International Summer School of H2020-TWINN-2015

WIDENLIFE project (Grant No 692065) and SEARMET project (Grant No 692299)

Single-cell and low-input methodologies in reproductive biology , , June 13-14, 2017 Venue: Institute of Molecular and Cell Biology, , Omicum building, Riia 23b/2, auditorium 105

Funded by the European Union through the Coordination and Support Action of the H2020 programme under grant agreement No 692065 „Widening the Scientific Excellence for Studies on Women’s and Fetal Health and Wellbeing“, No 692299 "Scientific Excellence in Animal Reproductive Medicine and Embryo Technology" and European Regional Development Fund through University of Tartu ASTRA project PER ASPERA

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PROGRAMME Tuesday, June 13, 2017 10:30-11:00 Welcome coffee 11:00 Opening words, Professor Ants Kurg, University of Tartu and Professor Ülle Jaakma, Estonian University of Life Sciences

I session: 11:10-11:55 Ann Van Soom, PhD, Ghent University, Belgium “Emerging role of extracellular vesicles in communication of preimplantation embryos in vitro“ 11:55-12:40 Martin Anger, PhD, CEITEC, Czech Republic “Challenges of chromosome segregation in oocytes and early embryos in mammals” 12:40-14:00 Lunch break

II session: 14:00-14:45 Jennifer Southcombe, PhD, and Ingrid Granne, PhD, University of Oxford, United Kingdom “Paternal and maternal immunological factors in the peri-implantation endometrium”

14:45-15:30 Mariann Koel, MSc, University of Tartu, Estonia “The interactome of human embryo implantation” 15:30-16:00 Coffee break

III session: 16:00-16:45 Nathalie Brison, PhD, University of Leuven, Belgium

„Non-invasive prenatal testing: clinical and biological challenges“ 16:45-17:30 Eftychia Dimitriadou, PhD, University of Leuven, Belgium

“Genome-wide approaches for preimplantation genetic diagnosis and screening”

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Wednesday, June 14, 2017 09:30-10:00 Welcome coffee

IV session: 10:00-10:45 Joris Vermeesch, PhD, University of Leuven, Belgium

“The embryo is the cradle of chromosomal disorders, chimaerism and mixoploidy” 10:45-11:30 Olga Tšuiko, MSc, University of Tartu, Estonia

“Unravelling chromosomal instability in mammalian preimplantation embryos" 11:30-12:15 Ene Reimann, PhD, University of Tartu, Monika Nõmm, Estonian University of Life Sciences, Estonia “Bovine embryo genomics using NGS” 12:15-14:00 Lunch break

V session: 14:00-14:45 Jan Ole Bertelsen Secher, PhD, University of Copenhagen, Denmark

“In vivo testing of porcine iPSC” 14:45-15:30 Björn Heindryckx, PhD, Ghent University Hospital, Ghent University, Belgium

“In vitro generated gametes from stem cells: to be or not to be” 15:30-16:00 Coffee break

16:00-16:45 Mait Metspalu, PhD, , Estonia

“Reconstructing population histories from genetic diversity patterns” Closing remarks

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Speakers Joris Vermeesch University of Leuven, Belgium Title of the talk "The embryo is the cradle of chromosomal disorders, chimaerism and mixoploidy" Joris R. Vermeesch, Ph.D. Ir, is heading the department of human genetics, is professor Molecular Cytogenetics and genome research. He is heading the Constitutional Cytogenetics unit of the Center of Human Genetics, and coordinating the genomic core. Before taking up his current position, he was head of the genomics unit in the basic research division of Aventis CropScience and responsible for large scale genome analyses in several crops. The laboratory of molecular cytogenetics and genome research has been pioneering in array development and implementation and is currently developing methods for massive parallel sequencing applications in preimplantation, prenatal and postnatal diagnosis with a focus on structural variation detection. Second, the group is responsible for the cytogenetic diagnostic services of the Center for Human Genetics. Starting from clinical samples, the laboratory aims to understand the mechanisms underlying chromosomal instability and rearrangements. It actively developed methods for single cell CNV detection and will continue to address outstanding questions about instability using single cell genomic approaches. Third, the laboratory actively seeks to define the molecular causes of developmental, mental and behavioural disturbances. The group is partner of the SymbioSys, the systems biology center of excellence in computational biology. Joris Vermeesch has published over 250 papers with an H-index 42.

