴ and C/EBPɲ are controlled by the lifespan regulator mechanistic/mammalian target of rapamycin complex 1 (mTORC1) and play an important role in energy homeostasis and adi- ȵȒɀƺɎǣɀɀɖƺƳǣǔǔƺȸƺȇɎǣƏɎǣȒȇِ!ȒȇɮƺȸǕǣȇǕƳƏɎƏƏȸƺƳǣɀƬɖɀɀƺƳًɯǝǣƬǝǣȇƳǣƬƏɎƺɎǝƏɎƏƫƺȸȸƏȇɎ(z methylation can affect ageing via C/EBPɴِ!ǝƏȇǕƺɀǣȇƺȵǣǕƺȇƺɎǣƬ(zȅƺɎǝɵǼƏɎǣȒȇƏȸƺɎǝƺ most promising predictor of biological age and lifespan in humans, but whether methylation changes affect ageing is unresolved. The group discussed the emerging causal nexus be- ٮtween C/EBPɴًƺȇƺȸǕɵȅƺɎƏƫȒǼǣɀȅًƏȇƳ(zƳƺȅƺɎǝɵǼƏɎǣȒȇǣȇȒȸǕƏȇǣɀȅƏǼƏǕƺǣȇǕِXȇƏƳƳǣ tion, they discussed possible roles of other C/EBP members.

ٮNiehrs, C. and Calkhoven, C.F. (2019) The emerging role of C/EBPɴƏȇƳƺȵǣǕƺȇƺɎǣƬ(zȅƺɎǝ ד׏׏ِ׎׎ِח׎׏אǴِɎǣǕِٖה׏׎ِ׏׎׏يX ɵǼƏɎǣȒȇǣȇƏǕƺǣȇǕِÁȸƺȇƳɀJƺȇƺɎً(

Michael Chang’s group Genome mutations are known to accumulate as cells and organisms age, and this has been proposed as a possible causal factor of ageing. What is unclear is whether the rate of spon- taneous mutations is constant during ageing, and whether there are pathways that become ǣȅȵȒȸɎƏȇɎɎȒɀɖȵȵȸƺɀɀɎǝƺƏƬƬɖȅɖǼƏɎǣȒȇȒǔȅɖɎƏɎǣȒȇɀɀȵƺƬǣˡƬƏǼǼɵǣȇƏǕƺƳƬƺǼǼɀِRƺȸƺًɎǝƺ group developed a high-throughput approach to identify genes affecting low-frequency ƺɮƺȇɎɀǣȇɵƺƏɀɎًƏȇƳɖɀƺƳǣɎɎȒˡȇƳǕƺȇƺɀɎǝƏɎɀɖȵȵȸƺɀɀɎǝƺƏƬƬɖȅɖǼƏɎǣȒȇȒǔȅɖɎƏɎǣȒȇɀƳɖȸǣȇǕ yeast ageing. They found that in the absence of PEX19, which encodes a protein required for peroxisome function, the spontaneous mutation rate increases in aged cells. This observation provides a novel link between peroxisomes, genome maintenance, and ageing.

ƺȸǼƺz!ًkƏɿƺȅǣƺȸRJًàƺƺȇǝȒǔǔ zȒɮƏȸǣȇƏ(ًhƏȇɀɀƺȇɀJ0ً ȒǸƺȸȇkً³ƬǝɖɎÁًɮƏȇ ٮɯǣƳƺɀƬȸƺƺȇǣƳƺȇɎǣˡƺɀǕƺȇƺɀɎǝƏɎɀɖȵȵȸƺɀɀɎǝƺƏƬƬɖٮLM, Chang M (2019) ǕƺȇȒȅƺ mulation of spontaneous mutations in young and aged yeast cells. Aging Cell. 2020 Feb;19(2):e13084

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ERIBA | Annual Report V2.indd 12 16-07-2020 21:00 Floris Foijer’s group Chromosomal instability is a common feature in cancer that leads to cells with an abnormal zƬȒȇɎƺȇɎًƏǼɀȒǸȇȒɯȇƏɀƏȇƺɖȵǼȒǣƳɵِXȇƏƳƳǣɎǣȒȇɎȒƏȇƺɖȵǼȒǣƳɵًȒȇǕȒǣȇǕƬǝȸȒȅȒɀȒȅƏǼ) ƬƺǼǼɮƏȸǣƏɎǣȒȇǣȇ(zƬȒȇɎƺȇɎƫƺɎɯƺƺȇǣȇƳǣɮǣƳɖƏǼƬƏȇƬƺȸƬƺǼǼɀِٮɎȒٮǣȇɀɎƏƫǣǼǣɎɵƏǼɀȒǼƺƏƳɀɎȒƬƺǼǼ This CIN contributes to intratumour heterogeneity and clinical response. In this paper, the group investigated chromosomal instability and the resulting karyotype dynamics in primary human colon cancer organoids using time-lapse imaging and single cell sequencing. They found that these tumor organoids display high grade CIN, even those that are associated with a microsatellite instability (MIN) phenotype, which traditionally is seen as a mutually exclusive feature with CIN tumors. The work showed that ongoing CIN is a common feature of colon cancer that shapes the karyotype landscape of these tumors, thus driving its ongoing evolu- tion.

ȒǼǝƏȷɖƺǣȸȒ!Iً¨ȒȇɀǣȒƺȇ ً ƏǸǸƺȸ ًkǼƏƏɀƺȇ³hًkɖƬɖǸǸȒɀƺ0ًɮƏȇhƏƏȸɀɮƺǼƳ«Rًàǣɮǣƻ kǼǣȇǸXًRƏȅǣzً³ȵǣƺȸǣȇǕɀ(!hً³ƏɀƏǸǣzً(ɖɎɎƏ(ً ȒǴ³Iًàȸǣƺɀ«JhًnƏȇɀƳȒȸȵٮhًàƺȸǼƏƏȇ ًIȒǣǴƺȸIً³ȇǣȵȵƺȸɎ ɖƳƺȇƏƏȸƳƺȇً!ǼƺɮƺȸɀRًkȸƏȇƺȇƫɖȸǕ xًɮƏȇƳƺáƺɎƺȸǣȇǕxًɮƏȇ¨ -٣Ongoing chromosomal instability and karyotype evolution in huח׎׏אRhJًkȒȵɀJh¨n٢ ٮזזד׏גɀٖזב׏׎ِ׏׎يƳȒǣِגבזٮגאזي٣ד׏٢דxƏɵٕח׎׏אȅƏȇƬȒǼȒȸƺƬɎƏǼƬƏȇƬƺȸȒȸǕƏȇȒǣƳɀِzƏɎJƺȇƺɎِ 019-0399-6. Epub 2019 Apr 29.

Gerald de Haan’s group In this study, the group demonstrated that the epigenetic reader protein CBX7 possesses the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs) and ƳȒƺɀɀȒƫɵȸƺȵȸƺɀɀǣȇǕǕƺȇƺɀǣȇɮȒǼɮƺƳǣȇƳǣǔǔƺȸƺȇɎǣƏɎǣȒȇً(zƏȇƳƬǝȸȒȅƏɎǣȇȅƏǣȇɎƺȇƏȇƬƺًƏȇƳ cell cycle control. CBX7 is upregulated in acute myeloid leukemia (AML), and showed that its genetic or pharmacological repression in leukemic cells inhibited proliferation and induced differentiation. They revealed several non-histone protein interactions between CBX7 and the ƫǣȇƳǣȇǕȵȸȒɎƺǣȇɀȵȒɀɀƺɀɀٮוÁǝƺɀƺ! æِאȅƺɎǝɵǼɎȸƏȇɀǔƺȸƏɀƺɀ³0Á( ׏ً0RxÁ׏ًƏȇƳ0RxÁחkבR ِבȅƺואkבɎƏȸǕƺɎRוƏɎȸǣȅƺɎǝɵǼƏɎƺƳǼɵɀǣȇƺȵƺȵɎǣƳƺȅȒɎǣǔǝǣǕǝǼɵɀǣȅǣǼƏȸɎȒɎǝƺƬƏȇȒȇǣƬƏǼ! æ -ÁǝƺȸƺɀƺƏȸƬǝǣƳƺȇِוXȇƳƺƺƳًƳƺȵǼƺɎǣȒȇȒǔ³0Á( ׏ǣȇxnƬƺǼǼɀȵǝƺȇȒƬȒȵǣƺƳȸƺȵȸƺɀɀǣȒȇȒǔ! æ ƬƏȇȒȇǣƬƏǼƬȸȒɀɀɎƏǼǸٮȸƺȇƺɯƏǼƏȇƳɖȇƬȒɮƺȸȇȒȇٮƏɀƏȇǣȅȵȒȸɎƏȇɎȸƺǕɖǼƏɎȒȸȒǔɀƺǼǔוɎǣˡƺƳ! æ between distinct pathways, revealing therapeutic opportunities for leukemia.

ً»ɖɀƺȅƏًñɯƏȸɎ0ً³ƬǝƺȵƺȸɀRً(ƺǸǸƺȸxٮhɖȇǕhً ɖǣɀȅƏȇ³!ًáƺƺȸɀǣȇǕ0ً(ƺɎǝȅƺȸɀ nƏɿƏȸƺ³³ًRƏȅȅƺȸǼIً³ǸȒǸȒɮƏçًkȒȒǣɀɎȸƏ³xًkǼƏɖǸƺkً¨ȒȒɎ«ً ɵɀɎȸɵǸǝnàًƳƺRƏƏȇJ (2019)CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions. Cell Rep. 2019 Feb ׎ِד׎׏ِ׎ِח׎׏אǴِƬƺǼȸƺȵِٖה׏׎ِ׏׎׏يƳȒǣِזƺِז׏ח׏ٮה׎ח׏ي٣ו٢האٕא׏

Liesbeth Veenhoff’s group Nuclear Pore Complex (NPC) function in ageing has received much attention in the context of postmitotic (chronologically) ageing cells, such as neurons, and indeed a large body of data now implicate NPC function in neurodegenerative diseases. Veenhoff group studied the fate of NPCs in single dividing yeast cells with the anticipation that the insights may be relevant to ageing of mitotic cells such as stem cells. Overall, their data is consistent with a model where NPC assembly and quality control are compromised in mitotic ageing and where misassem- bled NPCs accumulate in aged cells.

ƺȅȵƺǼXnً!ȸƏȇƺxxًÁǝƏǼǼƺȸ(hًxǣɀǝȸƏًhƏȇɀƺȇ(¨ًhƏȇɀɀƺȇɀJً¨ȒȵǸƺȇ¨ًǸɆǣɎً» -ȇƬǸ¨«ًnɖɀǸ!¨ًàƺƺȇǝȒǔǔnxِ(2019) Age kƏƺƫƺȸǼƺǣȇxًɮƏȇƳƺȸJǣƺɀɀƺȇ0ً³Ɏƺƺȇً dependent deterioration of nuclear pore assembly in mitotic cells decreases transport ِהז׏זגƺnǣǔƺِٖגדדו׏׎ِيƳȒǣِהז׏זגƺيȵǣǣِזٕבhɖȇח׎׏אƳɵȇƏȅǣƬɀِ0Ǽǣǔƺِ

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ERIBA | Annual Report V2.indd 13 16-07-2020 21:00 Peter Lansdorp’s group The mapping of structural genomic variants remains an enormous challenge for current sequencing techniques. Long read technologies such as PacBio have the advantage that mapping to a reference genome is not absolutely required. However, such complete “de ǕƺȇȒȅƺƏɀɀƺȅƫǼɵǣɀȵȸȒƫǼƺȅƏɎǣƬǔȒȸǼƏȸǕƺɀƺǕȅƺȇɎɀȒǔȒɖȸǕƺȇȒȅƺɎǝƏɎƏȸƺˢƏȇǸƺƳƫɵٺȇȒɮȒ ɀƺȷɎƺƬǝȇǣȷɖƺٮǝǣǕǝǼɵȸƺȵƺɎǣɎǣɮƺ(zِÁǝƺǼƏɎɎƺȸƏȸƺƺƏɀǣǼɵƳƺɎƺƬɎƺƳɖɀǣȇǕɎǝƺɀǣȇǕǼƺƬƺǼǼ³ɎȸƏȇƳ developed in the Lansdorp lab. In this paper a combination of PacBio and Strand-seq was used to generate a highly accurate map of a human genome.

àȒǼǼǕƺȸx«ًnȒǕɀƳȒȇJًɖƳƏȇȒ¨ً³ɖǼȒɮƏȸǣً¨ȒȸɖƫɀǸɵ(ً¨ƺǼɖɀȒ¨ًáƺȇǕƺȸxً ȒȇƬƺȵƬǣȒȇJÁًkȸȒȇƺȇƫƺȸǕñzًxɖȇɀȒȇkxً ƏǸƺȸ!ً³ƏȇƳƺȸɀ(ً³ȵǣƺȸǣȇǕɀ(!hً! Lansdorp PM, Surti U, Hunkapiller MW, Eichler EE. (2019) Improved assembly and variant ˡƳƺǼǣɎɵǼȒȇǕȸƺƏƳɀِٮȅȒǼƺƬɖǼƺًǝǣǕǝٮƳƺɎƺƬɎǣȒȇȒǔƏǝƏȵǼȒǣƳǝɖȅƏȇǕƺȇȒȅƺɖɀǣȇǕɀǣȇǕǼƺ Ann Hum Genet. 2019 Nov. doi.org/10.1111/ahg.12364

Marco Demaria’s group is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy ageing and age-related disease (senotherapeutics) has been growing rapidly. Thus, the accurate detection of senescent cells, especially in vivo, is essential. In this ȸƺɮǣƺɯًɎǝƺǕȸȒɖȵƳƺˡȇƺƳƏȇƳƳǣɀƬɖɀɀƺƳǸƺɵƬƺǼǼɖǼƏȸƏȇƳȅȒǼƺƬɖǼƏȸǔƺƏɎɖȸƺɀȒǔɀƺȇƺɀƬƺȇƬƺ ɀǕȸȒɖȵƏǼɀȒټƏȇƳȵȸȒɮǣƳƺȸƺƬȒȅȅƺȇƳƏɎǣȒȇɀȒȇǝȒɯɎȒɖɀƺɎǝƺȅƏɀƫǣȒȅƏȸǸƺȸɀِ(ƺȅƏȸǣƏ ȵȸƺɀƺȇɎƺƳƏȸƺɀȒɖȸƬƺɎȒȒǼɎȒǔƏƬǣǼǣɎƏɎƺɎǝƺǣƳƺȇɎǣˡƬƏɎǣȒȇȒǔǕƺȇƺɀǼǣȇǸƺƳɯǣɎǝɀƺȇƺɀƬƺȇƬƺ (SeneQuest, available at http://Senequest.net). Lastly, they proposed an algorithm to accurately assess and quantify senescence, both in cultured cells and in vivo.

ً ǣɀǝȒȵ!ً!Əȅȵǣɀǣhً!ȒǼǼƏƳȒ JȒȸǕȒɖǼǣɀàًƳƏȅɀ¨(ًǼǣȅȒȇɎǣً ƺȇȇƺɎɎ(!ً ǣɀƬǝȒǔ xً0ɮƏȇǕƺǼȒɖkًIƺȸƫƺɵȸƺJًJǣǼhًRƏȸƏ0ًkȸǣɿǝƏȇȒɮɀǸɵàًhɖȸǸ(ًxƏǣƺȸ ًzƏȸǣɎƏxً zǣƺƳƺȸȇǝȒǔƺȸnً¨ƏɀɀȒɀhIً«Ȓƫƫǣȇɀ¨(ً³ƬǝȅǣɎɎ!ً³ƺƳǣɮɵhًàȒɖǕƏɀkًɮȒȇñǕǼǣȇǣƬǸǣÁً ƺˡȇǣȇǕƏ¨ƏɎǝIȒȸɯƏȸƳِ)يƺǼǼɖǼƏȸ³ƺȇƺɀƬƺȇƬƺ!٣ח׎׏אñǝȒɖ(ً³ƺȸȸƏȇȒxً(ƺȅƏȸǣƏxِ٢ ِד׏׎ِ׎׎ِח׎׏אǴِƬƺǼǼِٖה׏׎ِ׏׎׏يƳȒǣِואזٮב׏זي٣ג٢חו׏ٕ׏בƬɎ ח׎׏אƺǼǼِ!

Ellen Nollen’s group This study, led by former ERIBA staff member Christian Riedel, aimed to identify anti-ageing ƏȇƳǼǣǔƺɀȵƏȇِÈɀǣȇǕȅƏƬǝǣȇƺǼƺƏȸȇǣȇǕȒȇ«zȵȸȒˡǼƺɀȒǔٮƳȸɖǕɀɎȒǣȅȵȸȒɮƺǝɖȅƏȇǝƺƏǼɎǝ ɀɎȸƏɎǣˡƺƳǝɖȅƏȇɎǣɀɀɖƺɀًƬǼƏɀɀǣˡƺȸɀɯƺȸƺǔȒɖȇƳɎǝƏɎƬȒɖǼƳƳǣɀɎǣȇǕɖǣɀǝɵȒɖȇǕǔȸȒȅȒǼƳٮƏǕƺ ח׎בƬǼƏɀɀǣˡƺȸɀɎȒ«zȵȸȒˡǼƺɀȒǔǝɖȅƏȇƬƺǼǼɀɎȸƺƏɎƺƳɯǣɎǝ׏ٮɎǣɀɀɖƺɀِȵȵǼǣƬƏɎǣȒȇȒǔɎǝƺɀƺƏǕƺ ƳǣǔǔƺȸƺȇɎƳȸɖǕɀǼƺƳɎȒɎǝƺǣƳƺȇɎǣˡƬƏɎǣȒȇȒǔɀƺɮƺȸƏǼƬȒȅȵȒɖȇƳɀɎǝƏɎǣȇƳɖƬƺƳɵȒɖɎǝǔɖǼ«z ׎٣ǣȇǝǣƫǣɎȒȸɀȅȒȇȒȸƳƺȇח׎٢RɀȵחȵȸȒˡǼƺɀِÁɯȒȒǔɎǝƺɀƺƬȒȅȵȒɖȇƳɀًɎǝƺǝƺƏɎɀǝȒƬǸȵȸȒɎƺǣȇ and tanespimycin, were selected based on their ability to improve health- and lifespan in the nematode C.elegans. Protection by Hsp90 inhibitors required activation of the unfolded ׎ǣȇǝǣƫǣɎȒȸɀƏȸƺǸȇȒɯȇɎȒȵȸȒɎƺƬɎƏǕƏǣȇɀɎƬǝȸȒȇǣƬǣȇˢƏȅȅƏɎǣȒȇƏȇƳחȵȸȒɎƺǣȇȸƺɀȵȒȇɀƺِɀRɀȵ senescence, their improving protein homeostasis as proposed in this study would add yet another mode of geroprotection. Future work in humans will be required to determine their therapeutic potential.

ȸǣȑȒnًkƏɮɄƺǸً³ƺȇXً³ƺǣȇɀɎȸƏ«Xً³ɎȸȒɖɀɎȸɖȵzًzȒǼǼƺȇ0ًٮhƏȇɀɀƺȇɀJ0ًnǣȇææًxǣǼǼƏȇ ƏɀƺƳ³ƬȸƺƺȇǣȇǕXƳƺȇɎǣˡƺɀ¨ǝƏȸȅƏƬȒǼȒǕǣƬƏǼXȇǝǣƫǣɎǣȒȇ ٮ٣ÁȸƏȇɀƬȸǣȵɎȒȅǣƬɀח׎׏א٢ Riedel CG Ǵِٖה׏׎ِ׏׎׏يƳȒǣِה׎ِƺזגٮוהגي٣א٢ואٕחȵȸח׎׏א׎ƏɀƏxƺƏȇɀɎȒ(ƺǔƺȸǕƺǣȇǕِ!ƺǼǼ«ƺȵِחȒǔRɀȵ celrep.2019.03.044.

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ERIBA | Annual Report V2.indd 14 16-07-2020 21:00 Eugene Berezikov’s group In this work we systematically investigated how different culture temperatures can affect the ƫǣȒǼȒǕɵȒǔɎǝƺȸƺǕƺȇƺȸƏɎǣȇǕˢƏɎɯȒȸȅȅȒƳƺǼȒȸǕƏȇǣɀȅxƏƬȸȒɀɎȒȅɖȅǼǣǕȇƏȇȒِáƺɀǝȒɯɎǝƏɎ altering temperature conditions can be used to reduce the time required to establish M. lig- nano cultures, perform RNAi experiments, store important lines, and optimize microinjection ȵȸȒƬƺƳɖȸƺɀǔȒȸɎȸƏȇɀǕƺȇƺɀǣɀِÁǝƺɀƺˡȇƳǣȇǕɀɯǣǼǼǝƺǼȵɎȒȒȵɎǣȅǣɿƺɎǝƺƳƺɀǣǕȇȒǔƺɴȵƺȸǣȅƺȇɎɀǣȇ M. lignano, and thus facilitate future research using this model organism.

