Epigenetics and Anticipation – Hanse-Wissenschaftskolleg Institute for Advanced Study & The antÉ Institute for Research in Anticipatory Systems

Epigenetics and Anticipation

Future gene expression and the possible future that drives anticipatory processes define the subject of the meeting. Hosted by the Hanse Institute for Advanced Studies (Delmenhorst, Germany), this international conference will bring together leading researchers in epigenetics and scholars active in explaining the various aspects through which anticipation is expressed.

Among the subjects of interest are those connected to Waddington’s attempt to describe the dynamics of interaction between genotype and phenotype. We are now almost 80 years past the beginning, and epigenetics has evolved to the point of integrating knowledge of changes informed by external factors of all kinds that affect gene activity and gene expression.

Conference participants will discuss aspects of transgenerational exposure (environment, diet, lifestyle, etc.), genetic diversification resulting from endogenous agents, and, more important, the nature of epigenetic information. Anticipatory processes (i.e., future possibilities that affect a current state) undergirding epigenetics will be of immediate interest.

The significance of examining epigenetics together with anticipatory processes derives from practical consequences. Informed by progress in epigenetics research and by the awareness of anticipatory processes underlying life, the scientific community addresses difficult medical problems (e.g., cancer treatment, spectrum disorders, aging, metabolism, etc., etc.) in new ways. This holds true as well for those preoccupied with the long-term consequences of technologies that change behavior patterns.

Furthermore, the making and remaking of the human being under circumstances of fast change pose challenges that should not be ignored as the human being defines its role in the future of the world. From the transgenerational persistence of less than desirable consequences (such as justifying intolerance and promoting hate) to cultural and “soft” inheritance of systems that promote compassion and solidarity, there is much to cover from the perspective of recent advances in epigenetic research. Anticipatory processes underlying these developments are often associated with epigenetic aspects. Consequently, it is of interest to see how molecular biologists and those who study current developments in various cultures communicate and benefit from each other’s expertise.

In order to design a meaningful conference program, we rely on a network of experts able and willing to help in identifying the most promising research-in-progress and the most advanced exchange of ideas. The intention is to bring together, in Delmenhorst, in 2021 (at a date acceptable to all) around 30-35 participants—from hard-core epigenetic scientists to those building upon epigenetic knowledge in formulating new perspectives—i.e., possible futures—concerning education, medical care, political action—more broadly, a framework for a nurturing culture or even several cultures. Presentations will be peer-reviewed. A volume, “Epigenetics and Anticipation” (tentative title) will be published in the Springer series “Cognitive Systems Monographs.”

Participation in the conference is by invitation only. Travel expenses and local accommodations will be covered.

Once the list of participants is finalized, a program will be structured and posted on the world-wide web. (Programs of past conferences can be retrieved at www.nadin.ws/ante-study). Presentations should be ready by the beginning of 2021 (formatting instructions to be provided).

Stefan Beck
Professor, Medical Genomics
Leader, Medical Genomics Research Group
University College London
Getting up close and personal with epigenetics in health and disease

There is growing consensus among researchers, clinicians, politicians, and the public that omics in one form or another will transform biomedical research, healthcare, and lifestyle decisions. For this transformation to happen and be successful, our knowledge of omics, including epigenomics, will need to advance to a level where it can safely and effectively inform Genomic Medicine in order to improve patient treatment and public health in general. I will discuss concepts and methods of how to identify epigenetic variants, how to infer their function, and how to proof their causality in health and disease. Furthermore, I will discuss current barriers in respect to the governance of sharing and reporting of epigenetic variants and explore innovative solutions in the context of the Personal Genome Project UK.

Stephan Beck received his PhD in 1985 from Konstanz University, where he studied DNA structure. After appointments at the MRC-LMB in Cambridge, Millipore Corporation in Boston, and the ICRF in London, he joined the Wellcome Trust Sanger Institute in 1996. During his tenure as Head of Human Sequencing, he played a leading role in the sequencing and analysis of the human genome. His current research focuses on the genomics and epigenomics of phenotypic plasticity in health and disease to advance translational, regenerative and personalized medicine.