Ann Van Soom Ghent University, Belgium Title of the talk “Emerging role of extracellular vesicles in communication of preimplantation embryos in vitro“ Ann Van Soom graduated in 1988 as DVM at the faculty of Veterinary Medicine, Ghent University, Belgium, and obtained a PhD on the development of bovine embryos in 1996. She has been employed at Ghent university since 1990. At present, she holds a position as full professor at the department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, and is also Head of Department. She has been teaching assisted reproduction in domestic species, small animal reproduction and obstetrics to the veterinary students for almost 20 years now. She is a diplomat of the European College of Animal Reproduction (ECAR) since 1999, and has been a member of the EVSSAR and the IETS for many years. She has been elected as a governor for IETS in 2007 and in 2013. She was member and Chair of the HASAC (Health and Safety Advisory Committee) Research subcommittee of IETS for about ten years. She was chair of the COST Action Epiconcept FA1201 from 2012-2016, and is a member of the EU-

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ITN network RepBiotech. She is also serving in national and international advisory commmittees on sanitary risks involved with assisted reproduction in domestic species, and has been authoring a chapter in the 4th edition of the IETS Manual dealing with these problems. She is supervising a group of about 10 PhD students and three postdocs working together on embryonic development and semen quality in different model species, like horses, cattle, cats, dogs and pigs. She has published more than 200 peer reviewed papers listed in WoS, h-index =37. Her clinical activities are related to small animal reproduction, with an emphasis on semen collection, gamete cryopreservation and artificial insemination in cats and dogs. She is also visiting catteries and dog breeding facilities which are experiencing breeding problems. She is offering advice for applying new methods of contraception and oestrus induction in dogs and cats to practicing veterinarians, as well as giving advice in small animal obstetrics.

Björn Heindryckx

Ghent University, Belgium Title of the talk “In vitro generated gametes from stem cells: to be or not to be” Principle Investigator, Ghent-Fertility and Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Ghent, BELGIUM. Professor at Ghent University. PhD in Medical Sciences in 2006: “Experimental contribution to infertility research: Artificial gametes and assisted oocyte activation”. Currently promoter/co-promoter of 9 PhD students. Coordinator of Special Interest Group of Stem Cells of ESHRE / Co-founder of the Belgian Society for Stem Cell Research (BeSSCR)/ Board Member of the Belgian Society for Reproductive Medicine. Author and co-author of 67 A1 publications. Main topics of research: Early lineage segregation in mouse and human / mouse and human somatic cell nuclear transfer / Mouse and human embryonic stem cell derivation / Investigating different states of stem cell pluripotency in mouse and human / Differentiation of pluripotent stem cells into germ cells / Failed fertilisation after ICSI & the oocyte activation mechanism / Oocyte maturation arrest / Nuclear Transfer techniques to overcome mitochondrial disease transmission / Non-invasive techniques of gamete & embryo selection / Pre-implantation genetic diagnosis and screening using next generation sequencing.

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Ene Reimann University of Tartu, Estonia Title of the talk “Bovine embryo genomics using NGS” I started studying gene technology in University of Tartu in 2002, where my first study subject was fis gene promoter area of Pseudomonas putida under supervision of dr. Riho Teras and professor Maia Kivisaar in Chair of Genetics. For making my masters degree I moved to the department of Physiology. Under supervision of professor Sulev Kõks and professor Külli Kingo I studied vitiligo and its association with pro-inflammatory cytokines – interleukin 10 family cytokines and their receptors. I continued studying vitiligo during my doctoral studies, where in addition to cytokines, I focused on cutaneous neuroendocrine system and its role in vitiligo pathogenesis. After finishing my PhD in neuroscience in 2012 I continued working with professor Sulev Kõks – I became a research fellow of pathophysiology and also the head of the core facility of clinical genomics. I have participated in different projects in collaboration with Tartu University Hospital. We have studied i.e. vitiligo, psoriasis, Parkinson’s disease, different bone and muscle diseases, cardiovascular system. Between 2009 and 2016 I also worked as a researcher of genomics in Department of Reproductive Biology at the Estonian University of Life Sciences – our projects there were associated mostly with cattle and their reproductive health. My main competency in these projects was the next generation sequencing – whole genome, whole exome and whole transcriptome sequencing. Since February 2017 I am working as a research fellow of clinical genomics and personalized medicine under supervision of professor Alireza Fazeli. My main study object is psoriasis and its biomarkers for clinical diagnostics and treatment strategies.