٣XȇˢɖƺȇƬƺȒǔɎƺȅȵƺȸƏɎɖȸƺȒȇח׎׏אáɖƳƏȸɀǸǣhًÈɀɎɵƏȇɎɀƺɮkًJǼƏɿƺȇƫɖȸǕnً ƺȸƺɿǣǸȒɮ0٢ -ƳƺɮƺǼȒȵȅƺȇɎًȸƺȵȸȒƳɖƬɎǣȒȇƏȇƳȸƺǕƺȇƺȸƏɎǣȒȇǣȇɎǝƺˢƏɎɯȒȸȅȅȒƳƺǼȒȸǕƏȇǣɀȅًxƏƬȸȒɀ -ƺ!ȒǼǼƺƬِהٮאא׎׏ٮח׎׏ٮ׏דז׎גɀٖהז׏׎ِ׏׏يƳȒǣِוيדٕאIƺƫ׏ח׎׏אɎȒȅɖȅǼǣǕȇƏȇȒِñȒȒǼȒǕǣƬƏǼnƺɎɎِ tion 2019.

Victor Guryev’s group Affordable sequencing has greatly advanced our understanding of changes in transcrip- tion programs and their relation to ageing and diseases. The typical analysis of gene expres- ɀǣȒȇƳƏɎƏǔȒƬɖɀƺɀȒȇɎǝƺˡȇƳǣȇǕȒǔǕƺȇƺɀɎǝƏɎɀǝȒɯƳǣǔǔƺȸƺȇɎǣƏǼƺɴȵȸƺɀɀǣȒȇƫƺɎɯƺƺȇȵƏɎǣƺȇɎ groups. Unfortunately, in such analysis, variability in gene expression is often ignored as it is treated as a nuisance that only diminishes statistical power. At the same time, gene expres- ɀǣȒȇǣɀȇƏɎɖȸƏǼǼɵƏɀɎȒƬǝƏɀɎǣƬȵȸȒƬƺɀɀًƏȇƳǣȇɀȒȅƺƬƏɀƺɀǣɎɀˢɖƬɎɖƏɎǣȒȇًȸƏɎǝƺȸɎǝƏȇɎǝƺȅƺƏȇ -zƬȒȵɵȇɖȅƫƺȸًƬȒɖǼƳƫƺɀǣǕȇǣˡƬƏȇɎǼɵǣȇˢɖƺȇƬƺƳƫɵƏȇƺɴȵƺȸǣȅƺȇɎƏǼǔƏƬɎȒȸȒȸƏȵǝɵɀǣ» -ɀǕȸȒɖȵƳǣɀƬɖɀɀƺƳƏȵȵȸȒƏƬǝƺɀɎȒȷɖƏȇɎǣˡƬƏɎǣȒȇȒǔƺɴȵȸƺɀټȒǼȒǕǣƬƏǼɀɎƏɎƺِXȇɎǝǣɀȵƏȵƺȸJɖȸɵƺɮ sion variability, its contribution to understanding of the principles underlying physiological homeostasis, and its potential to uncover additional molecular phenotypes associated with age-related diseases.

de Jong TV, Moshkin YM, Guryev V (2019) Gene expression variability: the other dimen- ٖאד׏׎ِ׏׏يƳȒǣِזד׏ٮדג׏ي٣ד׏٢דxƏɵ׏ٕח׎׏אɀǣȒȇǣȇɎȸƏȇɀƬȸǣȵɎȒȅƺƏȇƏǼɵɀǣɀِ¨ǝɵɀǣȒǼJƺȇȒȅǣƬɀِ ِדxƏȸ׏ח׎׏א0ȵɖƫِז׎׏אِזאȵǝɵɀǣȒǼǕƺȇȒȅǣƬɀِ׎׎׏

John LaCava’s group zɀƺȷɖƺȇƬƺɀɎǝƏɎǝƏɮƺɎǝƺƏƫǣǼǣɎɵɎȒȸƺȵǼǣƬƏɎƺɎǝƺȅɀƺǼɮƺɀǣȇ)ټɀƺǼˡɀǝټƺɎȸȒɎȸƏȇɀȵȒɀȒȇɀƏȸƺ» host genomes via a ‘copy and paste’ mechanism. The proliferation of LINE-1 retrotransposons is apparent at the genetic level in cancers and cell lines – providing unequivocal evidence for the expression of the enzymatic, replicative component of LINE-1: ORF2p. However, ORF2p continues to elude direct detection. LaCava’s group and their collaborators took a deep dive into data from the NCI’s Clinical Proteomic ȵȵƺȵɎǣƳƺɀǣǕȇƏɎɖȸƺɀِIƏǣǼǣȇǕɎȒˡȇƳƬȒȇɮǣȇƬǣȇǕא«I ÁɖȅȒȸȇƏǼɵɀǣɀ!ȒȇɀȒȸɎǣɖȅǣȇɀƺƏȸƬǝȒǔ evidence in the archived data, they raised a collection of monoclonal antibodies against the protein in an effort to bolster capture and detection. Although the antibodies validated excel- lently against the target in ectopic expression, endogenous ORF2p remained elusive. Finally, -«I׏ȵًƳǣȸƺƬɎǼɵǔȸȒȅȸƺɀƺƬɎƺƳȵƏ ׏«z¨ɀًɮǣƏٮɎǝƺɵɎȒȒǸɎȒƏǔˡȇǣɎɵǣɀȒǼƏɎǣȇǕƺȇƳȒǕƺȇȒɖɀnXz0 ׏ƬƏȇƬƺȸǣȇɎƺȸƏƬɎȒȅƺِǼɎǝȒɖǕǝٮɎǣƺȇɎƬȒǼȒȸƺƬɎƏǼƬƏȇƬƺȸɀ٫ȸƺȵȒȸɎǣȇǕɎǝƺˡȸɀɎƺȇƳȒǕƺȇȒɖɀnXz0 ǣɀȒǼƏɎƺƳȵȸȒɎƺǣȇɀًɎǝƺɵƳƺȅȒȇɀɎȸƏɎƺƳɎǝƺɎƺƬǝȇǣƬƏǼٮȵɯƏɀȇȒɎǣƳƺȇɎǣˡƺƳƏȅȒȇǕɎǝƺƬȒאI» feasibility of studying disease-related protein complexes directly in patient tumors and identi- ׏ƬȒǼȒȸƺƬɎƏǼƬƏȇƬƺȸȵȸȒɎƺǣȇǣȇɎƺȸƏƬɎǣȒȇɀƏȇƳɎǝȒɀƺٮˡƺƳȒɮƺȸǼƏȵɀƫƺɎɯƺƺȇƺȇƳȒǕƺȇȒɖɀnXz0 ÁƬƺǼǼɀِÁǝƺɵƬȒȇƬǼɖƳƺƳɎǝƏɎבחאٮ׏ƺɴȵȸƺɀɀǣȇǕR0kٮȵȸƺɮǣȒɖɀǼɵƳƺɀƬȸǣƫƺƳǔȸȒȅƺƬɎȒȵǣƬnXz0 more sensitive methods will be needed to robustly detect ORF2p and propose targeted mass ˢɖȒȸƺɀƬƺȇƬƺƏɀɎɯȒǔɖɎɖȸƺƳǣȸƺƬɎǣȒȇɀِٮɀȵƺƬɎȸȒȅƺɎȸɵƏȇƳȵȸȒɴǣȅǣɎɵǼǣǕƏɎǣȒȇǣȅȅɖȇȒ

ǕǝƫƏǣƺًxًِÁƏɵǼȒȸًxًِRɖɀƫƏȇƳً(ًِ(ƺɀǝȵƏȇƳƺًàًِ³ɎƺȸƏȇǸƏًhًِ ȸƳƺǼǴƏȇً(ًِáƏȇǕًæًِ -JȒȸƫȒɖȇȒɮًxًِçƏȇǕًáًِ³ǣƺً ًِnƏȸȅƏȇًRًِhǣƏȇǕًRًِxȒǼǼȒɵًkًِǼɎɖǸǝȒɮًXًِnǣًñًِxƬkƺȸ -ȸȒɯًáًِIƺȇɵȜً(ًِ ɖȸȇɀًkًِnƏ!ƏɮƏًhِ(2020). LINE-1 ORF2p expression is nearly imper ٮח׎׏ٮ׏׎׎בɀ׏ٖהזƳɴِƳȒǣِȒȸǕٖ׏׎ِ׏׏ٖٖيǝɎɎȵɀِח׏ٮƬƺȵɎǣƫǼƺǣȇǝɖȅƏȇƬƏȇƬƺȸɀِxȒƫǣǼƺ(z׏׏٢׏٣ً׏ 0191-2

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ERIBA | Annual Report V2.indd 15 16-07-2020 21:00 Grants

In 2019 ERIBA secured €2.77 million from grants. This included prestigious grants from the ɖɎƬǝ!ƏȇƬƺȸ³ȒƬǣƺɎɵًñȒȇxɯًƏȇƳɎǝƺn³ǔȒɖȇƳƏɎǣȒȇِÁǝƺǣȇɀɎǣɎɖɎƺƏǼɀȒȸƺƬƺǣɮƺƳƏǕȸƏȇɎɎȒ) ȵȸǣɮƏɎƺȸƺɀƺƏȸƬǝِ(ƺɎƏǣǼƺƳǣȇǔȒȸȅƏɎǣȒȇƏƫȒɖɎ0«X ǕȸƏȇɎɀƏȇƳǔɖȇƳǣȇǕƬƏȇƫƺٮƫȒǼɀɎƺȸȵɖƫǼǣƬ found on page 32

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ERIBA | Annual Report V2.indd 16 16-07-2020 21:00 Awards

Victor Guryev’s team from ERIBA together with a RUG team (RNA TORCH) won the BioHack 2019 award. The team received an award at the bioinformatics hackathon held in Saint Petersburg, Russia. Teams consisting of biologists and programmers participated in the event to solve one of 40 problems within 48 hours.

Glòria Casas Gimeno,¨ǝ(ɀɎɖƳƺȇɎǣȇɎǝƺ¨ƏȸǣƳƏƺȇǼƏƫًȸƺƬƺǣɮƺƳƏ¨ȒɀɎƺȸ¨ȸǣɿƺƏɎɎǝƺR XJ³ International Winter School on “Molecular Mechanisms in Mitosis”. Glòria presented a poster Ȓȇǝƺȸ¨ǝ(ȵȸȒǴƺƬɎȒȇɎǝƺȸȒǼƺȒǔƬƺǼǼɖǼƏȸƬƺȇɎȸǣȒǼƺɀǣȇƏɀɵȅȅƺɎȸǣƬɀɎƺȅƬƺǼǼƳǣɮǣɀǣȒȇِ³ǝƺƏǼɀȒ ȸƺƬƺǣɮƺƳƏȇȒɎǝƺȸȵȒɀɎƺȸȵȸǣɿƺǣȇXȇɎƺȸȇƏɎǣȒȇƏǼ!ȒȇǔƺȸƺȇƬƺȒȇƬǣǼǣƏًˢƏǕƺǼǼƏƏȇƳ!ƺȇɎȸȒɀȒȅƺɀً Imagine Institute, Paris.

ÁȸƏɮƺǼƏɯƏȸƳɎȒƏɎɎƺȇƳ kƏɎɵƏ(ɮȒȸǣƏȇǣȇȒɮƏً¨ǝ(ɀɎɖƳƺȇɎǣȇ¨ƏȸǣƳƏƺȇǼƏƫȸƺƬƺǣɮƺƳ0x IȸȒȅ(ƺɀǣǕȇɎȒ!ƺǼǼ³ǣǕȇƏǼǼǣȇǕɎȒÁǣɀɀɖƺxȒȸȵǝȒǕƺȇƺɀǣɀٮȵɎȒǕƺȇƺɎǣƬɀ ȵȸƏƬɎǣƬƏǼƬȒɖȸɀƺ 0x at EMBL Heidelberg, Germany.

ɀǕȸȒɖȵȸƺƬƺǣɮƺƳ!ƏȇƬƺȸ«ƺɀƺƏȸƬǝ!ƺȇɎƺȸJȸȒȇǣȇǕƺȇټSonja Buisman,¨ǝ(ɀɎɖƳƺȇɎǣȇƳƺRƏƏȇ (CRCG) prize for best short-pitch.

ɀǕȸȒɖȵȸƺƬƺǣɮƺƳ!ƏȇƬƺȸ«ƺɀƺƏȸƬǝ!ƺȇɎƺȸJȸȒȇǣȇǕƺȇټSabrina Jacobsً¨ǝ(ɀɎɖƳƺȇɎǣȇƳƺRƏƏȇ (CRCG) prize for best short-pitch.

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ERIBA | Annual Report V2.indd 17 16-07-2020 21:00 Graduations

ǔȒɖȸɵȒɖȇǕɀƬǣƺȇɎǣɀɎɀǕȸƏƳɖƏɎƺƳǔȸȒȅ0«X Əɀ¨ǝ(ɀɎɖƳƺȇɎɀƏȇƳɀǣȇƬƺǝƏɮƺȅȒɮƺƳًח׎׏אXȇ to new positions either in academia or industry: ɀǼƏƫ٣ǣɀƬɖȸȸƺȇɎǼɵƏɎɎǝƺ«ǣǴǸɀǣȇɀɎǣɎɖɖɎɮȒȒȸټƺȅƏȸǣƏ)Alejandra Hernandez Segura٢ Volksgezondheid en Milieu (RIVM), The Netherlands, Irina Rempel (Veenhoff’s lab) is at Novartis, Basel, Switzerland, Paula van Mourik (Chang’s lab) is at EV Biotech, Groningen, The Netherlands, Tristan de Jong (Guryev’s lab) is self-employed.

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ERIBA | Annual Report V2.indd 18 16-07-2020 21:00 5EKGNěKĂE&KSSGMKNCěKON and Outreach

X ǝƏɀƫƺƺȇƏƬɎǣɮƺǼɵǣȇɮȒǼɮƺƳǣȇɀƬǣƺȇɎǣˡƬƳǣɀɀƺȅǣȇƏɎǣȒȇƏȇƳȵɖƫǼǣƬȒɖɎȸƺƏƬǝِÁǝƺˡȸɀɎ»0 Career day organised in 2018 was a huge success with contributions from people from both academia and industry. On Wednesday 24 April 2019, the second edition of the ERIBA Career ƏɵɎȒȒǸȵǼƏƬƺًɯǝƺȸƺ¨ǝ(ɀɎɖƳƺȇɎɀƏȇƳ¨ȒɀɎƳȒƬɀƺɴȵǼȒȸƺƳƬƏȸƺƺȸȒȵȵȒȸɎɖȇǣɎǣƺɀȒɖɎɀǣƳƺȒǔ) ׎¨ǝ(ɀɎɖƳƺȇɎɀƏȇƳȵȒɀɎƳȒƬɀǔȸȒȅ0«X ƏȇƳɎǝƺÈx!JƏɎɎƺȇƳƺƳɎǝƺהƏƬƏƳƺȅǣƏِxȒȸƺɎǝƏȇ meeting. The scientists at ERIBA are committed to many outreach activities and nurturing the young ȅǣȇƳɀɎȒƫɖǣǼƳɎǝƺɀƬǣƺȇɎǣɀɎɀȒǔɎȒȅȒȸȸȒɯِkƺƺȵǣȇǕȒɖȸƬȒȅȅǣɎȅƺȇɎɎȒɎǝƺƬƏɖɀƺɯƺȒȵƺȇƺƳ ȒɖȸƳȒȒȸɀɎȒɎǝƺȵɖƫǼǣƬɎȒɀǝƏȸƺɀƬǣƺȇɎǣˡƬǸȇȒɯǼƺƳǕƺƏɎɎǝƺñȵƏȇȇƺȇƳñƺȸȇǣǸƺƺɮƺȇɎِxȒȸƺ ׎ȵƺȒȵǼƺƏɎɎƺȇƳƺƳɎǝƺƺɮƺȇɎƏȇƳƺȇǴȒɵƺƳɎǝƺɀƬǣƺȇɎǣˡƬƺɮƺȇɎɀɀȵƺƬǣˡƬƏǼǼɵɎƏǣǼȒȸƺƳɎȒזהɎǝƏȇ them. ɀȒɖɎȸƺƏƬǝƬȒȅȅǣɎɎƺƺټ ÁȒǼǣȇǸɀƬǣƺȇɎǣˡƬȸƺɀƺƏȸƬǝًɀƬǣƺȇɎǣˡƬȒɖɎȸƺƏƬǝًƏȇƳƺƳɖƬƏɎǣȒȇ0«X member developed “Science in a Box” concept. This concept was designed to trigger student ƬɖȸǣȒɀǣɎɵƏȇƳɎȒƺȇƬȒɖȸƏǕƺɎǝƺɀɎɖƳƺȇɎɀɎȒɯƏȸƳɀƏɀƬǣƺȇɎǣˡƬƬƏȸƺƺȸِÁǝƺǣƳƺƏƫƺǝǣȇƳɎǝƺ concept was to have a science experiment, specially designed for school students enclosed in a box. As part of the Science Fair ‘University of Noorderzon’ organized by the Young Academy Groningen the ERIBA scientists imparted research knowledge to kids and their parents. To further enhance the outreach, and to explain the importance of animals in research our scientist presented in the summer school Healthy ageing, and ERIBA hosted a visit for high ñƺƫȸƏˡɀǝِɎ0«X ƫȒɎǝيɀƬǝȒȒǼɀɎɖƳƺȇɎɀɎȒɎƺƏƬǝɎǝƺȅƏƫȒɖɎȒȇƺȒǔȒɖȸƏȇǣȅƏǼȅȒƳƺǼɀ experienced scientists and young scientists of tomorrow actively participate in outreach ɀƬǣƺȇɎǣˡƬٹƺɮƺȇɎɀِÁȒɎǝǣɀƬƏɖɀƺًɎǝƺɵȒɖȇǕɀƬǣƺȇɎǣɀɎɀƏɎ0«X ȸƺȵȸƺɀƺȇɎƺƳɎǝƺǣȇɀɎǣɎɖɎƺƏɎ ƳƺǼǣɮƺȸǣȇǕǣȇɎƺȸƺɀɎǣȇǕɀƬǣƺȇɎǣˡƬǼƺƬɎɖȸƺɀɎȒɎǝƺǕƺȇƺȸƏǼȵɖƫǼǣƬƏɎȒȇƺȒǔɎǝƺǼƏȸǕƺɀɎًٺȵɖƫƬȸƏɯǼ science festivals (www.pintofscience.nl). ÁȒɀɎǣȅɖǼƏɎƺȇƺɯǣƳƺƏɀƏȇƳɎȒǔȒɀɎƺȸɀƬǣƺȇɎǣˡƬƬȒǼǼƏƫȒȸƏɎǣȒȇɀǣȇɎǝƺȸƏȵǣƳǼɵǕȸȒɯǣȇǕˡƺǼƳȒǔ ageing research ERIBA organised the 3rd Molecular Biology of Ageing meeting. This meeting was attended by people from all across the globe and was a huge success. ǔȒȸȅȒȸƺƳƺɎƏǣǼɀِדד³ƺƺȵƏǕƺ

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ERIBA | Annual Report V2.indd 19 16-07-2020 21:00 Facts and Figures

Looking back to 2019 mahn`a_Z\mlZg]Û`nk^l

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ERIBA | Annual Report V2.indd 20 16-07-2020 21:00 21

ERIBA | Annual Report V2.indd 21 16-07-2020 21:00 5EKGNěKĂE Publications

SCIENTIFIC PUBLICATIONS 2019 61

2011 - 12 2015 - 39 2012 - 22 2016 - 40 2013 - 37 2017 - 55 2014 - 34 2018 - 58

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ERIBA | Annual Report V2.indd 22 16-07-2020 21:00 Publications per Research Group

Laboratory of Gene Regulation in Ageing and Age-related Diseases Group Leader: Cor Calkhoven

ƬǸƺȸȅƏȇȇÁًRƏȸɎǼƺƫƺȇJًxɜǼǼƺȸ!ًxƏɀɎȸȒƫɖȒȇǣJًJȸȒɎǝxً³ɎƺȸǸƺȇ ًñƏǣȇǣxً .1 çȒɖɀɀƺǔ³ًñɖǣƳǝȒǔR«ًkȸƏɖɀɀ³«ًkȒȸɎȅƏȇJًƳƺRƏƏȇJًƳƺ ȸɖǣȇًáƏȇǕñª ǼƏɎɿƺȸxًkƺȅȵƏ³ًCalkhoven CF. (2019) C/EBPɴ-LIP induces cancer-type metabolic¨ reprogramming by regulating the let-7/LIN28B circuit in mice. Commun Biol. 2019 Jun 14;2:208. doi: 10.1038/s42003-019-0461-z. eCollection 2019.