Russell Bonduriansky
Professor, Evolutionary Biology
University of New South Wales
Nongenetic hereditary processes in the development of genetics and evolutionary biology

I will talk about the development of heredity theory since the 19th century, focusing on the role of nongenetic hereditary processes (“nongenetic inheritance”) and the reasons and consequences of its eventual exclusion from mainstream biological and medical research. I will also discuss recent evidence of nongenetic inheritance, and efforts to incorporate these phenomena into evolutionary theory.
Professor Bonduriansky obtained his doctoral degree at the University of Toronto in 2004. He is a member of the Evolution & Ecology Research Centre at UNSW. His research interests include: the role of environmental factors (especially diet) in development; nongenetic inheritance and its role in evolution; the evolution of ageing; the coevolution of the sexes. His main research focuses on understanding the role of environmental variation in shaping phenotypes within and across generations, and the implications of such effects for the evolution of life histories and reproductive traits.

Charlotte A.M. Cecil
Group Leader, Biological Psychopathology within the Generation R Study
Erasmus Medical Centre
Rotterdam, The Netherlands
Child mental health through the lens of epigenetics

Epigenetic processes have recently emerged as a potential mechanism through which genetic and environmental influences jointly shape children’s development, behaviour and disease risk, including the risk of psychiatric disorders. In this talk, I will discuss how the use of population-based birth cohorts is beginning to provide key insights into the relationship between epigenetics and mental health across development, with potentially widespread implications for the way that we understand, assess and perhaps in future even treat psychiatric disorders.

Dr Cecil is Assistant Professor at the Departments of Child & Adolescence Psychiatry and Epidemiology, Erasmus Medical Centre, and Group Leader of Biological Psychopathology within the Generation R Study—a large, prospective birth cohort of nearly 10,000 children followed from pregnancy to adolescence. She coordinates research examining the biological mechanisms through which genetic and environmental factors influence child development, behaviour and mental health – with a particular focus on epigenetics. Her expertise spans developmental psychopathology, childhood adversity, externalizing problems and epigenetic epidemiology. Her team’s research capitalizes on a range of interdisciplinary approaches, including genome-wide, system-level, and polygenic analyses as well as longitudinal structural equation modelling.

Frances Champagne
Department of Psychology, University of Texas at Austin
Adaptive Epigenetic Effects: Anticipating the Environment of Descendants

Epigenetic effects of the environment have been demonstrated across taxa and species and in response to a broad range of environmental conditions. These epigenetic effects are generally viewed as adaptations to the conditions of life that generate phenotypes that will promote survival and reproduction. This talk will highlight evidence that epigenetic effects occur both within and across generations leading to anticipatory phenotypes. The specific role of paternal and maternal influences on the transmission of these phenotypes will be explored. Future directions of this work will be discussed, including focus on the role of environmental stability and longevity in predicting epigenetic and phenotypic outcomes.

Frances A. Champagne is a Professor in the Department of Psychology at University of Texas, Austin and an Adjunct Associate Professor in the Department of Psychology at Columbia University. She received an M.Sc. in Psychiatry and Ph.D. in Neuroscience from McGill University. Dr. Champagne is a world leader within the evolving field of behavioral epigenetics—the study of how life experiences lead to behavioral and neurobiological variations. Though mechanistic studies in this field are addressed primarily in animal models, Dr. Champagne has also established collaborations to explore epigenetics within humans to determine the contribution of these molecular marks to neurobiological outcomes. In addition to her multidisciplinary research program funded by NIH, NIA, NICHD, NIEHS, EPA and NIMH, Dr. Champagne teaches several courses, including The Developing Brain, Ethics, Genetics and the Brain and Inheritance.

Troy Day
Queen’s University, Canada
The role of epigenetic inheritance in evolution

Professor Day will discuss how recent discoveries of non-genetic forms of inheritance fit within the broad structure of evolutionary theory. He will also evaluate claims that such discoveries call for a major revision of how we view the process of evolution.

Dr. Day holds degrees in Biology and Zoology, and a Ph.D. in Mathematics. He is a professor in the Department of Mathematics & Statistics and the Department of Biology at Queen’s University, working in the broad area of mathematical biology. His primary area of research is the study of evolutionary theory. Specifics topics of focus include the role of non-genetic inheritance in evolution, evolutionary epidemiology, eco-evolutionary modeling, life history evolution, and sexual selection. He is also interested in testing theory in collaboration with other researchers using a variety of experimental and correlative techniques.

Chathura J. Gunasekara
Baylor College of Medicine
Houston, Texas
Genomic Atlas of Systemic Interindividual Epigenetic Variation in Humans: A treasure map to guide the future of anticipatory medicine

A major obstacle to epigenetic epidemiology has been the cell type specificity of the epigenome. However, in specific genomic regions, DNA methylation remains consistent across the different types of tissues within an individual but varies between different individuals. In special genomic regions (9926 distinct sites which cover 0.1% of the human genome), the DNA methylation of any tissue of the human body can be assessed by measuring DNA methylation in easily obtainable tissue. Finding associations between DNA methylation in these regions with disease risk will unleash a new era for anticipatory medicine.