Monika Nõmm Estonian University of Life Sciences Title of the talk “Bovine embryo genomics using NGS” Monika Nõmm is a Junior Research Fellow and PhD student in the department of reproductive biology at the Estonian University of Life Sciences. She specializes in bovine in vitro fertilization and has also experience as an European project manager. Her PhD topic is related to in vitro production of dairy cattle embryos.

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Martin Anger CEITEC, Czech Republic Title of the talk “Challenges of chromosome segregation in oocytes and early embryos in mammals” Dr. Martin Anger received his PhD from Academy of Sciences of the Czech Republic in 2001. For his postdoctoral studies he initially joined laboratory of professor Richard Schultz at Department of Biology, University of Pennsylvania, USA and after four years moved to The Research Institute of Molecular Pathology in Vienna, joining laboratory of professor Kim Nasmyth. With this team he then moved to University of Oxford, UK, where he conducted his research for 3 years. After return to the Czech Republic in 2008 he received prestigious Installation grant form European Molecular Biology Organization and Marie Curie reintegration grant and established his laboratory at Academy of Sciences of the Czech Republic. In 2011 his group joined Central European Institute of Technology (CEITEC) in Brno (http://www.ceitec.eu/ceitec- vri/mammalianreproduction/rg28) where he became a director of CEITEC – Veterinary research Institute unit at the beginning of 2015. His research interests involve regulation of cell cycle, meiosis, mitosis, early embryonic development and regulation of chromosome segregation.

Mait Metspalu Estonian Biocentre, Estonia Title of the talk “Reconstructing population histories from genetic diversity patterns” I studied geography and molecular biology and evolution at the University of Tartu where I also did my PhD on phylogeography of human mtDNA in South Asia in 2006. I became the vice-director (2010) and subsequently the director (2014) of the Estonian Biocentre (EBC), Tartu, Estonia. The EBC is the leading research institute in Estonia in the interdisciplinary and interconnected fields of evolutionary genomics, population genetics and archaeogenetics. I spent one year as a visiting research fellow in UC Berkeley in 2012-2013. My research concentrates on using and developing population genetics approaches to understand the genesis of the genetic diversity patterns of humans through reconstructions of past population movements, splits and admixtures as well as adaptations to local environments (both natural and manmade). We operate a large sample bank consisting of over 20 000 samples from all over the globe of which ca 4000 have been genotyped (genome-wide arrays) and for over 400 we have obtained high coverage full genome sequences. During the few past years we have also started a dedicated ancient DNA program aiming mostly at reconstructing population changes in the East European Plain since the Paleolithic.

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Jan Ole Bertelsen Secher University of Copenhagen, Denmark Title of the talk “In vivo testing of porcine iPSC” I am a DVM and have worked in clinical practice for 4 years after finishing my master. During my PhD my main interest was within in vitro fertilization, early embryology and pluripotent stem cells. I have worked with porcine oocyte activation and manipulation of early embryos. One of the publications from my PhD was on 3D imaging of porcine blastocysts. At the moment I am working with bovine IVF and genomic and transcriptomic analysis of the embryos.

Olga Tšuiko University of Tartu, Estonia Title of the talk “Unravelling chromosomal instability in mammalian preimplantation embryos" I obtained bachelor’s degree in gene technology and master’s degree in biomedicine at the University of Tartu. Since 2012 I am doing my doctoral studies at the Faculty of Medicine in the field of reproductive biology and medicine under the supervision of prof. Andres Salumets and prof. Ants Kurg. In 2014 I was seconded to Belgium for two years, where I joined the group of prof. Joris Versmeech at KU Leuven to study chromosomal instability in cleavage-stage embryos using bovine as an animal model. Since 2016, I work at the Competence Centre on Health Technologies in Tartu, where I continue my research on early embryogenesis with specific focus on factors determining embryonic developmental potential. Additionally, I am involved in establishing preimplantation genetic screening (PGS) in Estonia.

Mariann Koel University of Tartu, Estonia Title of the talk “The interactome of human embryo implantation” I obtained my MSc in Cell Biology from the University of Tartu (cum laude, 2013). Thereafter I spent 6 months in the University of Helsinki in the Department of Obstetrics and Gynecology, where I worked in Juha Tapanainen’s workgroup on differentiating trophoblast cells from human embryonic stem cell line. In 2014, I started my PhD studies in the University of Tartu under the supervision of Viljar Jaks and prof. Andres Salumets. In 2016 I was seconded in Karolinska Institutet in Sweden, where I joined the group of prof. Juha Kere in the framework of SARM project. Since 2012 I am working as a researcher in Competence

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Centre on Health Technologies in Estonia. My research interests are related to endometrium receptivity, embryo implantation and early trophoblast differentiation.