2. Niehrs, C. and Calkhoven, C.F. (2019) The emerging role of C/EBPɴƏȇƳƺȵǣǕƺȇƺɎǣƬ(z ד׏׏ِ׎׎ِח׎׏אǴِɎǣǕِٖה׏׎ِ׏׎׏يX methylation in ageing.ÁȸƺȇƳɀJƺȇƺɎً(

Xًِ ȒȸƬǝhƺȇɀƺȇًxًِٮƏǸɖǼƏً(ًِƫǼƏɀɀƺȸًًِǕɖɿɿǣًًِȇɎƺƫǣًًِ ƏȸɿǣǼƏǣًzًِ ǣɎɎȇƺȸًx .3 Calkhoven, C.F.ً!ǝƺȇً(ًِƳƺJȸƺɵًِ(ِzِhًِIƺǣǕƺًhِzًِJƺȒȸǕǣƺɮɀǸƏɵƏًًِJǼƏƳɵɀǝƺɮً àِzًِJȒǼƏɎȒًÁًِJɖƳǸȒɮًِàًِRȒȵȵƺًÁًِkƏƺƫƺȸǼƺǣȇًxًِkƏɎƏǴǣɀɎȒً¨ًِkƺȇȇƺƳɵً ِkًِnƏǼً ًِ!ِ)ɿƺȸȒɮًXًِ¨ƺɎȸًxًِِ«ƺƏɀȒȇً«ɖƫǣȇɀɿɎƺǣȇً àǣǼǼƏǼƫƏًًِxȒɀǸƏǼƺɮًًِِٮÈًِxƏȸɎǣȇ ٣Latestח׎׏אkȇɖƳɀƺȇًxِ٢ٮÁɵɀǝǸȒɮɀǸǣɵًًِàƏȇǝƏƺǼƺȇًªًِñǝƏɮȒȸȒȇǸȒɮًًِ³Ƭǝƺǣƫɵƺ וזגאƏǕǣȇǕِ׏׎ٖאבהז׏׎ِ׏يX advances in ageing research and drug discovery.ǕǣȇǕً(

Laboratory of Molecular Neurobiology of Ageing Group Leader: Ellen Nollen

ً¨Sorgdrager FJH, Vermeiren Y, Van Faassen M, van der Ley C, Nollen EAA,kƺȅƏX .1 ɀȵƺƬǣˡƬƬǝƏȇǕƺɀȒǔɎǝƺǸɵȇɖȸƺȇǣȇƺȵƏɎǝɯƏɵǣȇٮƏȇƳƳǣɀƺƏɀƺٮ٣Ǖƺח׎׏א٢ِ¨¨ƺ(ƺɵȇ) ׏׎ِ׏׏׏׏ٖيƳȒǣِזההٮהדהي٣ד׏٢דƺƬٕ׏)ח׎׏אParkinson's and Alzheimer's disease.hzƺɖȸȒƬǝƺȅِ ِדאɖǕח׎׏א0ȵɖƫِבגזגǴȇƬِ׏

,nƏǣȇƺ«Iً³ǣȇȇǣǕƺÁًxƏkçًRƏƏƬǸhً¨ȒɖƳƺǼ!ًJƏǣƳƏ¨ً!ɖȸȸɵzً¨ƺȸȇǣxًNollen EAA .2 ٣Fast Fluorescenceח׎׏אȒƫɀȒȇ!xًàƺȇƳȸɖɀƬȒǼȒxًkƏȅǣȇɀǸǣ³ƬǝǣƺȸǼƺJ³ًkƏȅǣȇɀǸǣ!Iِ٢) Lifetime Imaging Reveals the Aggregation Processes of iɲ-Synuclein and Polyglutamine in Aging Caenorhabditis elegans. ACS Chem Biol. 2019 Jul 19;14(7):1628-1636. doi: 10.1021/ ِואhɖȇח׎׏א0ȵɖƫِגדבƫ׎׎חƏƬɀƬǝƺȅƫǣȒِ

,ȸǣȑȒnًkƏɮɄƺǸً³ƺȇXً³ƺǣȇɀɎȸƏ«Xً³ɎȸȒɖɀɎȸɖȵzًNollen EAAٮhƏȇɀɀƺȇɀJ0ًnǣȇææًxǣǼǼƏȇ .3 ƏɀƺƳ³ƬȸƺƺȇǣȇǕXƳƺȇɎǣˡƺɀ¨ǝƏȸȅƏƬȒǼȒǕǣƬƏǼXȇǝǣƫǣɎǣȒȇ ٮRiedel CG (2019) ÁȸƏȇɀƬȸǣȵɎȒȅǣƬɀ .׎ƏɀƏxƺƏȇɀɎȒ(ƺǔƺȸǕǣȇǕِ Cell Rep. 2019 Apr 9;27(2):467-480.e6. doi: 10.1016/jחȒǔRɀȵ celrep.2019.03.044.

kȒȒȵȅƏȇxً³ƺǣȇɀɎȸƏ«XًNollen EAA.(2019) C. elegans as a Model for Synucleinopathies .4 .Tools and Techniques. Methods Mol Biol يɎǝƺȸzƺɖȸȒƳƺǕƺȇƺȸƏɎǣɮƺ(ǣɀƺƏɀƺɀ ƏȇƳ 2019;1948:93-112. doi: 10.1007/978-1-4939-9124-2_9.

Platten M, Nollen EAA, Röhrig UF, Fallarino F, Opitz CA. (2019) Tryptophan metabolism as ِד a common therapeutic target in cancer, neurodegeneration and beyond.zƏɎ«ƺɮ(ȸɖǕ ƺɮǣƺɯِ»ِדٮה׎׎׏ٮח׎׏ٮבוד׏גɀٖזב׏׎ِ׏׎ي׎׏ِƳȒǣגٮחובي٣ד٢זxƏɵٕ׏ח׎׏אǣɀƬȒɮِ)

kȒȒȵȅƏȇxًRƺɎɿ!ًNollen EAA (2019).Saved by the Matrix: UPR Independent Survival .6 under ER Stress. Cell. 2019 Nov 27;179(6):1246-1248 doi:10.1016/j.cell.2019.11.012.

Tryptophan ٣ח׎׏א٢¨¨³ȒȸǕƳȸƏǕƺȸIhRًzƏɖƳƻ¨háًkƺȅƏX¨ًNollen EAً(ƺɵȇ .7 .IȸȒȅ ǣȒȅƏȸǸƺȸɎȒÁǝƺȸƏȵƺɖɎǣƬÁƏȸǕƺɎِ Front ImmunolيxƺɎƏƫȒǼǣɀȅǣȇXȇˢƏȅȅƏǕǣȇǕ ِח׎׏אƺ!ȒǼǼƺƬɎǣȒȇِדהדא׎ِח׎׏אˡȅȅɖِٖחזבב׏׎ِيƳȒǣِדהדאي׎ٕ׏׎בƬɎ

23

ERIBA | Annual Report V2.indd 23 16-07-2020 21:00 Laboratory of Stem cell regulation and mechanisms of regeneration Group Leader: Eugene Berezikov

nȒǕƺɀxًRƏȇٮǼǣɮƺǣȸƏkx!ً ƏȸǸƺȸhRًBerezikov Eً¨ǣȇƳɖȸnًkɵȇǣǕȒȵȒɖǼȒɀ³ً0ǣɀƬǝƺȇ .1 ٣Electrical stimulation shifts healing/scarringח׎׏אñً ǝƏɮɀƏȸx ًRƺȇȸǣƬǝ(ًnƺȵȵǣǸnِ٢ towards regeneration in a rat limb amputation model. Sci Rep. 2019 Aug 7;9(1):11433. doi: ɯِٮחזבוגٮח׎׏ٮזחד׏גɀٖזב׏׎ِ׏׎

2. Ramm SA, Lengerer B, Arbore R, Pjeta R, Wunderer J, Giannakara A, Berezikov E, Ladurner P, Schärer L. (2019)Sex allocation plasticity on a transcriptome scale: Socially يX )ודז׏חז׎בي)sensitive gene expression in a simultaneous hermaphrodite.¨xX ِאxƏɵח׎׏א0ȵɖƫٖוו׎דȅƺƬِ׏

áɖƳƏȸɀǸǣhًÈɀɎɵƏȇɎɀƺɮkًJǼƏɿƺȇƫɖȸǕnًBerezikov E (2019) XȇˢɖƺȇƬƺȒǔɎƺȅȵƺȸƏɎɖȸƺ .3 ȒȇƳƺɮƺǼȒȵȅƺȇɎًȸƺȵȸȒƳɖƬɎǣȒȇƏȇƳȸƺǕƺȇƺȸƏɎǣȒȇǣȇɎǝƺˢƏɎɯȒȸȅȅȒƳƺǼȒȸǕƏȇǣɀȅً ِהٮאא׎׏ٮח׎׏ٮ׏דז׎גɀٖהז׏׎ِ׏׏يƳȒǣِוيדٕאIƺƫ׏ח׎׏אMacrostomum lignano.ñȒȒǼȒǕǣƬƏǼnƺɎɎِ eCollection 2019.

24

ERIBA | Annual Report V2.indd 24 16-07-2020 21:00 Laboratory of Genomic Instability in Development and Disease Group Leader: Floris Foijer

ȒǼǝƏȷɖƺǣȸȒ!Iً¨ȒȇɀǣȒƺȇ ً ƏǸǸƺȸ ًkǼƏƏɀƺȇ³hًkɖƬɖǸǸȒɀƺ0ًɮƏȇhƏƏȸɀɮƺǼƳ«Rًàǣɮǣƻ .1 kǼǣȇǸXًRƏȅǣzً³ȵǣƺȸǣȇǕɀ(!hً³ƏɀƏǸǣzً(ɖɎɎƏ(ً ȒǴ³Iًàȸǣƺɀ«JhًnƏȇɀƳȒȸȵٮhًàƺȸǼƏƏȇ ًFoijer F, Snippert ɖƳƺȇƏƏȸƳƺȇً!ǼƺɮƺȸɀRًkȸƏȇƺȇƫɖȸǕ xًɮƏȇƳƺáƺɎƺȸǣȇǕxًɮƏȇ¨ ٣Ongoing chromosomal instability and karyotype evolution inח׎׏אRhJًkȒȵɀJh¨n٢ ٖזב׏׎ِ׏׎يƳȒǣِגבזٮגאזي٣ד׏٢דxƏɵٕח׎׏אhuman colorectal cancer organoids.zƏɎJƺȇƺɎِ ِחאȵȸח׎׏א0ȵɖƫِהٮחחב׎ٮח׎׏ٮזזד׏גɀ

2. Pillay N, Tighe A, Nelson L, Littler S, Coulson-Gilmer C, Bah N, Golder A, Bakker B, ,ǕǣǼɮǣƺ(hًFoijer F ³ȵǣƺȸǣȇǕɀ(!hًhƏȅƺɀ(Xً³ȅǣɎǝkxًhȒȸƳƏȇxًxȒȸǕƏȇ«(ً ɮƏȸǣƏȇ!ƏȇƬƺȸ z«ƺȵǼǣƬƏɎǣȒȇàɖǼȇƺȸƏƫǣǼǣɎǣƺɀ«ƺȇƳƺȸ)٣ח׎׏אhƏƬǸɀȒȇ(ًÁƏɵǼȒȸ³³ِ٢ ǣƫȒɀƺ٣JǼɵƬȒǝɵƳȸȒǼƏɀƺXȇǝǣƫǣɎȒȸɀِ Cancer Cell. 2019 Mar»ٮ¨)ƺǼǼɀ³ƺȇɀǣɎǣɮƺɎȒ¨ȒǼɵ٢! ِג׎׎ِא׎ِח׎׏אǴِƬƬƺǼǼِٖה׏׎ِ׏׎׏يƳȒǣِזƺِבבדٮח׏דي٣ב٢דבٕז׏

ɿǣɿkًnǣȅɿƺȸɯƏǼƏhIً³ɎɖȸȅǼƺƬǝȇƺȸXًRɖȸǼƺɵ0ًñǝƏȇǕ!ًhƺǕƏȇƏɎǝƏȇk ًzƺǼɀȒȇJً .3 ٔ ȸǣƺȇ(«ًkȒƬǝƺȸhًçȒɖɀɀƺǔ³ًɮƏȇ«ƺƺ ًɮƏȇ(ƺɖȸɀƺȇ0hً ȸȒȇǸ³ًIǣƺȸȸȒàƺǼƏɀƬȒ« JH, de Bruin A, van den Bos H, , Foijer F, van de Sluis B, Roberts LR, Gores GJ, Li H, van ٣Overexpression Causes Chromosome Instability in Liver Cellsח׎׏אƺɖȸɀƺȇhx!Ƭȇƺ׏٢) يƳȒǣِאƺ׏ِהאאٮ׏׎אي٢׏٣ודhɖǼٕ׏ח׎׏אƏȇƳnǣɮƺȸÁɖȅȒȸ(ƺɮƺǼȒȵȅƺȇɎǣȇxǣƬƺِJƏɀɎȸȒƺȇɎƺȸȒǼȒǕɵِ ِבxƏȸ׏ח׎׏א0ȵɖƫِה׎׏ِב׎ِח׎׏אǴِǕƏɀɎȸȒِٖבד׏׎ِ׏׎

4. Schubert M, Colomé-Tatché M, Foijer F. (2019) Gene networks in cancer are biased by aneuploidies and sample impurities. Biochim Biophys Acta Gene Regul Mech. 2019 Oct 22:194444. doi: 10.1016/j.bbagrm.2019.194444.

,van den Bos H, Bakker B, Taudt A, Guryev V, Colomé-Tatché M, Lansdorp PM, Foijer F ِד ٣ªɖƏȇɎǣˡƬƏɎǣȒȇȒǔȇƺɖȵǼȒǣƳɵǣȇxƏȅȅƏǼǣƏȇ³ɵɀɎƺȅɀِ Methodsח׎׏א٢ِד³ȵǣƺȸǣȇǕɀ(!h ِד׏ٗוٮ׏בחזٮחבחגٮ׏ٮזוחٖו׏׎ِ׏׎׎ي׎ِƳȒǣח׏ٮחד׏يהחז׏ٕח׎׏אxȒǼ ǣȒǼِ

³ƬǝȒȒȇƺȇ¨xًkȒǸç¨ًáǣƺȸƺȇǕƏ0ً ƏǸǸƺȸ ًFoijer Fً³ȵǣƺȸǣȇǕɀ(!hًɮƏȇàɖǕɎxÁxِ .6 (2019) Premature mitotic entry induced by ATR inhibition potentiates olaparib inhibition- ٮא!» ȅƺƳǣƏɎƺƳǕƺȇȒȅǣƬǣȇɀɎƏƫǣǼǣɎɵًǣȇˢƏȅȅƏɎȒȸɵɀǣǕȇƏǼǣȇǕًƏȇƳƬɵɎȒɎȒɴǣƬǣɎɵǣȇ ِבודא׏ِ׏הא׎ٮזוז׏ٖא׏׎ِ׏׎׎ي׎ِƳȒǣגגאٮאאגאي٢׏׏٣בzȒɮٕ׏ח׎׏אȇƬȒǼِ ƳƺˡƬǣƺȇɎƬƏȇƬƺȸƬƺǼǼɀِxȒǼ Epub 2019 Oct 21.

7. Hong C, Tijhuis AE, Foijer F. (2019) The cGAS Paradox: Contrasting Roles for cGAS-STING Pathway in Chromosomal Instability. Cells. 2019 Oct 10;8(10). pii: E1228. doi: 10.3390/ cells8101228. Review.

8. Preprint: «ƺȵǼǣƬƏɎǣȒȇ³ɎȸƺɀɀJƺȇƺȸƏɎƺɀxɖǼɎǣȵǼƺ(ǣɀɎǣȇƬɎ!ǼƏɀɀƺɀȒǔ!Ȓȵɵzɖȅƫƺȸ AlterationzƏƳƺƺȅ³ǝƏǣǸǝًǼǣƬƺxƏɿɿƏǕƏɎɎǣً ǴȒȸȇ ƏǸǸƺȸً(ǣƏȇƏ!ƏȸȒǼǣȇƏhȒǝƏȇȇƏ ³ȵǣƺȸǣȇǕɀً«ƺȇƻáƏȸƳƺȇƏƏȸً(ƏȇǣƺǼxɖǼǣƏƳǣɎƏȇً0ǼƺȇǣxƏȇǣƏɎǣً¨ƺɎɎƺȸnƏȸɀɀȒȇًhɖȇáƏȇǕً זדהבגוƳȒǣِȒȸǕٖ׏׎ِ׏׏׎׏ٖٖٖيǝɎɎȵɀيƳȒǣٕזדהבגוIǼȒȸǣɀIȒǣǴƺȸً³ƏȸƏǝ0ǼǣɿƏƫƺɎǝxƬ!ǼƺǼǼƏȇƳƫǣȒ«ɴǣɮ

9. Preprint: ³ǣȇǕǼƺƬƺǼǼ(zɀƺȷɖƺȇƬǣȇǕȸƺɮƺƏǼɀƳǣɀɎǣȇƬɎȅȒǼƺƬɖǼƏȸɎɵȵƺɀȒǔƫƏɀƏǼƬƺǼǼ carcinoma with unique transcriptome features ǴȒȸȇ ƏǸǸƺȸًhȒȸȸǣɎÁƺȸȸƏًnǣȇñǝȒɖً Emoke Racz, Sonja Paljic, Jorge Garcia-Martinez, Vera Oliveira, Petra L Bakker, ƳȒǣِٖٖيǝɎɎȵɀيƳȒǣٕחח׏אחגǣƏȇƏ!ِhِ³ȵǣƺȸǣȇǕɀًxƏȸƬƺǼIِhȒȇǸȅƏȇًIǼȒȸǣɀIȒǣǴƺȸƫǣȒ«ɴǣɮ) org/10.1101/492199

10. Preprint: Altering microtubule dynamics is synergistically toxic with inhibition of the ǝǣǝnǣȇًxǣƬǝƏƺǼ³ƬǝɖƫƺȸɎً³ɎƺȵǝƏȇǣƺIِ!ٮspindle checkpointkǼƏɀǸƺxِ³ƬǝɖǸǸƺȇًçǣ ȸƺɖɀɀًhɖƳǣɎǝ0ِ³ǣȅȒȇًRǣǼƳƏɮƏȇƳƺȇ ȒɀًñɖɿƏȇƏ³ɎȒȸƬǝȒɮƏًxƏȸǣƏ!ȒǼȒȅƺÁƏɎƬǝƺً¨ ƳȒǣِٖٖيǝɎɎȵɀيƳȒǣٕוו׎ה׎וRȒǼǕƺȸ ƏɀɎǣƏȇɀً(ǣƏȇƏ!ِhِ³ȵǣƺȸǣȇǕɀًIǼȒȸǣɀIȒǣǴƺȸƫǣȒ«ɴǣɮ org/10.1101/706077

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ERIBA | Annual Report V2.indd 25 16-07-2020 21:00 Laboratory of Ageing Biology and Stem Cells Group Leader: Gerald de Haan

1. Buisman SC, de Haan G.(2019) Epigenetic Changes as a Target in Aging Haematopoietic Stem Cells and Age-Related Malignancies. Cells. 2019 Aug 10;8(8). pii: E868. doi: 10.3390/ cells8080868.

ƬǸƺȸȅƏȇȇÁًRƏȸɎǼƺƫƺȇJًxɜǼǼƺȸ!ًxƏɀɎȸȒƫɖȒȇǣJًJȸȒɎǝxً³ɎƺȸǸƺȇ ًñƏǣȇǣxً .2 çȒɖɀɀƺǔ³ًñɖǣƳǝȒǔR«ًkȸƏɖɀɀ³«ًkȒȸɎȅƏȇJًde Haan GًƳƺ ȸɖǣȇًáƏȇǕñª ٣C/EBPɴ-LIP induces cancer-type metabolicח׎׏אǼƏɎɿƺȸxًkƺȅȵƏ³ً!ƏǼǸǝȒɮƺȇ!Iِ٢¨ reprogramming by regulating the let-7/LIN28B circuit in mice. Commun Biol. 2019 Jun 14;2:208. doi: 10.1038/s42003-019-0461-z. eCollection 2019.