Dr. Gunasekara earned a Bachelor of Science degree in Computational Physics from the University of Colombo, Sri Lanka in 2010, followed by a Ph.D. in Computational Science and Engineering from Michigan Technological University, USA, in 2017, where he contributed to the field of Bioinformatics and Computational Biology through the development of machine learning algorithms and data analysis software platforms. His postdoctoral research in Baylor College of Medicine is focused on data-mining and knowledge discovery from DNA methylation data to predict disease risk using stable epigenetic biomarkers. His current work involves building predictive models using publicly available DNA methylation data to identify biomarkers which can be used to assess the one’s susceptibility to diseases in the future.

Bernhard Horsthemke, PhD
 University of Duisburg-Essen, Germany
 Genetic predisposition and phenotypic plasticity

The environment rarely has a direct effect on chromatin states, but affects cell growth and differentiation via signaling chains involving transcription factors; chromatin states just reflect these processes. In mammals and especially in humans, which have a strong Weismann barrier, there is no solid evidence for the inter- or transgenerational transmission of chromatin states and hence no evidence for epigenetic anticipation. What exists is a genotype dependent predisposition to phenotypic plasticity that allows the organism to adapt to changing environments in the future. Plasticity is anticipatory and of selective advantage, but a fixed chromatin state rarely is. Genetic determinism, which has rightly come under fire, should not be replaced with genetic denialism or epigenetic determinism.

Bernhard Horsthemke is a professor of human genetics at the University of Duisburg-Essen, Germany, and member of the National Academy of Sciences LEOPOLDINA. In 1982, he earned his Ph.D. in chemistry at the Technical University of Berlin and then moved into human genetics. After post-doctorial studies at St. Mary’s Hospital Medical School London, he set up his own lab at the Institute of Human Genetics in Essen. From 2001 to 2019 he was director of this institute. A major focus of his work has been the study of epigenetic mutations in human disease, especially imprinting disorders.

Simone Immler
Head, the Immler Lab
University of East Anglia, UK
The sperm factor: paternal impact beyond genes 

Dr Immler finished her PhD at the University of Sheffield, UK, in 2006. As a postdoctoral fellow, she moved to Uppsala University, Sweden in 2009 and in 2011, she founded her own lab in the same place. In 2017, she moved to the University of East Anglia, UK, where she is an Associate Professor. She is currently holding an ERC Starting Grant and is an Academy Fellow of the Knut and Alice Wallenberg Foundation, Sweden.

Jean-Pierre Issa, MD
Coriell Institute for Medical Research
Camden, New Jersey USA
Epigenetic reprogramming of aging and cancer phenotypes

The presentation will focus on efforts to identify druggable targets to reverse the epigenetic changes seen in aging and cancer tissues.

Dr. Issa earned his Bachelors of Science and Doctorate of Medicine degrees from The American University of Beirut, Lebanon, and completed his residency in internal medicine and fellowship in medical oncology at Good Samaritan Hospital and Johns Hopkins University, respectively, in Baltimore, Maryland. Dr. Issa’s current research focuses on mechanisms of epigenetic alterations in aging and cancer, translation of epigenomic studies for precision medicine, development of drugs for reprogramming the epigenome, and clinical trials of epigenetic therapy in cancer. He currently holds an academic appointment at the Fels Institute for Cancer Research, Temple University School of Medicine. His work has received a number of prestigious awards

Josep C. Jimenez Chillaron
Senior Investigator, Endocrine Division, Children’s Hospital Barcelona
Grandparental nutrition influences metabolic health in the following generations: From the past to the future through epigenetic landscapes

“We are what we eat.” However, recent research shows that parental and grandparental nutrition may influence health and disease risk of their near descendants. He will present an overview the molecular mechanisms by which ancestral diet conveys metabolic health in the future. Major emphasis will be held in the potential role of the epigenome. In sum, we are not only what we eat, but also what our parents and grandparents ate!