Eftychia Dimitriadou

University of Leuven, Belgium Title of the talk "Genome-wide approaches for preimplantation genetic diagnosis and screening" Dr Eftychia Dimitriadou studied biotechnology in the University of Ioannina, Greece, where she consequently got specialized in genetics of human infertility. Shortly after completing her PhD on Chromosomal aberrations, epigenetic factors and retrotransposition mechanisms in 2012, she joined the Laboratory for Cytogenetics and Genome Research, KU Leuven, Belgium. As a postdoctoral researcher she focused on the study of chromosomal instability in humans and on the development, validation and implementation of novel methods for preimplantation genetic diagnosis. She has participated in severalresearch projects in collaboration with national and international, academic and industrial partners working on reproductive genetics. Currently, she is a clinical laboratory geneticist in the Laboratory for Constitutional Cytogenetics in the Centre for Human Genetics, UZ Leuven, Belgium and is responsible for the development and clinical implementation of new methods for preimplantation and prenatal genetic screening and diagnosis.

Nathalie Brison University of Leuven, Belgium Title of the talk "Non-invasive prenatal testing: clinical and biological challenges" Dr. Brison graduated in Biomedical Sciences at the Catholic University of Leuven (KU Leuven, Leuven, Belgium) in 2005 and earned a Master’s degree in Molecular Medical Biotechnology in Ghent (Belgium). From 2006-2011, she obtained a PhD at the KU Leuven entitled ‘The HOX redux - Molecular Characterization of HOXD13 function during Limb Development and Disease’. In 2012, she studied the genetic causes of Autism Spectrum Disorders in the laboratory for Clinical Epidemiology (Centre for Human Genetics, University hospital, Leuven). In 2013, Dr. Brison joined the team of the Clinical Cytogenetics lab and was involved in the development of methods for non-invasive detection of fetal chromosomal aneuploidies by analysis of cell-free fetal DNA in the maternal circulation (NIPT). She supported the implementation, validation and accreditation of a new, high throughput analysis pipeline for NIPT. For her research on this field, Dr. Brison has been awarded the ‘Vienna Medical Academy Award’ at the European

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Society of Human Genetics (ESHG) conference in June, 2014 and an award for her presentation at the Belgian Society for Human Genetics (BeSHG) in February 2016. Dr. Brison is currently working as a clinical laboratory geneticist in the Laboratory for Constitutional Cytogenetics in the Centre for Human Genetics, University Hospital of Leuven (Belgium). She is responsible for the clinical implementation, optimization and quality control of Non-Invasive Prenatal Testing (NIPT) in routine prenatal diagnostics and is in training to become a certified laboratory supervisor for pre- and postnatal genetic testing.

Jennifer Southcombe University of Oxford, UK Title of the talk "Paternal and maternal immunological factors in the peri- implantation endometrium” I am a reproductive immunologist working in the Nuffield Department of Obstetrics and Gynaecology in the University of Oxford, aiming to further understand the nature of uterine immunity pre-pregnancy and immunological events that unfold in early pregnancy. My research specifically focuses on endometrial immune cells in recurrent miscarriage and paternal and maternal factors that influence endometrial cells.

Ingrid Granne University of Oxford, UK Title of the talk "Paternal and maternal immunological factors in the peri- implantation endometrium” Dr Ingrid Granne is a principle investigator in the Nuffield Department of Obstetrics and Gynaecology in the University of Oxford and Honorary Consultant Gynaecologist and Sub-Specialist in Reproductive Medicine and Surgery. She is the lead for the Recurrent Miscarriage and Early Pregnancy at Oxford University Hospitals NHS Trust. Research stems from this clinical interest, key themes are to understand endometrial factors in recurrent miscarriage and sub-fertility, the interactions between extracellular vesicles in early reproductive processes and understanding the impact of pregnancy on long-term health.

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„The Kissing Students“ sculpture and fountain in Tartu Town Hall Square

Thank you for participating in the Summer School “Single-cell and low- input methodologies in reproductive biology” and see you next time!