áȒǴɎȒɯǣƬɿ00ً ȸȒƺǸǝɖǣɀxh!ًáƺƺȸɀǣȇǕ0ً(ǣȇǣɎɿƺȇًàƺȸȒɮɀǸƏɵƏ0ًɖɀƺȅƏً«ǣɎɀƺȅƏ .3 ȸƺȇƺɯƏǼًǼǣǔƺɀȵƏȇًƏȇƳٮƏƺȇǝƏȇƬƺɀɀƺǼǔדא׏ٮ»xًñɯƏȸɎ0ًde Haan G, Bystrykh LV.(2019) xǣ migration of murine hematopoietic stem and progenitor cell clones. Sci Rep. 2019 Mar ɿِٮב׎דזבٮח׎׏ٮזחד׏גɀٖזב׏׎ِ׏׎يƳȒǣِדזוגي٢׏٣חٕז׏

ً»ɖɀƺȅƏًñɯƏȸɎ0ً³ƬǝƺȵƺȸɀRً(ƺǸǸƺȸxٮhɖȇǕhً ɖǣɀȅƏȇ³!ًáƺƺȸɀǣȇǕ0ً(ƺɎǝȅƺȸɀ .4 nƏɿƏȸƺ³³ًRƏȅȅƺȸǼIً³ǸȒǸȒɮƏçًkȒȒǣɀɎȸƏ³xًkǼƏɖǸƺkً¨ȒȒɎ«ً ɵɀɎȸɵǸǝnàًde Haan G (2019) CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions. Cell Rep. 2019 ׎ِד׎׏ِ׎ِח׎׏אǴِƬƺǼȸƺȵِٖה׏׎ِ׏׎׏يƳȒǣِזƺِז׏ח׏ٮה׎ח׏ي٣ו٢האٕאIƺƫ׏

ƺǼƳƺȸƫȒɀx0׏ًhƏƬȒƫɀ³ًkȒɀɎƺȸÁkًɖɀƺȅƏًáƺƺȸɀǣȇǕ0ًñɯƏȸɎ0ًde Haan G, Bystrykh ِד ȒȇȒȸRƺɎƺȸȒǕƺȇƺǣɎɵǣȇɎǝƺ!ǼȒȇƏǼ(ɵȇƏȅǣƬɀȒǔÁȸƏȇɀȵǼƏȇɎƺƳ)ٮɎȒٮLV.(2019) (ȒȇȒȸ Human Cord Blood Stem Cells in Murine Xenografts. Biol Blood Marrow Transplant. 2019 ِהא׎ِז׎ِח׎׏אǴِƫƫȅɎِٖה׏׎ِ׏׎׏يæِƳȒǣٮההד׎ב٣ח׏٢׏חוזٮבז³׏׎يȵǣǣِד³ƺȵ

Laboratory of Macromolecules and Interactomes Group Leader: John LaCava

ً¨ǕǝƫƏǣƺًÁƏɵǼȒȸx³ًRɖɀƫƏȇƳ(ً(ƺɀǝȵƏȇƳƺàً³ɎƺȸƏȇǸƏh ȸƳƺǼǴƏȇ(ًáƏȇǕæً .1 JȒȸƫȒɖȇȒɮxًçƏȇǕá«ً³ǣƺ ًnƏȸȅƏȇR ًhǣƏȇǕRًxȒǼǼȒɵk«ًǼɎɖǸǝȒɮXًnǣñً xƬkƺȸȸȒɯáًIƺȇɵȜ(ً ɖȸȇɀkRًLaCava J. (2019)LINE-1 ORF2p expression is nearly דאגגגוƳȒǣِȒȸǕٖ׏׎ِ׏׏׎׏ٖٖٖيǝɎɎȵɀيimperceptible in human cancers.ƳȒǣ

ً!Carter V, LaCava JًÁƏɵǼȒȸx³ًnǣƏȇǕ³çًxɖɀɎƺǼǣȇ!ًÈǸƏƳǣǸƺk!ً ƺȇǕɎɀɀȒȇًnȒȒƳ .2 ׎גMustelin T(2019) RǣǕǝ¨ȸƺɮƏǼƺȇƬƺƏȇƳ(ǣɀƺƏɀƺ!ȒȸȸƺǼƏɎǣȒȇȒǔɖɎȒƏȇɎǣƫȒƳǣƺɀǕƏǣȇɀɎȵ Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus. ِגד׏׎גƏȸɎِٖא׏׎ِ׏׎׎يƳȒǣِחחٮחזي٢׏٣או׎hƏȇٕא׎אȸɎǝȸǣɎǣɀ«ǝƺɖȅƏɎȒǼِ

áǣȇƬɿɖȸƏkً(ȒȅƏȇɀǸǣxً LaCava J (2019) ǔˡȇǣɎɵ¨ȸȒɎƺȒȅǣƬȇƏǼɵɀǣɀȒǔɎǝƺRɖȅƏȇ .3 يƳȒǣِדאבٮ׏חאيאה׎א׎ٕא׎אExosome and Its Cofactor Complexes.xƺɎǝȒƳɀxȒǼ ǣȒǼِ ِד׏ٗוٮאאזחٮחבחגٮ׏ٮזוחٖו׏׎ِ׏׎׎

ǕǝƫƏǣƺxً·ɖǼƬ¨ًIƺȇɵȜ(ً¨ƺȇȇȒƬǸxً LaCava J (2019) Complex+: Aided Preprint: .4 הדהגגוƳȒǣِȒȸǕٖ׏׎ِ׏׏׎׏ٖٖٖيǝɎɎȵɀيxƏǸǣȇǕǔȒȸɎǝƺ³ɎɖƳɵȒǔ¨ȸȒɎƺǣȇ!ȒȅȵǼƺɴƺɀِƳȒǣٮƺƬǣɀǣȒȇ)

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ERIBA | Annual Report V2.indd 26 16-07-2020 21:00 Laboratory of Cellular Biochemistry Group Leader: Liesbeth Veenhoff

1. Mishra A, Sipma W, Veenhoff LM, Van der Giessen E, Onck PR. (2019) The Effect of FG-Nup Phosphorylation on NPC Selectivity: A One-Bead-Per-Amino-Acid Molecular ِהחד׎ב׎׎א׎ٖǣǴȅɀחבב׏׎ِيƳȒǣِהחד0ي٣ِȵǣǣב׎٢א׎ٕבhƏȇח׎׏אɵȇƏȅǣƬɀ³ɎɖƳɵِXȇɎhxȒǼ³Ƭǣِ)

ƺȅȵƺǼXnً!ȸƏȇƺxxًÁǝƏǼǼƺȸ(hًxǣɀǝȸƏًhƏȇɀƺȇ(¨ًhƏȇɀɀƺȇɀJً¨ȒȵǸƺȇ¨ًǸɆǣɎً» .2 -ȇƬǸ¨«ًnɖɀǸ!¨ًVeenhoff LM.(2019) Age kƏƺƫƺȸǼƺǣȇxًɮƏȇƳƺȸJǣƺɀɀƺȇ0ً³Ɏƺƺȇً dependent deterioration of nuclear pore assembly in mitotic cells decreases transport نِהז׏זגƺnǣǔƺِٖגדדו׏׎ِيƳȒǣِהז׏זגƺيȵǣǣِזٕבhɖȇח׎׏אdynamics.0Ǽǣǔƺِ

ƺȸǼƺz!ًkƏɿƺȅǣƺȸRJًVeenhoff zȒɮƏȸǣȇƏ(ًhƏȇɀɀƺȇɀJ0ً ȒǸƺȸȇkً³ƬǝɖɎÁًɮƏȇ .3 ɯǣƳƺɀƬȸƺƺȇǣƳƺȇɎǣˡƺɀǕƺȇƺɀɎǝƏɎɀɖȵȵȸƺɀɀٮLM,Chang M. Ageing Cell (2019) ǕƺȇȒȅƺ ,Aging Cell نɎǝƺƏƬƬɖȅɖǼƏɎǣȒȇȒǔɀȵȒȇɎƏȇƺȒɖɀȅɖɎƏɎǣȒȇɀǣȇɵȒɖȇǕƏȇƳƏǕƺƳɵƺƏɀɎƬƺǼǼɀِ וזדאחגƳȒǣِȒȸǕٖ׏׎ِ׏׏׎׏ٖٖٖي١ِǝɎɎȵɀגז׎ב٣ً٠ƺ׏א٢ח׏

4. I.L. Rempel, P. Popken, A. Ghavami, A. Mishra, R.A.Hapsari, A.H.G. Wolters, A.C. Veldsink, .ȇƬǸًِ³ɎƺƺȇًL. M xِkǼƏƏɀɀƺȇɀًِ!ِxƺǣȇƺȅƏً ِ¨ȒȒǼȅƏȇً ِzِJِJǣƺȵȅƏȇɀً¨ِ«ِ Veenhoff. Structure (2019) IǼƺɴǣƫǼƺǣƏȇƳƺɴɎƺȇƳƺƳǼǣȇǸƺȸƳȒȅƏǣȇɀɀɖȵȵȒȸɎƺǔˡƬǣƺȇɎ Ǵِٖה׏׎ِ׏׎׏يX )אדבה׎ז׏בي)xX¨نɎȒɎǝƺǣȇȇƺȸȇɖƬǼƺƏȸȅƺȅƫȸƏȇƺِאɎƏȸǕƺɎǣȇǕȒǔRƺǝ str.2019.11.003

I.L. Rempel, A. Steen, L.M. Veenhoff. Poor old pores – The challenge of making and ِד يX )א׏וגד׏ו!x¨ي)x!X¨نmaintaining nuclear pore complexes in aging.I0 ³h ד׎אד׏׎ِ׏׏׏׏ٖǔƺƫɀِ׏

6. Preprint: A physicochemical roadmap of yeast replicative aging Sara N. Mouton, ِ!ƏɮǣƳhِÁǝƏǼǼƺȸًxƏɎɎǝƺɯxِ!ȸƏȇƺًXȸǣȇƏnِ«ƺȅȵƺǼًȇɎȒȇ³ɎƺƺȇًxƏɎɎkƏƺƫƺȸǼƺǣȇً) ƳȒǣِٖٖيǝɎɎȵɀي׎ٕƳȒǣאוזדזPatrick Lusk, Arnold J. Boersma, Liesbeth M. Veenhoff.ƫǣȒ«ɴǣɮ ׎אוזדזȒȸǕٖ׏׎ِ׏׏׎׏ٖ

Laboratory of Cellular Senescence and Age-related Pathologies xƏȸƬȒ(ƺȅƏȸǣƏيJȸȒɖȵnƺƏƳƺȸ

1. Soto-Gamez A, Quax WJ, (ƺȅƏȸǣƏx (2019) Regulation of Survival Networks in Senescent يƳȒǣِבגהאٮחאהאي٣ד׏٢׏בגٕאhɖǼ׏ח׎׏אCells: From Mechanisms to Interventions.hxȒǼ ǣȒǼِ ׏ِבxƏɵח׎׏א0ȵɖƫِהב׎ِד׎ِח׎׏אǴِǴȅƫِٖה׏׎ِ׏׎׏

ƏǼȅƺȸkًæɖxًñǝɖçً¨ǣȸɎɀǸǝƏǼƏɮƏÁًáƺǣɮȒƳƏxxًRƏƬǝǔƺǼƳ!xً¨ȸƏɎƏnJًɮƏȇ(ǣǴǸ¨ .2 ǕȸȒƳȇǣǸ ً!ɖƫȸȒRً(ȒȒȸȇƺƫƏǼ0hً àƺȸɿȒɀƏJًhȒǝȇɀȒȇkٮÁRًàƺȸǸƏƳƺ0ً!ƏɀƏƬǼƏȇǕ xًhɖȸǸ(ًhƺȇɀƺȇx(ً!ǝǣȇǣ0zًxǣǼǼƺȸh(ًxƏɎɮƺɵƺȇǸȒً³ɎȒɖɎx ً³ƬǝƏǔƺȸxhًáǝǣɎƺ TA, Hickson LJ, (ƺȅƏȸǣƏxًJƏȸȒɮǣƬàًJȸƏȇƳƺhًȸȸǣƏǕƏ0ًkɖǣȵƺȸɀIًɮȒȇñǕǼǣȇǣƬǸǣ ٣Targeting senescent cellsח׎׏אÁًnƺ ȸƏɀɀƺɖȸzkً!ƏȅȵǣɀǣhًÁƬǝǸȒȇǣƏÁًkǣȸǸǼƏȇƳhnِ٢ ي׎ِƳȒǣדחאƺ׏ي٣ב٢זhɖȇٕ׏ח׎׏אalleviates obesity-induced metabolic dysfunction.ǕǣȇǕ!ƺǼǼِ ِדאxƏȸח׎׏א׎ِ0ȵɖƫדחא׏׎ِ׏׏׏׏ٖƏƬƺǼِ׏

ٮƏǼƏƬǣȒnًJȒɵƺȸxnًxƏǕǕǣȒȸƏȇǣ(ً0ɀȵǣȇȒɀƏًàǣǼǼƺȇƺɖɮƺzً ȒɖȸƫȒȇȇƏǣɀ³ًxȒȷɖǣȇ¨ .3 Restored ٣ח׎׏א٢!Beaudry G, Le O, (ƺȅƏȸǣƏxً(ƏɮƏǼȒɀ«ً(ƺƬƏǼɖɯƺRً ƺƏɖɀƻǴȒɖȸ immune cell functions upon clearance of senescence in the irradiated splenic environment Aging Cell. 2019 Aug;18(4):e12971. doi: 10.1111/acel.12971. Epub 2019 May 31.

ٮHernandez-Segura A, Rubingh R, (ƺȅƏȸǣƏx (2019) XƳƺȇɎǣˡƬƏɎǣȒȇȒǔɀɎƏƫǼƺɀƺȇƺɀƬƺȇƬƺ .4 associated reference genes. Aging Cell. 2019 Apr;18(2):e12911. doi: 10.1111/acel.12911. Epub 2019 Feb 1

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ERIBA | Annual Report V2.indd 27 16-07-2020 21:00 :ƏǼƬǣȇȒɎɎȒًkȒǝǼǣhًñƏǕƏɎȒ0ً¨ƺǼǼƺǕȸǣȇǣnً (ƺȅƏȸǣƏx, Alimonti A. Cellular Senescence! ِד ٖאד׏׎ِ׏׏يƳȒǣِזו׏׎ٮוג׏׎ي٣א٢חחȵȸ׏ٕח׎׏אAging, Cancer, and Injury. ¨ǝɵɀǣȒǼ«ƺɮِ physrev.00020.2018.

,áǣǼƺɵ!(ًnǣɖ³ًnǣȅƫƏƳ!ًñƏɯƏƳɿǸƏxً ƺƬǸhً(ƺȅƏȸǣƏx, Artwood R, Alimirah F .6 ً»ȸȒȇÁ ȒȅǣȇǕɖƺɿhًkɖƺǝȇƺȅƏȇȇ!ً(ƏȇǣƺǼɀȒȇ³«ً ƏɀǣɀɎɵzًkƏɀǼƺȸRJً)ٮnȒȵƺɿ !٣³Xnח׎׏א٢ِ¨ƺɀȵȸƺɿ¨çًxȒȒȇƺɵ³(ًJǣƫɀȒȇ áً³ƬǝǣǼǼǣȇǕ ً!ƏȅȵǣɀǣhًkƏȵƏǝǣ) Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells. ِחג׎ِז׎ِח׎׏אǴِƬƺǼȸƺȵِٖה׏׎ِ׏׎׏يƳȒǣِדƺِובבבٮחאבבي٣ב٢׏זאٕגא³ƺȵח׎׏אƺǼǼ«ƺȵِ!

ً ǣɀǝȒȵ!ً!Əȅȵǣɀǣhً!ȒǼǼƏƳȒ JȒȸǕȒɖǼǣɀàًƳƏȅɀ¨(ًǼǣȅȒȇɎǣً ƺȇȇƺɎɎ(!ً ǣɀƬǝȒǔ .7 xً0ɮƏȇǕƺǼȒɖkًIƺȸƫƺɵȸƺJًJǣǼhًRƏȸƏ0ًkȸǣɿǝƏȇȒɮɀǸɵàًhɖȸǸ(ًxƏǣƺȸ ًzƏȸǣɎƏxً zǣƺƳƺȸȇǝȒǔƺȸnً¨ƏɀɀȒɀhIً«Ȓƫƫǣȇɀ¨(ً³ƬǝȅǣɎɎ!ً³ƺƳǣɮɵhًàȒɖǕƏɀkًɮȒȇñǕǼǣȇǣƬǸǣÁً ƺˡȇǣȇǕƏ¨ƏɎǝIȒȸɯƏȸƳِ)يñǝȒɖ(ً³ƺȸȸƏȇȒxً (ƺȅƏȸǣƏxِ (2019) !ƺǼǼɖǼƏȸ³ƺȇƺɀƬƺȇƬƺ ِד׏׎ِ׎׎ِח׎׏אǴِƬƺǼǼِٖה׏׎ِ׏׎׏يƳȒǣِואזٮב׏זي٣ג٢חו׏ٕ׏בƬɎ ח׎׏אƺǼǼِ!

ƏɎǣǼ¨ً(ȒȇǕªًáƏȇǕ(ً!ǝƏȇǕhًáǣǼƺɵ!ً(ƺȅƏȸǣƏxًnƺƺhًkƏȇǕhًzǣƺƳƺȸȇǝȒǔƺȸnً¨ .8 ٮƏגXzkה٣³ɵɀɎƺȅǣƬƬǼƺƏȸƏȇƬƺȒǔ¨׏ח׎׏א٢ِח׎׏אȒƫƫǣȇɀ¨ً³ȒɯƏJً!ƏȅȵǣɀǣhًñǝȒɖ(ًàȒzِ» positive senescent cells mitigates age-associated intervertebral disc degeneration. Aging Cell. 3:e12927

Laboratory of and Genome Integrity Group Leader: Michael Chang

ƺȸǼƺz!ًkƏɿƺȅǣƺȸRJًàƺƺȇǝȒǔǔ zȒɮƏȸǣȇƏ(ًhƏȇɀɀƺȇɀJ0ً ȒǸƺȸȇkً³ƬǝɖɎÁًɮƏȇ .1 ɯǣƳƺɀƬȸƺƺȇǣƳƺȇɎǣˡƺɀǕƺȇƺɀɎǝƏɎɀɖȵȵȸƺɀɀɎǝƺٮLM,Chang M (2019) ǕƺȇȒȅƺ نaccumulation of spontaneous mutations in young and aged yeast cells.ǕƺǣȇǕƬƺǼǼ וזדאחגƳȒǣِȒȸǕٖ׏׎ِ׏׏׎׏ٖٖٖي١ِǝɎɎȵɀגז׎ב٣ً٠ƺ׏א٢ח׏

Laboratory of Genetic Instability and Ageing Group Leader: Peter Lansdorp

ȒǼǝƏȷɖƺǣȸȒ!Iً¨ȒȇɀǣȒƺȇ ً ƏǸǸƺȸ ًkǼƏƏɀƺȇ³hًkɖƬɖǸǸȒɀƺ0ًɮƏȇhƏƏȸɀɮƺǼƳ«Rًàǣɮǣƻ .1 kǼǣȇǸXًRƏȅǣzً³ȵǣƺȸǣȇǕɀ(!hً³ƏɀƏǸǣzً(ɖɎɎƏ(ً ȒǴ³Iًàȸǣƺɀ«JhًLansdorpٮhًàƺȸǼƏƏȇ ًIȒǣǴƺȸIً³ȇǣȵȵƺȸɎ ɖƳƺȇƏƏȸƳƺȇً!ǼƺɮƺȸɀRًkȸƏȇƺȇƫɖȸǕ PMًɮƏȇƳƺáƺɎƺȸǣȇǕxًɮƏȇ ٣Ongoing chromosomal instability and karyotype evolution inח׎׏אRhJًkȒȵɀJh¨n٢ ٖזב׏׎ِ׏׎يƳȒǣِגבזٮגאזي٣ד׏٢דxƏɵٕח׎׏אhuman colorectal cancer organoids.zƏɎJƺȇƺɎِ ِחאȵȸח׎׏א0ȵɖƫِהٮחחב׎ٮח׎׏ٮזזד׏גɀ

ǝƏǣɀɀȒȇxh¨ً³ƏȇƳƺȸɀ(ًñǝƏȒæًxƏǼǝȒɎȸƏً¨ȒȸɖƫɀǸɵ(ً«ƏɖɀƬǝÁًJƏȸƳȇƺȸ0hً! .2 nًJɖȒnً!ȒǼǼǣȇɀ«nًIƏȇæًáƺȇhًRƏȇƳɀƏǸƺȸ«0ًIƏǣȸǼƺɵ³ًkȸȒȇƺȇƫƺȸǕ ȒƳȸǣǕɖƺɿ» ñzًkȒȇǕæًRȒȸȅȒɿƳǣƏȸǣIًnƺƺ(ًáƺȇǕƺȸxًRƏɀɎǣƺ«ًȇɎƏǸǣ(ًȇƏȇɎǝƏȸƏȅƏȇÁً Audano PA, Brand H, Cantsilieris S, Cao H, Cerveira E, Chen C, Chen X, Chin CS, Chong ñً!ǝɖƏȇǕzÁًnƏȅƫƺȸɎ!!ً!ǝɖȸƬǝ(xً!ǼƏȸǸƺnًIƏȸȸƺǼǼًIǼȒȸƺɀhًJƏǼƺƺɮÁًJȒȸǸǣȇ(Èً nƺƺh0ًnƺƺhًnƺƺًואJɖǴȸƏǼxًJɖȸɵƺɮàًRƺƏɎȒȇáRًkȒȸǼƏƬǝhًkɖȅƏȸ³ًkɯȒȇhçًnƏȅ0Á xƏȸɎǣȇƺɿkًxƺǣƺȸɀ³ًxɖȇɀȒȇkxًzƏɮƏȸȸȒI!¨ًzƺǼɀȒȇٮá¨ًnƺƺ³¨ًnǣ³ًxƏȸǸɀ¨ًàǣƏɖƳ ƏȇƏǕǣȒɎȒȵȒɖǼȒɖ³ً¨ƏȇǕá!ًªǣɖçً«ȒɀƏȇǣȒJً¨ٮhًzȒƳɿƏǸ!ًzȒȒȸًkɵȸǣƏɿȒȵȒɖǼȒɖ ٮɵƏȇxً³ɎɜɎɿً³ȵǣƺȸǣȇǕɀ(!hًáƏȸƳًáƺǼƬǝ0ًæǣƏȒxًæɖáًñǝƏȇǕ!ًñǝɖªًñǝƺȇǕ» ȸƏƳǼƺɵæًnȒɯɵ0ًçƏǸȇƺƺȇ³ًxƬ!ƏȸȸȒǼǼ³ًhɖȇJً(ǣȇǕnًkȒǝ!nً«ƺȇ ًIǼǣƬƺǸ¨ً!ǝƺȇ kًJƺȸɀɎƺǣȇx ًkɯȒǸ¨çًLansdorp PMًxƏȸɎǝJÁً³ƺƫƏɎhً³ǝǣæً Əɀǝǣȸًçƺkً(ƺɮǣȇƺ Multi-platform ٣ח׎׏א٢ِ!0ǣƬǝǼƺȸ00ًnƺƺ ³0ًÁƏǼǸȒɯɀǸǣx0ًxǣǼǼɀ«0ًxƏȸɀƬǝƏǼǼÁًkȒȸƫƺǼh discovery of haplotype-resolved structural variation in human genomes. Nat Commun. نɿٮזג׏ז׎ٮז׎׏ٮוהג׏גɀٖזב׏׎ِ׏׎يƳȒǣِגזו׏ي׏׎٢׏٣ٕהȵȸ׏ח׎׏א

3. van den Bos H, Bakker B, Taudt A, Guryev V, Colomé-Tatché M, Lansdorp PM , Foijer F, ٣ªɖƏȇɎǣˡƬƏɎǣȒȇȒǔȇƺɖȵǼȒǣƳɵǣȇxƏȅȅƏǼǣƏȇ³ɵɀɎƺȅɀِ Methods Molח׎׏א³ȵǣƺȸǣȇǕɀ(!h٢ ِד׏ٗוٮ׏בחזٮחבחגٮ׏ٮזוחٖו׏׎ِ׏׎׎ي׎ِƳȒǣח׏ٮחד׏يהחז׏ٕח׎׏אǣȒǼِ

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ERIBA | Annual Report V2.indd 28 16-07-2020 21:00 (ÁƏɎƬǝƻxًLansdorp PM, Guryev V. (2019ٮȒȸɖƫɀǸɵ(ً³ƏȇƳƺȸɀ(ًÁƏɖƳɎً!ȒǼȒȅƻ¨ .4 breakpointR: an R/Bioconductor package to localize strand state changes in Strand-seq data. Bioinformatics. 2019 Aug 30. pii: btz681. doi: 10.1093/bioinformatics/btz681.