Dr. Jimenez earned a PhD in Biochemistry and Molecular Biology from the Universitat de Barcelona, Spain in 1999. Thereafter, he did post-doctoral training at Joslin Diabetes Center, Harvard Medical School in Boston, Massachusetts (2000-2005). He currently carries on research on Epigenetics and Disease Risk in the framework of Epigenesys at the Hospital Sant Joan de Déu, Fundació Sant Joan de Déu, Barcelona

Nancy Keller
Head, Keller Lab
College of Agricultural and Life Sciences
School of Medicine and Public Health
University of Wisconsin – Madison
Harnessing the fungal epigenome for drug discovery

A short history of epigenetics and fungal drug discovery will introduce the concept of how fungal natural products (source of potent pharmaceuticals and toxins) are produced by biosynthetic gene clusters (BGC) that lie in either heterochromatic or euchromatic regions of the fungal genome. Products produced by BGC in heterochromatin regions are cryptic or “silent,” but can be “turned on” by various actions, such as deleting or overexpressing histone modifying enzymes (e.g. HDACs). Examples from our laboratory research on such activation of novel drugs and the application of epigenetic machinery for mining the fungal genome will be presented.

Dr. Keller is Robert L. Metzenberg and Kenneth B. Raper Professor of Mycology, Department of Medical Microbiology and Immunology, Department of Bacteriology. She has over 30 years of experience in fungal genetics and development, host/microbe interactions, fungal/microbe/insect interactions and the genetics, biochemistry and activity of fungal secondary metabolite. The Keller Lab is considered a world leader in identifying virulence factors of pathogenic fungi. Research in which Dr. Keller was Principal Investigator has earned her funding from several prestigious organization and foundations.

Tae Hoon Kim
Head, Department of Biological sciences
University of Texas at Dallas
Richardson, Texas USA
Regulatory long noncoding RNAs

In addition to generation of transcripts that are ultimately processed and matured into mRNAs that are translated into proteins, a large number of long noncoding transcripts are generated in the nucleus. These long noncoding RNAs, including enhancer derived RNAs or eRNA, serve diverse regulatory roles and function through multiple mechanisms. How these RNAs may serve as persistent cellular memory to limit and shape regulatory potential of the genome will be discussed

Dr. Tae Hoon Kim earned his Ph.D. in Biochemistry from Harvard University and has held positions at several prestigious universities in the USA. He is an academic scientist whose independent and collaborative research efforts have yielded notable advances in the understanding of transcriptional regulation and genome expression in a number of health and disease relevant systems and models. He has developed and applied new approaches and techniques for uncovering novel control networks and mechanisms of gene expression, and has pioneered technologies for genome-wide mapping of active promoters, epigenetic marks and 5’ capped end of mRNAs. His laboratory has made critical contributions to the understanding of a key class of cis-regulatory elements known as insulators and their mechanisms of regulation.

Isabelle Mansuy
Group Leader and Co-Director
Brain Research Institute
University of Zurich, Switzerland
Epigenetic inheritance: Mechanisms involving the germline

Professor Dr. Mansuy will describe the concept of epigenetic inheritance in mammals and present current models. The presentation will focus on the model of early life adversity, how such a model can be analyzed in order to identify traits transmitted across generations, and the underlying molecular mechanisms in germ cells. It will also cover translational aspects of research in epigenetic inheritance.

Isabelle Mansuy is Professor in Neuroepigenetics at the Medical Faculty of the University Zürich (UZH), and the Department of Health Science and Technology of the Swiss Federal Institute of Technology Zürich (ETHZ). Her lab is part of the Center for Neuroscience-Zurich. She completed a PhD in Developmental Neurobiology at the Friedrich Miescher Institute in Basel, Switzerland and the Université Louis Pasteur Strasbourg, France. Dr. Mansuy`s research examines the epigenetic basis of complex brain functions and physiology in mammals and focuses in particular, on the mechanisms of epigenetic inheritance. The goal is to determine the molecular and cellular processes underlying the influence of life experiences on mental and physical health across generations. The research focuses on adverse experiences in early life and their link with psychiatric and metabolic disorders.

Ortrun Mittelsten Scheid
Senior Group Leader, Epigenetic Changes in Plants
Gregor Mendel Institute of Molecualr Plant Biology
Austrian Academy of Sciences, Vienna
Inheritance of directed epigenetic changes?

Stress, a state resulting from adverse circumstances, is a common experience of most organisms. It provokes specific, to a large extent reversible, physiological and metabolic changes. Stress can also modify epigenetic states, some of which can last beyond the stress exposure period. Whether the nature of such changes is also determined by the specific stress type, and whether the new states can be propagated to the progeny, is a matter of debate. Plants are great organisms for addressing these questions experimentally, as they can constantly form new organs, including germ cells, from somatic progenitors. This allows investigating the evidence for or against directed and durable epigenetic changes and its role in adaptation and evolution.