ÁƏȅȅǣȇǕƏxًƳƺáǣɎ³ًàƏȇ(ƺáƏɖɯƺȸ!ًɮƏȇƳƺȇ ȒɀRً³ɯƺȇȇƺȇǝɖǣɀhIًkǼǣȇǸƺȇƫƺȸǕ ِד ÁhًRǣǼɎƺȸȅƏȇȇÁhzًȇƳȸƺƺk!ً³ȵǣƺȸǣȇǕɀ(!hًLansdorp PM, van den Berg A, Timens W, Terstappen LW, Groen HJ. Release of circulating tumor cells during surgery for non-small cell lung cancer: are they what they appear to be? Clin Cancer Res. 2019 Nov ׏ِ٠0ȵɖƫƏǝƺƏƳȒǔȵȸǣȇɎ١גדאٮח׏ٮ»!!ِאבג׎ٮזו׏׎ٖזד׏׎ِ׏׏يƳȒǣِח׎׏א׏ِגדאƬǼǣȇƬƏȇȸƺɀِيȵǣǣِהא ِאא׏אוו׏בي)ɖƫxƺƳ¨xX¨

àȒǼǼǕƺȸx«ًnȒǕɀƳȒȇJًɖƳƏȇȒ¨ً³ɖǼȒɮƏȸǣً¨ȒȸɖƫɀǸɵ(ً¨ƺǼɖɀȒ¨ًáƺȇǕƺȸxً .6 ȒȇƬƺȵƬǣȒȇJÁًkȸȒȇƺȇƫƺȸǕñzًxɖȇɀȒȇkxً ƏǸƺȸ!ً³ƏȇƳƺȸɀ(ً³ȵǣƺȸǣȇǕɀ(!hً! Lansdorp PM, Surti U, Hunkapiller MW, Eichler EE. (2019) Improved assembly and variant ˡƳƺǼǣɎɵǼȒȇǕȸƺƏƳɀِٮȅȒǼƺƬɖǼƺًǝǣǕǝٮƳƺɎƺƬɎǣȒȇȒǔƏǝƏȵǼȒǣƳǝɖȅƏȇǕƺȇȒȅƺɖɀǣȇǕɀǣȇǕǼƺ Ann Hum Genet. 2019 Nov 11. doi: 10.1111/ahg.12364. [Epub ahead of print]

7. Pillay N, Tighe A, Nelson L, Littler S, Coulson-Gilmer C, Bah N, Golder A, Bakker B, ǕǣǼɮǣƺ(hًIȒǣǴƺȸIً ³ȵǣƺȸǣȇǕɀ(!hًhƏȅƺɀ(Xً³ȅǣɎǝkxًhȒȸƳƏȇxًxȒȸǕƏȇ«(ً ɮƏȸǣƏȇ!ƏȇƬƺȸ z«ƺȵǼǣƬƏɎǣȒȇàɖǼȇƺȸƏƫǣǼǣɎǣƺɀ«ƺȇƳƺȸ)٣ח׎׏אhƏƬǸɀȒȇ(ًÁƏɵǼȒȸ³³ِ٢ ǣƫȒɀƺ٣JǼɵƬȒǝɵƳȸȒǼƏɀƺXȇǝǣƫǣɎȒȸɀِ Cancer Cell. 2019 Mar»ٮ¨)ƺǼǼɀ³ƺȇɀǣɎǣɮƺɎȒ¨ȒǼɵ٢! ِג׎׎ِא׎ِח׎׏אǴِƬƬƺǼǼِٖה׏׎ِ׏׎׏يƳȒǣِזƺِבבדٮח׏דي٣ב٢דבٕז׏

8. Lansdorp P, van Wietmarschen N. Helicases FANCJ, RTEL1 and BLM Act on Guanine /ªɖƏƳȸɖȵǼƺɴ(zǣȇàǣɮȒِ Genes (Basel). 2019 Oct 31;10(11). pii: E870. doi: 10.3390 ِדודבזה׏בي)׎ِ«ƺɮǣƺɯِ¨ɖƫxƺƳ¨xXוזǕƺȇƺɀ׏׎׏׏׎

³ɖǼȒɮƏȸǣًnǣ«ًɖƳƏȇȒ¨ً¨ȒȸɖƫɀǸɵ(ًàȒǼǼǕƺȸx«ًnȒǕɀƳȒȇJٕRɖȅƏȇJƺȇȒȅƺ .9 Structural Variation Consortium, Warren WC, Pollen AA, Chaisson MJP, Eichler EE. ɀȵƺƬǣˡƬɎƏȇƳƺȅȸƺȵƺƏɎƺɴȵƏȇɀǣȒȇƏȇƳƳǣǔǔƺȸƺȇɎǣƏǼǕƺȇƺƺɴȵȸƺɀɀǣȒȇƳɖȸǣȇǕٮRɖȅƏȇ ٖבו׏׎ِ׏׎يƳȒǣِבדאבאٮבגאבאي٣הג٢ה׏׏ٕאzȒɮ׏ח׎׏אprimate evolution.¨ȸȒƬzƏɎǼƬƏƳ³Ƭǣȳِ ي)ɖƫxƺƳ!ƺȇɎȸƏǼ¨x!X¨ٕוא׎חדה׏בي)ɖƫxƺƳ¨xX¨ِזאƬɎ ח׎׏א0ȵɖƫِה׏׏דו׏א׏חȵȇƏɀِ׏ זהבחדזה!x¨

³ƬǝȒȒȇƺȇ¨xًkȒǸç¨ًáǣƺȸƺȇǕƏ0ً ƏǸǸƺȸ ًIȒǣǴƺȸIً³ȵǣƺȸǣȇǕɀ(!hًɮƏȇàɖǕɎxÁxِ .10 Premature mitotic entry induced by ATR inhibition potentiates olaparib inhibition- ٮא!» ȅƺƳǣƏɎƺƳǕƺȇȒȅǣƬǣȇɀɎƏƫǣǼǣɎɵًǣȇˢƏȅȅƏɎȒȸɵɀǣǕȇƏǼǣȇǕًƏȇƳƬɵɎȒɎȒɴǣƬǣɎɵǣȇ ِבודא׏ِ׏הא׎ٮזוז׏ٖא׏׎ِ׏׎׎ي׎ِƳȒǣגגאٮאאגאي٢׏׏٣בzȒɮٕ׏ח׎׏אȇƬȒǼِ ƳƺˡƬǣƺȇɎƬƏȇƬƺȸƬƺǼǼɀِxȒǼ ׏ِדאאאזה!x¨ي)ɖƫxƺƳ!ƺȇɎȸƏǼ¨x!X¨ٕד׏החאד׏בي)׏ِ¨ɖƫxƺƳ¨xXאƬɎ ח׎׏א0ȵɖƫ

ɿǣɿkًnǣȅɿƺȸɯƏǼƏhIً³ɎɖȸȅǼƺƬǝȇƺȸXًRɖȸǼƺɵ0ًñǝƏȇǕ!ًhƺǕƏȇƏɎǝƏȇk ًzƺǼɀȒȇJً .11 ٔ ȸǣƺȇ(«ًkȒƬǝƺȸhًçȒɖɀɀƺǔ³ًɮƏȇ«ƺƺ ًɮƏȇ(ƺɖȸɀƺȇ0hً ȸȒȇǸ³ًIǣƺȸȸȒàƺǼƏɀƬȒ« hRًƳƺ ȸɖǣȇًɮƏȇƳƺȇ ȒɀRً³ȵǣƺȸǣȇǕɀ(!hًIȒǣǴƺȸIًɮƏȇƳƺ³Ǽɖǣɀ ً«ȒƫƺȸɎɀn«ًJȒȸƺɀ JhًnǣRًɮƏȇ(ƺɖȸɀƺȇhxِCcne1 Overexpression Causes Chromosome Instability in Liver ِאƺ׏ِהאאٮ׏׎אي٢׏٣ודhɖǼٕ׏ח׎׏אƺǼǼɀƏȇƳnǣɮƺȸÁɖȅȒȸ(ƺɮƺǼȒȵȅƺȇɎǣȇxǣƬƺِJƏɀɎȸȒƺȇɎƺȸȒǼȒǕɵِ! ɖƫxƺƳ¨ٕזהגזוז׎בي)ɖƫxƺƳ¨xX¨ِבxƏȸ׏ח׎׏א0ȵɖƫِה׎׏ِב׎ِח׎׏אǴِǕƏɀɎȸȒِٖבד׏׎ِ׏׎يƳȒǣ ِוז׎׎׏זה!x¨ي)ƺȇɎȸƏǼ¨x!X!

ɮƏȇJǣǴȇ³0ًáǣƺȸƺȇǕƏ0ًɮƏȇƳƺȇÁƺȅȵƺǼzًkȒǸç¨ًRƺǣǴǣȇǸxً³ȵǣƺȸǣȇǕɀ(!hًIȒǣǴƺȸ .12 F, van Vugt MATM, Fehrmann RSN. TPX2/Aurora kinase A signaling as a potential ٮאדזي٣ה٢זבIƺƫٕח׎׏אȇƬȒǕƺȇƺِ therapeutic target in genomically unstable cancer cells. ׎ٕ¨ɖƫxƺƳגזוו׎׏בي)ɖƫxƺƳ¨xX¨ِב³ƺȵז׎׏א0ȵɖƫِאٮ׎וג׎ٮז׎׏ٮזזב׏גɀٖזב׏׎ِ׏׎يƳȒǣِוהז ׏׏ِאוהבה!x¨ي)ƺȇɎȸƏǼ¨x!X!

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ERIBA | Annual Report V2.indd 29 16-07-2020 21:00 Laboratory of Genome Structure Ageing Group Leader: Victor Guryev

,xƏǝȅɖƳRًÁƺȸ0ǼɀɎً³ƬǝƺȸȵƺȇIhJً ȒƺȸÁxًkƏȅȵƺȇk«ًƳƺRƏƏɀàًGuryev V .1 ٣Peptide microarray ofח׎׏אƺȵȵƺǼƺȇƫȒɀƬǝxxًkȒȸȇƫǼƏɖ³xًƳƺ ȒȇɎ0³hxِ٢¨ ȵƺƳǣƏɎȸǣƬƏƬɖɎƺȅɵƺǼȒǣƳǼƺɖǸƺȅǣƏǣɀȸƺǼƏɎƺƳɎȒȸƺǼƏȵɀƺƏȇƳȸƺɮƺƏǼɀǣȇɮȒǼɮƺȅƺȇɎȒǔ(z ٖאבהז׏׎ِ׏ي׎ِƳȒǣחהגٮחוהגي٣דג׏׎٢ٕבאhɖǼח׎׏אȇƬȒɎƏȸǕƺɎِ damage response and repair. oncotarget.27086. eCollection 2019 Jul 23.

2. Boudewijn IM, Lan A, Faiz A, Cox CA, Brouwer S, Schokker S, Vroegop SJ, Nawijn MC, áȒȒƳȸɖǔǔ¨Jً!ǝȸǣɀɎƺȇɀȒȇ³ًRƏǕƺƳȒȒȸȇ¨ًIȸǣǴǼǣȇǸRáً!ǝȒɵ(Iً ȸȒɖɯƺȸÈًáǣɀȅƏȇ xً¨ȒɀɎȅƏ(³ًIǣȇǕǼƺɎȒȇhً ƺƏɀǼƺɵ«ًɮƏȇƳƺȇ ƺȸǕƺxًGuryev V. (2019) Nasal gene expression changes with inhaled corticosteroid treatment in asthma. Allergy. 2019 Jun ٠0ȵɖƫƏǝƺƏƳȒǔȵȸǣȇɎ١ِאדחב׏׎ِ׏׏׏׏ٖƏǼǼِ׏يƳȒǣِאא

3. Bernal V, Bischoff R, Guryev V, Grzegorczyk M, Horvatovich P (2019) Exact hypothesis testing for shrinkage based Gaussian Graphical Models. Bioinformatics. 2019 May 11. pii: ٠0ȵɖƫƏǝƺƏƳȒǔȵȸǣȇɎ١ِודבƫǣȒǣȇǔȒȸȅƏɎǣƬɀٖƫɎɿٖבח׏׎ِ׏׎يƳȒǣِודבƫɎɿ

ǝƏǣɀɀȒȇxh¨ً³ƏȇƳƺȸɀ(ًñǝƏȒæًxƏǼǝȒɎȸƏً¨ȒȸɖƫɀǸɵ(ً«ƏɖɀƬǝÁًJƏȸƳȇƺȸ0hً! .4 nًJɖȒnً!ȒǼǼǣȇɀ«nًIƏȇæًáƺȇhًRƏȇƳɀƏǸƺȸ«0ًIƏǣȸǼƺɵ³ًkȸȒȇƺȇƫƺȸǕ ȒƳȸǣǕɖƺɿ» ñzًkȒȇǕæًRȒȸȅȒɿƳǣƏȸǣIًnƺƺ(ًáƺȇǕƺȸxًRƏɀɎǣƺ«ًȇɎƏǸǣ(ًȇƏȇɎǝƏȸƏȅƏȇÁً Audano PA, Brand H, Cantsilieris S, Cao H, Cerveira E, Chen C, Chen X, Chin CS, Chong ñً!ǝɖƏȇǕzÁًnƏȅƫƺȸɎ!!ً!ǝɖȸƬǝ(xً!ǼƏȸǸƺnًIƏȸȸƺǼǼًIǼȒȸƺɀhًJƏǼƺƺɮÁًJȒȸǸǣȇ(Èً nƺƺh0ًnƺƺhًnƺƺًואGujral M, Guryev VًRƺƏɎȒȇáRًkȒȸǼƏƬǝhًkɖȅƏȸ³ًkɯȒȇhçًnƏȅ0Á xƏȸɎǣȇƺɿkًxƺǣƺȸɀ³ًxɖȇɀȒȇkxًzƏɮƏȸȸȒI!¨ًzƺǼɀȒȇٮá¨ًnƺƺ³¨ًnǣ³ًxƏȸǸɀ¨ًàǣƏɖƳ ƏȇƏǕǣȒɎȒȵȒɖǼȒɖ³ً¨ƏȇǕá!ًªǣɖçً«ȒɀƏȇǣȒJً¨ٮhًzȒƳɿƏǸ!ًzȒȒȸًkɵȸǣƏɿȒȵȒɖǼȒɖ ٮɵƏȇxً³ɎɜɎɿً³ȵǣƺȸǣȇǕɀ(!hًáƏȸƳًáƺǼƬǝ0ًæǣƏȒxًæɖáًñǝƏȇǕ!ًñǝɖªًñǝƺȇǕ» ȸƏƳǼƺɵæًnȒɯɵ0ًçƏǸȇƺƺȇ³ًxƬ!ƏȸȸȒǼǼ³ًhɖȇJً(ǣȇǕnًkȒǝ!nً«ƺȇ ًIǼǣƬƺǸ¨ً!ǝƺȇ kًJƺȸɀɎƺǣȇx ًkɯȒǸ¨çًnƏȇɀƳȒȸȵ¨xًxƏȸɎǝJÁً³ƺƫƏɎhً³ǝǣæً Əɀǝǣȸًçƺkً(ƺɮǣȇƺ ٣Multi-platformח׎׏א٢ِ!0ǣƬǝǼƺȸ00ًnƺƺ ³0ًÁƏǼǸȒɯɀǸǣx0ًxǣǼǼɀ«0ًxƏȸɀƬǝƏǼǼÁًkȒȸƫƺǼh discovery of haplotype-resolved structural variation in human genomes. Nat Commun. نɿٮזג׏ז׎ٮז׎׏ٮוהג׏גɀٖזב׏׎ِ׏׎يƳȒǣِגזו׏ي׏׎٢׏٣ٕהȵȸ׏ח׎׏א

٣ח׎׏א٢)Faiz A, van den Berge M, Vermeulen CJ, Ten Hacken NHT, Guryev Vً¨ȒɖɯƺǼɀ³ ِד AGER expression and alternative splicing in bronchial biopsies of smokers and never smokers. Respir Res. 2019 Apr 10;20(1):70. doi: 10.1186/s12931-019-1038-6.

ǼǣƬǝǔƺǼƳɎh¨ًƳƺhȒȇǕÁًkȒȸɎƺǸƏƏɀ«kًáɖæًnǣȇƳȇƺȸxًGuryev V, Hiemstra PS, Stolk ٮzǕ .6 ٣TGF-ɴƏƬɎǣɮƏɎǣȒȇǣȅȵƏǣȸɀˡƫȸȒƫǼƏɀɎƏƫǣǼǣɎɵɎȒɀɖȵȵȒȸɎח׎׏א٢»hًkȜȇǣǕɀǝȒǔǔxًJȒɀƺȇɀ adult lung epithelial progenitor cell organoid formation. Am J Physiol Lung Cell Mol ȵȸ׏׎ِח׎׏א0ȵɖƫِז׎׏א׎׎ِגƏǴȵǼɖȇǕِ׎׎ٖאד׏׎ِ׏׏يƳȒǣِזאnٮגn׏ي٢׏٣ו׏בhɖǼ׏ٕח׎׏אǝɵɀǣȒǼِ¨

7. de Jong TV, Moshkin YM, Guryev V (2019) Gene expression variability: the other يƳȒǣِזד׏ٮדג׏ي٣ד׏٢דxƏɵ׏ٕח׎׏א.dimension in transcriptome analysis. Physiol Genomics ِדxƏȸ׏ח׎׏א0ȵɖƫِז׎׏אِזאȵǝɵɀǣȒǼǕƺȇȒȅǣƬɀِ׎׎׏ٖאד׏׎ِ׏׏

ȇǕhًáȒǼƳǝɖǣɀ««ً ȒɖƳƺɯǣǴȇXxًɮƏȇƳƺȇ ƺȸǕًkǼɖǣɮƺȸhًkȒǸkًÁƺȸȵɀɎȸƏxxًGuryev .8 V, de Vries M Vermeulen CJ , Timens W, van den Berge M, Brandsma CA. (2019) Age- related gene and miRNA expression changes in airways of healthy individuals. Sci Rep. ׎ِٮבוזחבٮח׎׏ٮזחד׏גɀٖזב׏׎ِ׏׎يƳȒǣِדהובي٢׏٣חٕהxƏȸח׎׏א

(ÁƏɎƬǝƻxًnƏȇɀƳȒȸȵ¨xًGuryev V. (2019ٮȒȸɖƫɀǸɵ(ً³ƏȇƳƺȸɀ(ًÁƏɖƳɎً!ȒǼȒȅƻ¨ .9 breakpointR: an R/Bioconductor package to localize strand state changes in Strand-seq data. Bioinformatics. 2019 Aug 30. pii: btz681. doi: 10.1093/bioinformatics/btz681.

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ERIBA | Annual Report V2.indd 30 16-07-2020 21:00 10. van den Bos H, Bakker B, Taudt A, Guryev V, Colomé-Tatché M, Lansdorp PM, Foijer F, ٣ªɖƏȇɎǣˡƬƏɎǣȒȇȒǔȇƺɖȵǼȒǣƳɵǣȇxƏȅȅƏǼǣƏȇ³ɵɀɎƺȅɀِ Methodsח׎׏א³ȵǣƺȸǣȇǕɀ(!hِ٢ ِד׏ٗוٮ׏בחזٮחבחגٮ׏ٮזוחٖו׏׎ِ׏׎׎ي׎ِƳȒǣח׏ٮחד׏يהחז׏ٕח׎׏אxȒǼ ǣȒǼِ

XȅǸƏȅȵkً ƺȸȇƏǼàًJȸɿƺǕȒȸɿƬɵǸxًRȒȸɮƏɎȒɮǣƬǝ¨ًàƺȸȅƺɖǼƺȇ!hًRƺǣǴǣȇǸXRًGuryev .11 -٣Gene network approach reveals coח׎׏אVًkƺȸɀɎǴƺȇɀRxًɮƏȇƳƺȇ ƺȸǕƺxًIƏǣɿِ٢ يƳȒǣِדבזד׏ي٢׏٣חzȒɮ׏ٕח׎׏אexpression patterns in nasal and bronchial epithelium.³Ƭǣ«ƺȵِ ɴِٮבהח׎דٮח׎׏ٮזחד׏גɀٖזב׏׎ِ׏׎

ƏȇȇɖƏǼȸƺȵȒȸɎƏȸƺȇȒɯȵɖƫǼǣɀǝƺƳِז׎׏אȸƺȵȸǣȇɎɀǣȇƬǼɖƳƺƳǣȇ¨ن ׏ȵɖƫǼǣƬƏɎǣȒȇɀًˡɮƺƏȸƺȵȸƺȵȸǣȇɎɀِהɖɎȒǔ ُ

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ERIBA | Annual Report V2.indd 31 16-07-2020 21:00 Funding/Grants

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ERIBA | Annual Report V2.indd 32 16-07-2020 21:00 Research proposals awarded in 2019

Principal Investigator/ Role Grant Title Budget Researcher ׎׎דِבڡ Amanda Assoni Applicant (ƺ!ȒƬǸ Restoring VAPB levels in iPS –derived motor neurons from ALS patients

׎׎דِבڡ Christy Hong Applicant (ƺ!ȒƬǸ Investigation of the underlying biology behind nuclear localization of cGAS in breast cancer cells ׎׎דِבڡ ThijmenVan Appilcant (ƺ!ȒƬǸ caloric restriction to reduce Vliet toxicity of chemotherapy- induced senescence

׎׎דِבڡ Britt Sterken Applicant (ƺ!ȒƬǸ The role of the C/EBPȕ isoforms in breast cancer

׎׎דِבڡ Inna Armandari Applicant (ƺ!ȒƬǸ Understanding the Role of ǣȇ³ȒȇǣƬRƺƳǕƺǝȒǕ)אkxÁ Medulloblastoma

׎דזِזדוڡ xƏȸƬȒ(ƺȅƏȸǣƏ Co- ñȒȇxɯ SMARTage; part of Vitality applicant publiek- Oriented Innovation for the private Lifecourse of the Ageing partnerships: Society (VOILA) Parkinson en Vitaliteit & Levensloop

בובِחדבڡ Stem cell differentiation ٮkn0XzٮEugene Applicant 0zá Berezikov set 02 programs in the regenerative ˢƏɎɯȒȸȅxƏƬȸȒɀɎȒȅɖȅ Lignano

׎׎׎ِד׏הڡ Gerald de Haan Applicant káI Characterizing and targeting CBX7 regulated selfrenewal pathways in leukemia

Floris Foijer Applicant káI ScreeninC: a national € 600.000 infrastructure for functional genome editing and large scale funtional screening

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ERIBA | Annual Report V2.indd 33 16-07-2020 21:00 Principal Investigator/ Role Grant Title Budget Researcher ƬƏȵɎɖȸƺٖȅƏɀɀ € 76.800ژJohn LaCava Applicant Public- ǔˡȇǣɎɵ Private spectrometry screening Partnership, combined with mass ɀƏȅȵǼƺژHealth ȵǝȒɎȒȅƺɎȸɵɎȒƏɀɀƺɀɀ Holland heterogeneity and predict macromolecular topologies John LaCava Applicant kƏȇǸƺȸ Targeted mass spectrometry € 3.000 Research detection of a parasitic gene Fonds product in human cancers

Ellen Nollen (ǣɀƬȒɮƺȸǣȇǕɎǝƺȸƏȵƺɖɎǣƬ € 208.000 targets to rescue motor Applicant ALS impairment using small animal Foundation model for ALS (SMALLS)

Sahil Gupta Applicant (IJ Mapping the initiating steps € 67.008 of aneuploidy and aneuploidy tolerization in tumorigenesis

Applicant k«I Finding the drivers of € 3.000 ژژژژژژژژژژژژnǣȇñǝȒɖ aneuploidy-induced senescence Applicant CSC The consequences of € 64.800 ژژژژژژژژژ³ǣȷǣñƺȇǕ chromosomal instability during development and in ژɎɖȅȒȸǣǕƺȇƺɀǣɀǣȇɿƺƫȸƏˡɀǝ

KWF: (ɖɎƬǝ!ƏȇƬƺȸ³ȒƬǣƺɎɵ NWO:zƺɎǝƺȸǼƏȇƳɀ ȸǕƏȇǣɀƏɎǣȒȇǔȒȸ³ƬǣƺȇɎǣˡƬ«ƺɀƺƏȸƬǝ De Cock:hƏȇkȒȸȇƺǼǣɀƳƺ!ȒƬǸIȒɖȇƳƏɎǣȒȇ UMCG: University Medical Center Groningen/Cancer Research Funds ALS Foundation: Amyotrophic lateral sclerosis Foundation CSC: Chinese Scholarship Council

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ERIBA | Annual Report V2.indd 34 16-07-2020 21:00 Invited Speakers

In 2019, many eminent scientists have been invited to give talks and lectures in ERIBA and University Medical Center Groningen.

Speaker Host Title of talk/lecture University / Event Institute Iris Gerald Beyond GWAS - (ƺȵƏȸɎȅƺȇɎȒǔ Friday Jonkers de Haan understanding how Genetics, UMCG afternoon genetically associated meeting regions contribute to ٹژƬƺǼǣƏƬƳǣɀƺƏɀƺ

Hans Gerald Fibroblast Growth (ƺȵƏȸɎȅƺȇɎ Friday Jonker de Haan Factors in the regulation of Pediatrics, afternoon of metabolic healthspan UMCG meeting and lifespan”

George Michael Going from ‘omics’ data AMC in Friday Janssen Chang to therapeutics: a focus Amsterdam afternoon on aging” meeting

XƳƺȇɎǣˡƬƏɎǣȒȇȒǔȇȒɮƺǼ (ƺȵƏȸɎȅƺȇɎȒǔ Fridayٹ Peter van der Gerald Meer de Haan targets in heart failure” Cardiology and afternoon Thorax Surgery, meeting UMCG

Peter Marco The dynamic epigenome Sanford Molecular Adams (ƺȅƏȸǣƏ - a challenge for healthy Burnham Medicine Series aging Prebys Medical (ǣɀƬȒɮƺȸɵ Institute, La Jolla CA, USA

Burkhard Marco The T cell/phagocyte 0ÁRًñɜȸǣƬǝً Molecular Becher (ƺȅƏȸǣƏ interface during chronic Switzerland Medicine Series and ǣȇˢƏȅȅƏɎǣȒȇ Jon Laman

Shelley Gerald de Bare essentials of , San Molecular Buffenstein Haan aging; a naked mole rat Francisco, USA Medicine Series perspective

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ERIBA | Annual Report V2.indd 35 16-07-2020 21:01 Speaker Host Title of talk/lecture University / Event Institute Adnan Halim John Protein O-glycosylation Center for Molecular LaCava in human health and Glycomics Medicine Series disease (CCG), University of Copenhagen, (ƺȇȅƏȸǸ

Bernhard Floris Pooled CRISPR/Cas9 High CRISPR/Cas9 Schmierer Foijer and genetic screening: Throughput Technology Jonas methods, applications Genome Symposium Seiler and an unexpected Engineering, ˡȇƳǣȇǕ National Facility | Science for Life Lab, Stockholm, Sweden

Michael Cor Metabolic Control of 0ÁRñɜȸǣƬǝً Molecular Ristow Calkhoven Healthy Aging Switzerland Medicine Series

Nanette Floris The impact of distinct Hubrecht Friday Jellema Foijer levels of chromosomal institute afternoon instability on cancer” meeting

Jeroen Eugene Heart regeneration: Hubrecht Molecular Bakkers Berezikov ǼƺɀɀȒȇɀǔȸȒȅɿƺƫȸƏˡɀǝ Instituut, Medicine Series and Utrecht Judith Paridaen

Eline xƺɎƏƫȒǼǣƬȵȸȒˡǼǣȇǕȒǔ Leiden 3rd Biology Slagboom human health, ageing University, The of Ageing and mortality netherlands meeting 2019

Stephen The Nutritional The University 3rd Biology Simpson Geometry of Aging and of Sydney, of Ageing Metabolic Health Australia meeting 2019

Maria Teresa Telomeres and the route CNRS, France 3rd Biology Teixeira to senescence of Ageing meeting 2019

Jan Vijg Single-cell analysis of Albert Einstein 3rd Biology genome instability in College of of Ageing ageing medicine, meeting 2019 United States of America

Francis Irreversible genome CRCHUM, 3rd Biology Rodier damage from teomeric Canada of Ageing fusions estblish meeting 2019 replicative senescence in normal human cells

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ERIBA | Annual Report V2.indd 36 16-07-2020 21:01 Speaker Host Title of talk/lecture University / Event Institute Marie Noelle The nuclear pore CNRS, France 3rd Biology Simon complex prevents sister of Ageing chromtid recombination meeting 2019 at telomeres during replicative senescence

Titia de Lange Telomeres and The Rockefeller 3rd Biology cancer:tumor University, of Ageing suppression and united States of meeting 2019 genome instability America

Toren Finkel Mitochondria, University of 3rd Biology metabolism and ageing. Pittsburgh, of Ageing United States of meeting 2019 America

Patricia Boya Autophagy in CSIC, Madrid, 3rd Biology neurons:from Spain of Ageing development to aging meeting 2019

Riekelt Cross-compartmental University 3rd Biology Houtkooper proteostasis in Medical Center of Ageing Amsterdam, The meeting 2019 Netherlands

Natascia Mitochondrial Heinrich Heine 3rd Biology Ventura bionergetic changes University, of Ageing during development as Germany meeting 2019 an indicator of C. elegans health-span

Peter Adams Mitochondrial-nuclear Sanford 3rd Biology retrograde signaling Burnham of Ageing drives senescence- Prebys Medical meeting 2019 associated infmamation (ǣɀƬȒɮƺȸɵ and is a target for Institute, healthy aging United States of America

Christof (zƳƺȅƺɎǝɵǼƏɎǣȒȇƏȇƳ Institute of 3rd Biology Niehrs aging Molecular of Ageing Biology, meeting 2019 Germany

Tamir Global changes The University 3rd Biology Chandra accompany and of Edinburgh, of Ageing distinguish primary and United meeting 2019 secondary senescence kǣȇǕƳȒȅ induction

Jan van Understanding in vivio Mayo Clinic, 3rd Biology (ƺɖȸɀƺȇ senescence to improve United States Of of Ageing healthy aging Americ meeting 2019

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ERIBA | Annual Report V2.indd 37 16-07-2020 21:01 Speaker Host Title of talk/lecture University / Event Institute Manuel Identifying novel Health Research 3rd Biology Collado senelotic compounds Institue of of Ageing by high throughput Santiago de meeting 2019 screening Compostela ٢X(X³٣³ȵƏǣȇ

Ines Senescent cells Mayo Clinic, 3rd Biology united States of of Ageing בד׏ǔȸȒȅȵאSturmlechner ɖȇƬȒɖȵǼƺȵ to sustain cell viability, America meeting 2019 cell cycle arrest and immunosurveillance.

Christiaan Clinical Trials Originated University of 3rd Biology Leeuwen from Findings from Florida of Ageing burgh Biolgy of Aging Research meeting 2019

Richard Lower germline University of 3rd Biology Cawton mutation rates in Utah, United of Ageing young adults predict States of meeting 2019 longer lives and longer America reproductive lifespans

Yves Barral Ageing: some insights Institute of 3rd Biology from a good old fungus Biochemistry/ of Ageing 0ÁRñɖȸǣƬǝً meeting 2019 Switzerland

Simon Alberti Phase seperation as Max Planck 3rd Biology astress survival strategy Institute of of Ageing Molecular meeting 2019 Cell Biology and Genetics, Germany

Sebastian A novel University of 3rd Biology Iben pathomechanism:are Ulm, Germany of Ageing Cockayen syndrome meeting 2019 and trichothiodystrophy ribosomopathies?

Max Planck 3rd Biology ّ אIڻ)xƏȸɎǣȇ(ƺȇɿƺǼ ƬɎǣɮƏɎǣȒȇȒǔƺǼ Extends lifespan in Institute for of Ageing C.elegans by promoting Biology of meeting 2019 selective mRNA Ageing, translation Germany

Patrick van Molecular structure ñƺȸȇǣǸƺXȇɀɎǣɎɖɎƺ 3rd Biology der Wel and biological activity for Advanced of Ageing of protein aggregates Materialse, The meeting 2019 assocated with Netherlands huntington disease

Hiromitsu Growing organs in Stanford 3rd Biology Nakauchi vivo:iPS cell-derived, University, of Ageing xeno-created organs for United states of meeting 2019 transplantation America

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ERIBA | Annual Report V2.indd 38 16-07-2020 21:01 Speaker Host Title of talk/lecture University / Event Institute Claudia Prospective isolation of Leibniz- 3rd Biology Waskow the non-hematopoietic Institute on of Ageing meeting 2019 ٮIȸǣɎɿڻ)stem cell niche and its ǕǣȇǕً molecular cross-talk to Lipmann- hemaopoietic stem cells Institute (FLI), Germany

Ruzhica Repetitive Exposure to German Cancer 3rd Biology Bogeska ǣȇˢƏȅȅƏɎȒȸɵ³Ɏȸƺɀɀ Research of Ageing meeting 2019 kIñ٣ً)Leads to Hematopoietic !ƺȇɎƺȸ٢ Stem Cell Atriition and Germany Hematopoietic Tissue Failure during Ageing

kȸǣɀɎǣȇƏ Age-related clonal University of 3rd Biology kǣȸɀƬǝȇƺȸ haemopoiesis and Glasgow, United of Ageing myeloproliferative kǣȇǕƳȒȅ meeting 2019 disease are associated with increased epigenetic age

Lenhard Mitochondrial Leibniz Institute 3rd Biology Rudolph dysfunction limits on Aging-FLI, of Ageing metabolic plasticity of Germany meeting 2019 aging stem cells to adapt to changes in nutrient availibility

Matt Targeting aging through University of 3rd Biology mTOR inhibition Washington, of Ageing kƏƺƫƺȸǼƺǣȇ United States of meeting 2019 America

Prof. Robert Victor Workshop on University of extra seminar/ W Williams Guryev GeneNetwork - online Tennessee defense Tristan platform for multiomics de Jong data integration”

Ben Optogenetic modulation Biomedecial Fish Giepmans of exocrine cells leading Sciences and Technologie to beta cell stress in Cell Systems, symposium ɿƺƫȸƏˡɀǝ UMCG

Luiza Reali ¨0ÁǣȅƏǕǣȇǕǣȇɿƺƫȸƏˡɀǝ Nuclear Fish Nazario Medicine, Technologie UMCG symposium

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ERIBA | Annual Report V2.indd 39 16-07-2020 21:01 Speaker Host Title of talk/lecture University / Event Institute Jeroen Haert Hubrecht Fish Bakkers regeneration:lessons Institute for Technologie ǔȸȒȅɿƺƫȸƏˡɀǝ (ƺɮƺǼȒȵȅƺȇɎ symposium Biology and Stem Cell Research, Utrecht

Catriene XȇɎȸȒƳɖƬɎǣȒȇ!(¨Iǣɀǝ !(¨ًÈx!J Fish Thuring Facilities Technologie symposium

Fabrizio (zƳƏȅƏǕƺȸƺɀȵȒȇɀƺ IFOM, Milan, xƏȸƬȒ(ƺȅƏȸǣƏ d’Adda di in aging and its control Italy Fagagna by non coding RNA

Lluis Morey John Role of polycomb Sylvester Molecular LaCava complexes in stem cells Comprehensive Medicine Series and cancer Cancer Center, Cancer Epigenetics ȸȒǕȸƏȅً(ƺȵɎِ¨ Of Human Genetics, University of Miami, Miller School of Medicine, Miami, USA

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ERIBA | Annual Report V2.indd 40 16-07-2020 21:01 41

ERIBA | Annual Report V2.indd 41 16-07-2020 21:01 People

EMPLOYEES STAFF MEMBERS UNDER 40 2019 2019 99 73%

2013 - 81 2016 - 92 2013 - 69% 2016 - 61% 2014 - 89 2017 - 107 2014 - 63% 2017 - 76% 2015 - 89 2018 - 100 2015 - 63% 2018 - 72%

FEMALE EMPLOYEES INTERNS 2019 2019 62% 48

2013 - 60% 2016 - 55% 2013 - 17 2016 - 26 2014 - 56% 2017 - 54% 2014 - 41 2017 - 49 2015 - 56% 2018 - 60% 2015 - 41 2018 - 45

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ERIBA | Annual Report V2.indd 42 16-07-2020 21:01 USA MEXICO NUMBER OF NATIONALITIES CHINA SPAIN CZECH REPUBLIC BRAZIL THE NETHERLANDS ITALY 27 GERMANY LEBANON SAUDI-ARABIA BULGARIA BOSNIA AND RUSSIA KAZAKHSTAN INDONESIA HERZEGOVINA PERU INDIA HUNGARY UNITED KINGDOM BELGIUM CHILE AUSTRIA HONGKONG TURKEY GREECE COLOMBIA

INTERNATIONALS DOCTORAL STUDENTS HOSTED BY ERIBA

2019 2019 49% 26

2013 - 47% 2016 - 45% 2013 - 22 2016 - 27 2014 - 48% 2017 - 49% 2014 - 22 2017 - 44 2015 - 47% 2018 - 46% 2015 - 26 2018 - 39

(10 of these students hosted by ERIBA under the GSMS Bursary Scheme)

MANAGEMENT TEAM ERIBA

Henk Heidekamp, xƏȇƏǕǣȇǕ(ǣȸƺƬɎȒȸ Nina Kool, «ƺɀƺƏȸƬǝ(ƺɮƺǼȒȵȅƺȇɎ ǔˡƬƺɀɀǣɀɎƏȇɎ Arnoud Rozema, Staff Advisor Annet Vos-Hassing, Secretary Kevin Huizinga, Financial Controller Sylvia Hoks, Secretary Megha Upadhyay-Pandey, Research Coordinator Alida de Haan, Secretary Yin Fai Chan, Technician (general support)

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ERIBA | Annual Report V2.indd 43 16-07-2020 21:01 Facilities

Education

Outreach & Dissemination

5EKGNěKĂE Advisory Board

Sponsors

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ERIBA | Annual Report V2.indd 44 16-07-2020 21:01 45

ERIBA | Annual Report V2.indd 45 16-07-2020 21:01 Facilities

iPSC/CRISPR

The discovery of protocols to reprogram somatic cells into induced pluripotent stem cells (iP- SCs) is revolutionising regenerative medicine. The therapeutic promise of iPSC technology in- cludes the production of isogenic cell lineages and (in the future) tissues to replace body parts that can be autografted in patients when organs are failing. Importantly, when combined with CRISPR genome engineering technology, iPSC technology can be used to cure (mono) genetic diseases, by repairing the disease-causing mutation in patient-derived iPSCs and by differentiating the repaired cells into functional tissues and transplanting them back into the patient. The iPSC/CRISPR centre at ERIBA aims to contribute to this therapeutic promise. For this, we help UMCG and RUG employees with deriving iPSCs and establishing differenti- ated cultures from these iPSCs. Furthermore, we help our customers with CRISPR genome engineering, including making knockout cell lines, engineering point mutations, tagging en- dogenous genes, etc. in various cell lines, including iPSCs. Furthermore, we facilitate genome- wide CRISPR functional screens and we engineer mouse models using CRISPR technology. Since the start of the centre in 2014, we accommodated ~100 different projects, and we initi- ated ~30 new projects that include iPSC projects, and CRISPR genome engineering projects in cells and in mice. We implemented a number of differentiation protocols and protocols to grow cerebral organoids and validated the reagents for genome-wide CRISPR screens. Impor- ٮɎƏȇɎǼɵًɯƺɎȸƏǣȇƺƳɀƺɮƺȸƏǼ¨ǝ(ɀɎɖƳƺȇɎɀǣȇƳƺȸǣɮǣȇǕƏȇƳȅƏǣȇɎƏǣȇǣȇǕǣ¨³!ɀƏȇƳǣȇƳǣǔǔƺȸƺȇɎǣƏɎ ing iPSCs into various cell types. Furthermore, we hosted MSc students for internships and we organised the CRISPR genome engineering course for Biomedical Sciences MSc students. We expect to accommodate several new large-scale projects, as we appointed more postdocs, and we will likely invest in infrastructure to automate iPSC culture, thus drastically increasing our capacity for iPSC lines.

Who Contact Floris Foijer - Coordinator IPSC/CRISPR European Research Institute for the Biology facility of Ageing, Bart van de Sluis - Coordinator CRISPR mice University Medical Centre Groningen Arun Thiruvalluvan - Postdoctoral Fellow Building 3226, PO Box 196 ׎דDr. René Wardenaar - Posdoctoral Fellow XȇɎƺȸȇƏǼñǣȵ!ȒƳƺI ׎׎(JȸȒȇǣȇǕƺȇוח Sahil Gupta - Postdoctoral Fellow ׎וזגאואדה׏בڷ Jonathan Seiler - Postdocoral Fellow Mathilde Broekhuis - Technician [email protected] Eslie Huizinga - Technician Eriba.umcg.nl/ipsc-crispr-facility/

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ERIBA | Annual Report V2.indd 46 16-07-2020 21:01 Fish facility

٣ǣȇɎǝƺÈȇǣɮƺȸɀǣɎɵxƺƳǣƬƏǼ!ƺȇɎƺȸJȸȒȇǣȇǕƺȇǣɀȒȇƺȒǔɎǝƺ¨)!Áǝƺ!ƺȇɎȸƏǼȇǣȅƏǼIƏƬǣǼǣɎɵ٢ ƏƬƏƳƺȅǣƬƺɴȵƺȸǣȅƺȇɎƏǼƏȇǣȅƏǼǣȇɀɎǣɎɖɎǣȒȇɀǣȇɎǝƺzƺɎǝƺȸǼƏȇƳɀِÁǝƺ!(¨ǣɀƏǔƏƬǣǼǣɎɵɯǝƺȸƺב׏ ¨)!ƺɴȵƺȸǣȅƺȇɎƏǼƏȇǣȅƏǼɀƏȸƺǝȒɖɀƺƳًƏȇƳɯǝƺȸƺƏȇǣȅƏǼƺɴȵƺȸǣȅƺȇɎƏɎǣȒȇǣɀƬȒȇƳɖƬɎƺƳِÁǝƺ supports and facilitates research and education projects involving vertebrate experimental ƏȇǣȅƏǼɀًɀɖƬǝƏɀȸȒƳƺȇɎɀƏȇƳˡɀǝِ

-ƏȸɎǝȒɖɀǣȇǕǣɀɀɖȵٮɎǝƺٮȒǔٮƏˡɀǝǔƏƬǣǼǣɎɵɯƏɀƺɀɎƏƫǼǣɀǝƺƳɯǣɎǝǣȇɎǝƺ!(¨ًɯǝƺȸƺɀɎƏɎƺًה׎׏אXȇ ƏȇǣȒ)ǸǣǼǼǣˡɀǝ٢zȒɎǝȒƫȸƏȇƬǝǣɖɀǔɖȸɿƺȸǣ٣ًƏȇƳɿƺƫȸƏˡɀǝ٢يȵǼǣƺƳǔȒȸɎɯȒɀȵƺƬǣƺɀȒǔɀȅƏǼǼˡɀǝ ȸƺȸǣȒ٣ِkǣǼǼǣˡɀǝƏȸƺɎǝƺɀǝȒȸɎƺɀɎǼǣɮǣȇǕɮƺȸɎƺƫȸƏɎƺƺɴȵƺȸǣȅƺȇɎƏǼƏȇǣȅƏǼɀɵɀɎƺȅًɯǝǣƬǝȅƏǸƺɀ it very suitable for studying ageing processes. They were introduced by the Berezikov lab in the ERIBA as a new model organism to study the biology of ageing in the ERIBA and UMCG. ɖȸȸƺȇɎǼɵًɎǝƺ!(¨ǣɀɎǝƺȒȇǼɵǔƏƬǣǼǣɎɵǣȇɎǝƺzƺɎǝƺȸǼƏȇƳɀɎǝƏɎǝȒɖɀƺɀǸǣǼǼǣˡɀǝِñƺƫȸƏˡɀǝƏȸƺƏ! very versatile vertebrate experimental animal system that is used extensively in biomedical research, and constitute a cheaper and easy-to-work-with alternative to rodents.

Key expertise and services

ɎƏǸƺȸɀɎȸƏǣȇƺƳǣȇƫȸƺƺƳǣȇǕًȸƺƏȸǣȇǕȒǔˡɀǝǼƏȸɮƏƺًǕƺȇƺȸƏǼƬƏȸƺٮƺƳǣƬƏɎƺƳƏȇǣȅƏǼƬƏȸƺ) % ƏȇƳǝƺƏǼɎǝɀƺȸɮǣƬƺɀǣȇɀȅƏǼǼˡɀǝɀȵƺƬǣƺɀ % (ƺƳǣƬƏɎƺƳȅǣƬȸȒǣȇǴƺƬɎǣȒȇƏȇƳƺȵǣˢɖȒȸƺɀƬƺȇƬƺɀɎƺȸƺȒȅǣƬȸȒɀƬȒȵɵɀƺɎɖȵɀǔȒȸɮǣɀɖƏǼǣȇ- ɀȵƺƬɎǣȒȇًƏȇƏǼɵɀǣɀًȅƏȇǣȵɖǼƏɎǣȒȇƏȇƳȅǣƬȸȒǣȇǴƺƬɎǣȒȇȒǔɿƺƫȸƏˡɀǝƏȇƳǸǣǼǼǣˡɀǝƺȅƫȸɵȒɀ % (ƺƳǣƬƏɎƺƳǣȇƬɖƫƏɎȒȸɀǔȒȸǝȒɖɀǣȇǕˡɀǝƺȅƫȸɵȒɀ ɎɵȵƺˡɀǝًɀɖƬǝƏɀ ًÁnƏȇƳ!Əɀȵƺȸ٢ɎȸƏȇɀȵƏȸƺȇɎ٣ٮɮƏǣǼƏƫǣǼǣɎɵȒǔɀƺɮƺȸƏǼɀɎȸƏǣȇɀȒǔɯǣǼƳ % ɿƺƫȸƏˡɀǝ % Breeding services to obtain embryos of wild-type, and if required, other strains ³ɖȵȵȒȸɎƏȇƳƏƳɮǣƬƺȸƺǕƏȸƳǣȇǕǕƺȇȒȅǣƬȅȒƳǣˡƬƏɎǣȒȇȅƺɎǝȒƳɀًɀɖƬǝƏɀɎȸƏȇɀǕƺȇƺɀǣɀ % ȅƺƳǣƏɎƺƳǕƺȇȒȅǣƬȅȒƳǣˡƬƏɎǣȒȇɀٮחƏȇƳ!«X³¨«ٖƬƏɀ ÁȸƏǣȇǣȇǕȒǔȇƺɯɖɀƺȸɀǣȇˡɀǝƺɴȵƺȸǣȅƺȇɎƏɎǣȒȇ٢ȇƺɴɎɎȒȒƫǼǣǕƏɎȒȸɵƬȒɖȸɀƺȒȇnƏƫȒȸƏɎȒȸɵ % Animal Science) % Breeding and care taking, biotechnical support, micro-surgical support, imaging sup- port and animal welfare monitoring

Who Contact

٣Èx!J¨)!ƺȇɎȸƏǼȇǣȅƏǼIƏƬǣǼǣɎɵ٢! ٫0«X ¨X٢ǸǣǼǼǣˡɀǝƺɴȵƺȸɎ٣ Eugene Berezikov Joscha Muck – Postdoctoral fellow, ERIBA Antonius Deusinglaan 1 9713 AV Groningen ٢ǸǣǼǼǣˡɀǝƺɴȵƺȸɎ٣ hɖƳǣɎǝ¨ƏȸǣƳƏƺȇ٫0«X ¨X٢ɿƺƫȸƏˡɀǝƺɴȵƺȸɎ٣ Nynke Oosterhof – postdoctoral felow, ERIBA The Netherlands [email protected] ٢ɿƺƫȸƏˡɀǝƺɴȵƺȸɎ٣ ¨)!Alex Kluppel٫xƏȇƏǕƺȸ [email protected] ǔˡƬƺȸً Catriene Thuring٫ȇǣȅƏǼáƺǼǔƏȸƺ (ƺȵɖɎɵRƺƏƳ!(¨

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ERIBA | Annual Report V2.indd 47 16-07-2020 21:01 Sequencing Facility

Next generation sequencing (NGS) technology is revolutionizing medicine and life sciences and has become a routine tool to assess the genomes, epigenomes and transcriptomes of cul- tured cells, (liquid) biopsies, and primary tissue/disease samples. In May 2019, the Research Se- ȷɖƺȇƬǣȇǕIƏƬǣǼǣɎɵɯƏɀȒǔˡƬǣƏǼǼɵƺɀɎƏƫǼǣɀǝƺƳɯǣɎǝǣȇɎǝƺ0«X ÁƺƬǝȇȒǼȒǕɵ!ƺȇɎƺȸًƏɀƏƳƺƳǣƬƏɎƺƳ research infrastructure to provide support for NGS-based projects for UMCG and RUG research groups. For this, we will not only facilitate the expeditious sequencing of NGS libraries either prepared by research groups themselves or by the facility on behalf of the researcher, but also implement the latest NGS techniques used in medicine and life sciences research, and (co)de- velop and implement new state-of-the-art NGS techniques to keep NGS-dependent research in the UMCG at the forefront. Furthermore, we advise the researchers on the set-up of their NGS experiments and train researchers in the production of NGS libraries if they would prefer to do this themselves. As a spin-off from the Peter Lansdorp research group, we are experts in -ɀƺȷɎƺƬǝȇȒǼٮƬƺǼǼ(zɀƺȷɖƺȇƬǣȇǕƏȇƳɎǝƺȒȇǼɵɀƺȷɖƺȇƬǣȇǕǔƏƬǣǼǣɎɵȒǔǔƺȸǣȇǕɎǝƺ³ɎȸƏȇƳٮɀǣȇǕǼƺ ogy as a service. Strand-seq is a powerful tool to identify besides copy number alterations also copy-number neutral structural genomic aberrations such at inversions and translocations, all at the single cell level thereby preserving tissue heterogeneity. In 2019, we have generated over -׎ƳǣǔǔƺȸƺȇɎɀƏȅȵǼƺɀِxȒȸƺגבɀƺȷǼǣƫȸƏȸǣƺɀƳƺȸǣɮƺƳǔȸȒȅƏȵȵȸȒɴǣȅƏɎƺǼɵٮƬƺǼǼ(zٮ׎׎׎ɀǣȇǕǼƺًג׏ over, we facilitated ~100 sequencing runs in total. Although we could only facilitate small NGS ٮɯƺƺɴȵƺƬɎɎȒƏƬƬȒȅȅȒƳƏɎƺȅƏȇɵȇƺɯǼƏȸǕƺًח׎׏אɀƺȷ٣ǣȇٮɀƺȷً(zٮ!ɀƺȷًÁٮz»ȵȸȒǴƺƬɎɀ٢ scale projects as we have invested in infrastructure to automate library preparation thereby drastically increasing our capacity for many NGS applications.

Who Contact Diana Spierings – Coordinator Research Se- European Research Institute for the Biology quencing Facility of Ageing, University Medical Centre Gronin- gen Nancy Halsema – Technician Building 3226, PO Box 196 Karina Wakker-Hoekstra – Technician ׎דXȇɎƺȸȇƏǼñǣȵ!ȒƳƺI Jennefer Beenen – Technician ׎׎(JȸȒȇǣȇǕƺȇוח

׏הזגאואדה׏בڷ [email protected]

http://eriba.umcg.nl/research-sequencing- facility/

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ERIBA | Annual Report V2.indd 48 16-07-2020 21:01 49

ERIBA | Annual Report V2.indd 49 16-07-2020 21:01 Education

ERIBA scientists are involved in multiple education activities. The list below is a selection of major contributions to teaching. It excludes a large number of individual lectures and undergraduate student internships

Molecular and Genetic Age Research ERIBA

10 ECTS, 20 BSc. Biology, and Life Science and Technology students

ژȒȸ!ƏǼǸǝȒɮƺȇ!ژيȒȒȸƳǣȇƏɎȒȸ!

Objectives: A laboratory research course with research topics covering a broad range of tech- niques and model systems related to ageing, lifespan and age-related diseases. Topics may involve (stem) cells, yeast, worms, mice, and cover the biological processes of signal transduc- ɎȸƏȇɀǼƏɎǣȒȇƏǼ ȅȒƳǣˡƬƏɎǣȒȇً ȵȸȒɎƺǣȇ ǝȒȅƺȒɀɎƏɀǣɀً ƺȇƺȸǕɵٮɎǣȒȇً ɎȸƏȇɀƬȸǣȵɎǣȒȇً ɎȸƏȇɀǼƏɎǣȒȇً ȵȒɀɎ ژȅƺɎƏƫȒǼǣɀȅًƬǝȸȒȅȒɀȒȅƺƫǣȒǼȒǕɵًǕƺȇƺɎǣƬɀƏȇƳƺȵǣǕƺȇƺɎǣƬɀًƏȇƳƫǣȒǣȇǔȒȸȅƏɎǣƬɀِ

CRISPR genome engineering

׎ɀɎɖƳƺȇɎɀבÁ³ٕ!0ד Coordinator: Floris Foijer

Objectives: In this course, MSc learn the basics of CRISPR engineering. Students learn about the history and various applications of CRISPR including knockouts, knockins, CRISPR I, CRIS- ȒȇƺɴȵƺȸǣƺȇƬƺǣȇٮɎǝƺɵǕƺɎǝƏȇƳɀژɯǣƳƺɀƬȸƺƺȇɀِIɖȸɎǝƺȸȅȒȸƺًٮƏًȅɖɎƏɎǣȒȇɀƏȇƳǕƺȇȒȅƺ»¨ the design of guide RNAs and genome editing tools and apply them in the lab. Finally, they combine their newly acquired expertise in an assignment in which they design a complete X³¨«ɀɎȸƏɎƺǕɵǔȒȸƏˡƬɎǣɮƺȵȸȒǴƺƬɎِ»!

Models systems in Ageing research

3 ECTS; 4 students (2019), 8 students (2020)

Coordinator: Floris Foijer

Objectives: In this JSM course, third year medical students explore fundamental biology and are exposed to several of the model organisms we use at ERIBA for ageing-related research. Students discuss advantages and disadvantages of the model organisms with researchers on the lab. and study relevant papers that make use of the model organisms. In small groups, they compare the feasibility of 2-3 models Ito study (aspects of) a particular disease and discuss the advantages and disadvantages of these models in this setting.

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ERIBA | Annual Report V2.indd 50 16-07-2020 21:01 Specialization Track on the Biology of Ageing

׏ɀɎɖƳƺȇɎɀאژxƏɀɎƺȸɀɎɖƳƺȇɎɀǣȇ ǣȒȅƺƳǣƬƏǼ³ƬǣƺȇƬƺɀ٢Iáz٣ً

Coordinator: Ellen Nollen/Floris Foijer

ȒȒȸƳǣȇƏɎǣȒȇƏȇƳȅƺȇɎȒȸǣȇǕȒǔɀɎɖƳƺȇɎɎǝƏɎɯƏȇɎɎȒɀȵƺƬǣƏǼǣɿƺǣȇƏǕƺǣȇǕȸƺɀƺƏȸƬǝِ!ژ:Objectives The research track includes courses have been developed and are coordinated by ERIBA PIs, which are i) Molecular Biology of Ageing course, ii) Current themes in Healthy Ageing, and iii) CRISPR genome engineering.

Molecular Biology of Ageing and Age related Disease”

׎x³ƬƫǣȒȅƺƳǣƬƏǼɀɎɖƳƺȇɎɀבÁ³ً!0ד

Coordinator: Liesbeth Veenhoff

Objectives: In this course we focus on the molecular and cellular mechanisms by which tissue and organ function deteriorate and homeostasis fails, resulting in ageing and age related dis- ease. We present the model systems and experimental strategies that are used in ageing re- ɀƺƏȸƬǝِÁǝǣɀƬȒɖȸɀƺǣɀɀɖȵȵȒȸɎƺƳƫɵƏɎƺƏȅȒǔɀȵƺƬǣƏǼǣɀɎɀǣȇƳǣǔǔƺȸƺȇɎˡƺǼƳɀȒǔƏǕƺǣȇǕɯǝȒȵȸȒɮǣƳƺ lectures and reading material. The course will be further supported by materials from an online course “Why do we age? The molecular mechanisms of ageing”. The course unit is compulsory for the ageing track and is an elective in the other tracks of the programs.

Exam committee Behavioural and Cognitive Neuroscience Research Mas- ter (BCN-ReMa)

Member, Secretary; Liesbeth Veenhoff

The board of examiners assesses the results of teaching for individual BCN-ReMa students, ƏȇƳǕɖƏȸƏȇɎƺƺɀɎǝƺȷɖƏǼǣɎɵȒǔƺɴƏȅǣȇƏɎǣȒȇɀƏȇƳˡȇƏǼƏɀɀƺɀɀȅƺȇɎɀِ

Opleidingscommissie Molecular Medicine and Innovative Treatment (MMIT)

Member: Liesbeth Veenhoff

The program committee gives advice to ensure the quality of the educational program.

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ERIBA | Annual Report V2.indd 51 16-07-2020 21:01 Current Themes in Healthy Ageing

ژx³Ƭ ǣȒȅƺƳǣƬƏǼ³ƬǣƺȇƬƺɀɀɎɖƳƺȇɎɀژ׏׎ژÁ³ً!0ד

ژhɖƳǣɎǝ¨ƏȸǣƳƏƺȇژƏȇƳژxƏȸƬȒ(ƺȅƏȸǣƏژيȒȒȸƳǣȇƏɎȒȸɀ!

Objectives: Learn leading edge ageing research and interact with prominent ageing scientists ɀƬǣƺȇɎǣˡƬɀƺȅǣȇƏȸɀƏȇƳٮוƫɵǔȒǼǼȒɯǣȇǕɀƬǣƺȇɎǣˡƬɀƺȅǣȇƏȸɀِ ǣȒȅƺƳǣƬƏǼ³ƬǣƺȇƬƺɀɎɖƳƺȇɎɀƏɎɎƺȇƳ ٮȸƺȵȒȸɎȒȇƬȒȇɎƺȇɎًɀƬǣƺȇɎǣˡƬƺɴƬƺǼǼƺȇƬƺƏȇƳɎȸƏƬǸȸƺƬȒȸƳɀȒǔɎǝƺȵȸƺɀƺȇɎƺȸɀِÁǝǣɀƬȒɖȸɀƺǝƏɀ׏׎ 30 students/year.

Python in biology for beginners

ٮɎǝȒɀƺɯǝȒȵȸȒǔƺɀٮ׎¨ǝ(ɀɎɖƳƺȇɎɀǣȇƫǣȒǼȒǕɵًȅƺƳǣƬƏǼƫǣȒǼȒǕɵًȅƺƳǣƬǣȇƺȒȸǔƏȸȅƏƬɵא׏ً!0 sionally connected to biology.

Course coordinator: Leonid Bystrykh

XȇɎȸȒƳɖƬɎǣȒȇƏȸɵƬȒɖȸɀƺȒȇȵɵɎǝȒȇǔȒȸƫǣȒǼȒǕǣɀɎɀًǣȇƬǼɖƳƺƫƏɀǣƬǕȸƏȅȅƏȸًȒȵƺȸƏɎǣȒȇɀɯǣɎǝˡǼƺɀً ɖɀƺȒǔɀɎƏɎǣɀɎǣƬƏǼǔɖȇƬɎǣȒȇɀًȅƏǸǣȇǕɀƬǣƺȇɎǣˡƬǣǼǼɖɀɎȸƏɎǣȒȇɀًƏȇƏǼɵɀǣȇǕǣȅƏǕƺɀِ

Objectives: Biologists are traditionally educated in programming-free environment. This causes serious limitations in the ability to collect, process and understand the data they create or use from others. Python is universal and relatively simple programming language, one of the most popular in science at this time. Among others, it contains biological packages. Re- gretfully, many biologists are not aware of this fact. Many python tutorials are based on exam- ples, which do not appeal to biology or medical students. In this course I make an adaptation of selected python packages for biological applications.

kȇȒɯǣȇǕɎǝǣɀǼƏȇǕɖƏǕƺɯǣǼǼǣȅȵȸȒɮƺɎǝƺƏƫǣǼǣɎɵȒǔɀɎɖƳƺȇɎɀɎȒȵȸȒƬƺɀɀًƏȇƏǼɵɿƺƏȇƳɖȇƳƺȸɀɎƏȇƳ their and other’s data. This is essential for proper development of the young scientists.

Genome data for beginners and advanced

׎J³x³¨ǝ(ɀɎɖƳƺȇɎɀ٢ǣȇƬǼɖƳǣȇǕ !z¨ǝ(ɀɎɖƳƺȇɎɀ٣א׏ً!0 Course coordinator: Leonid Bystrykh

Objectives: (ƏɎƏȸƺɎȸǣƺɮƏǼǔȸȒȅȵɖƫǼǣƬƳƏɎƏƫƏɀƺɀًɖɀƺȒǔ«ƏȇƳȵɵɎǝȒȇɀƬȸǣȵɎɀǔȒȸɎǝƺƏȇƏǼɵɀǣɀȒǔ data. Gene expression data processing for microarrays, bulk RNAseq data and single-cell RNA- seq

To increase the understanding of the basic principles of bioinformatics and to gain practical skills in bioinformatics analysis of sequence data.

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ERIBA | Annual Report V2.indd 52 16-07-2020 21:01 Python for biologists

ȒȸǕƏȇǣɿƺƳƏɎkƏȸȒǼǣȇɀǸƏXȇɀɎǣɎɖɎƺǣȇ³ɎȒƬǸǝȒǼȅً³ɯƺƳƺȇًח׎׏אxƏɵ

20 participants

ȸِnƺȒȇǣƳ ɵɀɎȸɵǸǝƏȇƳ(ȸِàǣƬɎȒȸJɖȸɵƺɮ)يȒȒȸƳǣȇƏɎȒȸɀ!

XȇɎȸȒƳɖƬɎǣȒȇƏȸɵƬȒɖȸɀƺȒȇȵɵɎǝȒȇǔȒȸƫǣȒǼȒǕǣɀɎɀًǣȇƬǼɖƳƺƫƏɀǣƬǕȸƏȅȅƏȸًȒȵƺȸƏɎǣȒȇɀɯǣɎǝˡǼƺɀً ɖɀƺȒǔɀɎƏɎǣɀɎǣƬƏǼǔɖȇƬɎǣȒȇɀًȅƏǸǣȇǕɀƬǣƺȇɎǣˡƬǣǼǼɖɀɎȸƏɎǣȒȇɀًƏȇƏǼɵɀǣȇǕǣȅƏǕƺɀِ

Genome biology

ȒȸǕƏȇǣɿƺƳƏɎkƏȸȒǼǣȇɀǸƏXȇɀɎǣɎɖɎƺǣȇ³ɎȒƬǸǝȒǼȅً³ɯƺƳƺȇًח׎׏א³ƺȵɎƺȅƫƺȸ

19 doctoral students

ȸِnƺȒȇǣƳ ɵɀɎȸɵǸǝƏȇƳ(ȸِàǣƬɎȒȸJɖȸɵƺɮ)يȒȒȸƳǣȇƏɎȒȸɀ!

ƏɎƏȸƺɎȸǣƺɮƏǼǔȸȒȅȵɖƫǼǣƬƳƏɎƏƫƏɀƺɀًɖɀƺȒǔ«ƏȇƳȵɵɎǝȒȇɀƬȸǣȵɎɀǔȒȸɎǝƺƏȇƏǼɵɀǣɀȒǔƳƏɎƏِJƺȇƺ) expression data processing for microarrays, bulk RNAseq data and single-cell RNAseq

To increase the understanding of the basic principles of bioinformatics and to gain practical skills in bioinformatics analysis of sequence data.

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ERIBA | Annual Report V2.indd 53 16-07-2020 21:01 Outreach and Dissemination

ERIBA is committed to outreach and dissemination activities. To this cause, ERIBA personnel consistently take part in various communica- tion and outreach activities. This is to ensure that general public is well aware of the research activities in ERIBA. Such activities also bring general public closer to research and generates a lot of enthusiasm in kids to become the scientists of tomorrow. ERIBA seeks to connect a wide range of audiences outside the academia: public in general, secondary education students, industry, decision-makers, media, and patient organisations. Public events, activities for schools, tours and many more initiatives are taken to achieve the goals.

Some of our most notable activities are listed below

Media

ƺƳǣɎǣȒȇِח׎׏אɀƏȸɎǣƬǼƺɯƏɀȵɖƫǼǣɀǝƺƳǣȇɎǝƺkǣǴǸ٢ȅƏǕƏɿǣȇƺ٣ǣȇɎǝƺxƏȸƬǝټàǣƬɎȒȸJɖȸɵƺɮ % ɯǝƺȸƺǝƺƳƺɀƬȸǣƫƺƳǝǣɀȸƺɀƺƏȸƬǝɯǝǣƬǝٺXȇƳƺƳȒȇǸƺȸƺǸȸȒƬǝɎƺȇɮƏȇ(zٹÁǝƺɎǣɎǼƺɯƏɀ ٢ƳƏȸǸ(z٣ِٺǝƏȸƳɎȒˡȇƳǕƺȇƺɀٹƏȸɎƫǣȒǣȇǔȒȸȅƏɎǣƬɀɎȒȒǼɀɎȒˡǕɖȸƺٮȒǔٮɖɀƺɀɀɎƏɎƺ

% Research from an international team, including Peter Lansdorp and Victor Guryev from ERIBA in Groningen, published in Nature communications made headlines in ukrant ٢ɯɯɯِɖǸȸƏȇɎِȇǼ٣ِÁǝƺɎƺƏȅƳǣɀƬȒɮƺȸƺƳɀɎȸɖƬɎɖȸƏǼƳǣǔǔƺȸƺȇƬƺɀǣȇɎǝƺ(zȒǔǣȇƳǣɮǣƳɖƏǼɀِ “Lansdorp’s technique single-cell strand seq technology) can view the entire chromo- some,” says Guryev. “In addition, you can distinguish between the chromosomes inher- ited from the father and from the mother, which is impossible with other techniques.”

% Gerald de Haan’s Interview was published in Volkskrant (https://www.volkskrant.nl/wetenschap/vreemd-medicijncocktail-maakt- ٣ƏƫȒɖɎȸƺǴɖɮƺȇƏɎǣȒȇȒǔƫǼȒȒƳِRƺȸƺًǝƺƳǣɀƬɖɀɀƺƳٖוהƏ׎דדƫƬۃǴȒȇǕƺȸٮƫǣȒǼȒǕǣɀƬǝٮȒɖƳƺȸƺȇ ɎǝƺǣȅȵȒȸɎƏȇƬƺƏȇƳƏɀɖȸȵȸǣɀƺˡȇƳǣȇǕƫɵȸƺɀƺƏȸƬǝƺȸɀȒǔƫȒȒɀɎǣȇǕɎǝƺǣȅȅɖȇƺɀɵɀɎƺȅ of individuals. This boost resulted in older becoming younger by two years.

Interview RTL Editie NL Interview Radio1: Verjonging van bloed

ɎǝƏȇȇǣɮƺȸɀƏȸɵȒǔɎǝƺÈȇǣɮƺȸɀǣɎɵȒǔJȸȒȇǣȇǕƺȇًƏȇד׎גƏɎɎǝƺȒƬƬƏɀǣȒȇȒǔɎǝƺًבȇhɖȇƺ׏ % honorary doctorate was awarded to professor Titia de Lange (Rockefeller University). Ti- ɎǣƏƳƺnƏȇǕƺǝƏɀȅƏƳƺɀƺȅǣȇƏǼƬȒȇɎȸǣƫɖɎǣȒȇɀǣȇɎǝƺˡƺǼƳȒǔƬƏȇƬƺȸƏȇƳƏǕƺǣȇǕƫǣȒǼȒǕɵِ ɎɮȵȸȒǕȸƏȅȅƺñȒȅƺȸǕƏɀɎƺȇ٣ɯǝƺȸƺɀǝƺ ³ǝƺɯƏɀǣȇɎƺȸɮǣƺɯƺƳƫɵhƏȇǣȇƺƫƫȸǣȇǕ٢ਫ talked about life, work, and science. Gerald de Haan acted as the honorary promotor.

% Judith Paridaen was elected as one of the members of Young Academy Groningen. It is a club for the University of Groningen’s most talented, enthusiastic and ambitious young researchers. A video with Judith describing her stem cell research was posted on youtube (https://www.youtube.com/ ñx٣ƫɵɎǝƺÈȇǣɮƺȸɀǣɎɵȒǔJȸȒȇǣȇǕƺȇהxÁǕבɴRàƺڻɯƏɎƬǝّɮ

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ERIBA | Annual Report V2.indd 54 16-07-2020 21:01 Events /Activities

Career Day

Members Involved: hɖƳǣɎǝ¨ƏȸǣƳƏƺȇًkƏɎɵƏ(ɮȒȸǣƏȇǣȇȒɮƏًȇǣɎƏ¨ȸƏɀًxƺǕǝƏÈȵƏƳǝɵƏɵً³ɵǼɮǣƏRȒǸɀ

׎ȵƺȒȵǼƺƏɎɎƺȇƳƺƳɎǝƺƺɮƺȇɎِוȵȵȸȒɴِח׎׏אɎǝגאƏȸƺƺȸ(ƏɵɯƏɀȒȸǕƏȇǣɀƺƳȒȇɎǝƺȵȸǣǼ! The event featured presentations from people from various disciplines. The speakers shared their experience and provided advice to students on careers outside academia. Mate Palfy ȒȅȅɖȇǣɎɵxƏȇƏǕƺȸ¨ȸƺǼǣǕǝɎɀًǣȇǣɎǣɎƏɎǣɮƺȒǔÁǝƺƬȒȅȵƏȇɵȒǔ ǣȒǼȒǕǣɀɎɀً!ƏȅƫȸǣƳǕƺًÈkً! hȒȒkȒȒ(ǣɀƬȒɮƺȸɵ³ƬǣƺȇɎǣɀɎhƏȇɀɀƺȇȵǝƏȸȅƏƬƺɖɎǣƬƏǼƬȒȅȵƏȇɵً ƺǼǕǣɖȅًMaximeٮ³ƺȒȇǕ ƏȇƳ ɖɀǣȇƺɀɀ(ƺɮƺǼȒȵƺȸǔȒȸXȇɮƺȸɎÁȒɴًJǝƺȇɎًPaula vanټȸȒƺǔٍ¨ٻWillemsIȒɖȇƳƺȸȒǔIȒȒƳǼƏƫ Tijn Institute Manager AMOLF, Amsterdam, Marnix Wieffer³ƺȇǣȒȸxƏȸǸƺɎǣȇǕxƏȇƏǕƺȸ(ȸɖǕ Safety at Elsevier, The Netherlands, Annemieke van der Goot Consultant at Vindsubsidies (Idox Grants BV), The Netherlands, Eva Teuling Education Coordinator at the University of Gronin- gen, Groningen. The event was a huge success and will again be held in 2021.

Zpannend Zernike

Staff members involved: Organiser: Anton Steen hɖƳǣɎǝ¨ƏȸǣƳƏƺȇًkƏɎɵƏ(ɮȒȸǣƏȇǣȇȒɮƏًnǣƺɀƫƺɎǝàƺƺȇǝȒǔǔًxƏȸǣǴƺ³ƺȅȅƺǼǣȇǸً³ɵǼɮǣƏيàȒǼɖȇɎƺƺȸɀ RȒǸɀًǼǣƳƏƳƺRƏƏȇًnƺƺȇhƏȇɀɀƺȇً³ƏƫȸǣȇƏhƏƬȒƫɀً(ƏȇǣƺǼǼƺnɖǣȇƺȇƫɖȸǕًxƺǕǝƏÈȵƏƳǝɵƏɵً Jacob Wudarski, Gloria Casas Gimeno.

ERIBA is committed to public outreach activities and wants to create public awareness on ɀƬǣƺȇɎǣˡƬȸƺɀƺƏȸƬǝًǣȇɀȵǣȸƺɀƬǣƺȇɎǣɀɎɀȒǔɎȒȅȒȸȸȒɯِÁǝƺ“Weekend van de Wetenschap” locally known as ñȵƏȇȇƺȇƳñƺȸȇǣǸƺ is an event in which research institutes, the University of Gron- ingen, the UMCG, and the Hanze Hogeschool team up in Groningen as a single organization ٮȒȸǕƏȇǣɿǣȇǕɀƬǣƺȇɎǣˡƬƏƬɎǣɮǣɎǣƺɀǔȒȸȵȸǣȅƏȸɵɀƬǝȒȒǼƬǝǣǼƳȸƺȇƏȇƳɎǝƺǣȸǔƏȅǣǼǣƺɀِ0«X ƏǼɀȒȵƏȸɎǣƬ ח׎׏אƬɎȒƫƺȸً ɎǝȒǔדȇ³ƏɎɖȸƳƏɵًɎǝƺ ǣȵƏɎƺƳǣȇɎǝǣɀƺɮƺȇɎƏȇƳȒȵƺȇƺƳǣɎɀƳȒȒȸɀɎȒɎǝƺȵɖƫǼǣƬِ ׎ȵƺȒȵǼƺɮǣɀǣɎƺƳɎǝƺ0«X ȵȸƺȅǣɀƺɀƏȇƳɎȒȒǸȵƏȸɎǣȇɮƏȸǣȒɖɀɀƬǣƺȇɎǣˡƬƏƬɎǣɮǣɎǣƺɀِזהȅȒȸƺɎǝƏȇ ٮÁǝƺƏƬɎǣɮǣɎǣƺɀǣȇƬǼɖƳƺƳǣɀȒǼƏɎǣȒȇȒǔ(zًƺɴȵǼȒȸǣȇǕȅȒƳƺǼȒȸǕƏȇǣɀȅɀɖɀƺƳǔȒȸɀƬǣƺȇɎǣˡƬȸƺ ٮɀƺƏȸƬǝًRƺƏǼɎǝɵƏǕƺǣȇǕȷɖǣɿًƏɀƬǣƺȇɎǣˡƬƺɀƬƏȵƺȸȒȒȅًƏȇƳƳǣɮǣȇǕǣȇƳƏɎƺɀɀƺɀɀǣȒȇِÁǝƺɀƺƏƬɎǣɮǣ ties generated a lot of enthusiasm and enlightened the public on the importance of science ƏȇƳɀƬǣƺȇɎǣˡƬȸƺɀƺƏȸƬǝً

3rd Molecular Biology of Ageing Meeting

Members involved: JƺȸƏǼƳƳƺRƏƏȇً!Ȓȸ!ƏǼǸǝȒɮƺȇًnǣƺɀƫƺɎǝàƺƺȇǝȒǔǔًxƺǕǝƏÈȵƏƳǝɵƏɵًzǣȇƏkȒȒǼً³ɵǼɮǣƏRȒǸɀً ٮRƏɀɀǣȇǕًǼǣƳƏƳƺRƏƏȇًkƺɮǣȇRɖǣɿǣȇǕƏً0ǼƺȇǣIǣɎɀǣȒɖًJƺȸɎȸɖƳkȒȸɎȅƏȇًJǼȒȸǣƏ!ƏٮȇȇƺɎàȒɀ ³ɿɖƬɀً(ƏȇǣƺǼǼƺnɖǣȇƺȇƫɖȸǕًٮɀƏɀJǣȅƺȇȒً0ȇǣǸȒIƺǸƺɎƺ

ERIBA successfully organized for the third time the Molecular Biology of Ageing (www.bioageing.nl) Meeting, focusing on ageing research. The meeting was held from Oc- tober 10-12, 2019, at the University Medical Center Groningen. The organizing committee brought together world-leading scientists to discuss the diverse research areas that are rel- evant for understanding the biology of ageing. To ‘build the scientists of tomorrow’ the ‘meet ɀƺɀɀǣȒȇɯƏɀƏǼɀȒȒȸǕƏȇǣɿƺƳɯǝƺȸƺ¨ǝ(ɀɎɖƳƺȇɎɀƏȇƳɵȒɖȇǕɀƬǣƺȇɎǣɀɎɀǣȇɎƺȸƏƬɎƺƳټɎǝƺƺɴȵƺȸɎ with the experts to gain knowledge from their experiences.

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ERIBA | Annual Report V2.indd 55 16-07-2020 21:01 Science activities and visits

 X ɀƬǣƺȇɎǣɀɎhɖƳǣɎǝ¨ƏȸǣƳƏƺȇƏȇƳǝƺȸǼƏƫȅƺȅƫƺȸɀkƏɎɵƏ(ɮȒȸǣƏȇǣȇȒɮƏً»0 • Glòria Casas Gimeno, Nynke Oosterhof represented the institute in Science Fair ‘University of Noorderzon’ organized by the Young Academy Groningen. They ǝƏƳƏȇƺɴǝǣƫǣɎȒȇ(zƏɎɎǝƺƺɮƺȇɎِ 

• Anton Steen, a member of Liesbeth Veenhoff’s group also represented the institute at the event. He, in cooperation with Healthy Ageing Network Northern Netherlands (HANNN), organised Escape room, crack the code of happiness.

• Michael Chang presented about “model organisms in ageing research” at the Sum merschool Healthy Ageing.

• Liesbeth Veenhoff hosted professionals (directors and managers) from the public and private sectors following the 'Comenius Leergang' at ERIBA.

• Floris Foijer shared his expertise on CRISPR and aneuploidy to ex UMCG employees. He also organised and offered a tour on single cell sequencing for Care4BrittleBones. ٮƳƳǣɎǣȒȇƏǼǼɵًǝƺƏǼɀȒȵȸƺɀƺȇɎƺƳƏɎƏȇƺɮƺȇɎȒȸǕƏȇǣɀƺƳ!ǝƺȅǣɀƬǝƺkȸǣȇǕJȸȒȇǣȇǕƺȇ  k!zàِ

ɀټɎɎǝƺ¨ǣȇɎȒǔ³ƬǣƺȇƬƺƺɮƺȇɎǝƺǼƳǣȇJȸȒȇǣȇǕƺȇhƏɀǸƏȸƺȇkȒǝǼǣ٢Ə¨ȒɀɎƳȒƬǣȇ(ƺȅƏȸǣƏ • ɀǼƏƫ٣ǝƺǼȵƺƳȒȸǕƏȇǣɿƺɎǝƺټǝ(ɀɎɖƳƺȇɎǣȇ0ǼǼƺȇzȒǼǼƺȇ¨ǕȸȒɖȵ٣ƏȇƳxƏȇƳɵkȒȒȵȅƏȇ٢  event and also gave a seminar on their research. Floris Foijer also participated and pre sented in this event.

• Judith Paridaen was the Invited spreaker at Science Cafe Nijmegen "Genregulatie, het algoritme van het leven"

ɀǼƏƫȒȸǕƏȇǣɀƺƳƏɯȒȸǸɮǣɀǣɎǔȒȸǝǣǕǝټkƏɎɵƏ(ɮȒȸǣƏȇǣȇȒɮƏًƏȅƺȅƫƺȸǣȇhɖƳǣɎǝ¨ƏȸǣƳƏƺȇ • school students Willem Lodewijk Gymnasium Wetenschapstweedaagse”.

• Leen Janssen and Renee Seinstra from Ellen Nollen’s lab helped organise an activity for "student for a day" orientation event by University of Groningen.

ח׎׏א׎ÁÈ(ƺǼǔɎɀɎɖƳƺȇɎɀǔȒȸƏǼƏƫɎȒɖȸȒȇxƏɵ׏׎ɎǝבX ǝȒɀɎƺƳ»0 •

Science in a Box

Leading Staff member: Stijn Mouton

ɯƺȸƺٺƺǕƺȇƺȸƏɎǣȒȇ Ȓɴƺɀ»ٹɯƏɀȒǔˡƬǣƏǼǼɵǼƏɖȇƬǝƺƳًƏȇƳɎǝƺˡȸɀɎٺ³ƬǣƺȇƬƺǣȇƏ Ȓɴٹًח׎׏אXȇ sold. These Boxes provide a hands-on experience to explore topics as regeneration and stem cells in the class room. More information can be found on our website: scienceinabox.nl

-ɖȸǣȇǕƏɖɎɖȅȇًɯƺɀɎƏȸɎƺƳȒɖȸȒȇǼǣȇƺȵȸȒȅȒɎǣȒȇɯǝǣƬǝǣȇƬǼɖƳƺƳƏɀǝȒȸɎɮǣƳƺȒǣȇɎȸȒƳɖƬ) ing the concept. This video was actively shared on several online channels of ERIBA and the UMCG, and received a high number of views. In addition, interviews about the development of ɯƺȸƺǕǣɮƺȇǔȒȸ¨ȒǼɀɀǼƏǕƏȇƳkƺȇȇǣɀǣȇɿǣƬǝɎِٺ³ƬǣƺȇƬƺǣȇƏ Ȓɴٹ

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ERIBA | Annual Report V2.indd 56 16-07-2020 21:01 57

ERIBA | Annual Report V2.indd 57 16-07-2020 21:01 5EKGNěKĂE Advisory Board

Christine Mummery

¨ȸȒǔƺɀɀȒȸȒǔ(ƺɮƺǼȒȵȅƺȇɎƏǼ ǣȒǼȒǕɵ !ǝƏǣȸȒǔɎǝƺ(ƺȵƏȸɎȅƺȇɎȒǔȇƏɎȒȅɵƏȇƳ0ȅƫȸɵȒǼȒǕɵ Leiden University Medical Center

The Netherlands

Johan Auwerx

Professor and Nestlé Chair in Energy Metabolism

Ecole Polytechnique Fédérale in Lausanne

Switzerland

Helle Ulrich

³ƬǣƺȇɎǣˡƬ(ǣȸƺƬɎȒȸȒǔɎǝƺXȇɀɎǣɎɖɎƺȒǔxȒǼƺƬɖǼƏȸ ǣȒǼȒǕɵ Professor at the Faculty of Biology

University of Mainz

Germany

Yves Barral

Associate Professor of Biochemistry

(ƺȵƏȸɎȅƺȇɎȒǔ ǣȒǼȒǕɵ

0ÁRñɖȸǣƬǝ Switzerland

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ERIBA | Annual Report V2.indd 58 16-07-2020 21:01 Sponsors

The European Institute for the Biology of Ageing is made possible by:

Ministry of Economic Affairs, Agriculture and Innovation

The Province of Groningen

Collaboration of the Northern Netherlands (SNN)

The European Union

The Noaber Foundation

The Pediatric Oncology Foundation Gronin- gen (SKOG)

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ERIBA | Annual Report V2.indd 59 16-07-2020 21:01 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

Postal 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

ERIBA | Cover .indd Alle pagina's 30-06-2020 13:49