Dr. Mittelsten Scheid is a biologist specialized in molecular and genetic research in plants, focusing on epigenetic regulation of gene expression and DNA repair during stress and inheritance. After studying biology at the University of Hamburg, Germany, she worked as postdoctoral fellow at the Max-Planck-Institute for Cell Biology in Ladenburg, Germany, the Federal Institute of Technology (ETH) Zürich, Switzerland, and the Friedrich-Miescher-Institute for Biomedical Research in Basel, Switzerland. Since 2004, she has been the Senior Group Leader at the Gregor Mendel Institute (GMI) of Molecular Plant Biology. Besides training between 10-12 younger scientists in the lab, she is a member of several editorial and advisory boards.

Ruth Müller
Assistant Professor, Science and Technology Policy
Munich Center for Technology in Society (MCTS), Technical University
The Future is Now? Epigenetics and Intergenerational Responsibility

Epigenetics proposes novel pathways for how the social and material environment—toxins, nutrition, trauma or stress, etc.—can influence gene expression and health. Studies indicate that effects on life-course health can be particularly pronounced if exposures occur during early or prenatal life. Some researchers argue that effects might even be transmitted through the germ line. This “longue durée” (persistence) of epigenetic effects raises questions regarding intergenerational responsibility for the health (good and bad) of future generations, which will be explored in this presentation.
Originally trained in Molecular Biology, Ruth Müller holds a Ph.D. in Science & Technology Studies from the University of Vienna, Austria. She was a visiting researcher at the University of California-Santa Cruz, USA, and a postdoc researcher at Lund University, Sweden. Her work explores the nexus of science, technology, society, and policy, focusing particularly on how institutional norms and values shape and interact with knowledge production practices in academia, and on emergent knowledge cultures in the (post-genomic) life sciences.

Connie J. Mulligan
Head, Mulligan Lab
Department of Anthropology
University of Florida-Gainesville, USA
Epigenetics and psychosocial stress

Based on molecular genetic data to investigate questions about human health and disease, the presentation will focus with a specific focus on the investigation of epigenetic variation. Of special interest is the possibility that stress-derived epigenetic marks may be passed to future generations who did not directly experience the original stress.

Dr. Mulligan earned her Ph.D. in Molecular Biophysics and Biochemistry from Yale University. Broadly, she is interested in understanding the basis of patterns and levels of human genetic variation. Since 2010, she has studied the effect of violence and stress on mothers in the Democratic Republic of Congo and on their newborn’s health, with particular focus on a possible epigenetic mechanism to mediate this effect. In 2016, she began a collaboration to investigate risk and resilience in Syrian refugees living in Jordan. Her lab is investigating genetic and epigenetic variants that may influence response to trauma and mental health, and has just begun a new project to test for heritability of epigenetic marks of violence in three groups of three-generation families with contrasting exposures to the violence of war.

Cornelis Murre
Head, Murre Lab
Molecular Biology
University of California-San Diego, USA
The role of non-coding transcription in gene regulation.

Recently, the Lab found that non-coding transcription repositions enhancers from the lamina to the nuclear interior. The repositioning was orchestrated by large-scale changes in cohesin-dependent looping and CTCF occupancy. Specifically, these data showed how during developmental progression and tumor suppression non-coding transcription orchestrates chromatin folding and compartmentalization to direct with great precision enhancer-promoter communication. More recent findings describing the role of non-coding transcription in modulating gene expression and developmental progression will be presented.
Dr. Murre carried out his graduate work at Harvard Medical School and was a postdoctoral fellow at MIT. He is a Searle Scholar and the recipient of the National Institutes of Health Merit Award. He holds the positions of Distinguished Professor and Vice Chair of the Molecular Biology Section in the Division of Biological Sciences at UC-San Diego. His research efforts have been focused on elucidating the mechanisms and principles that underpin the folding patterns of the genome and how these relate to function. The goal of these studies is to visualize remote genomic interactions in live cells.

Mihai Nadin
Director, ante-Institute for Research in Anticipatory Systems
University of Texas at Dallas, USA
Anticipation, Evolution, Epigenetic

Anticipation, as the definitory characteristic of the living, is the foundation upon which evolutionary processes occur. Research has highlighted the role of epigenetic variation, in addition to genetic processes. On account of anticipation awareness, the unity between reactive processes (such as adapting to environmental changes) and proactive processes (that address the future as a possibility) is indicative of the complexity o evolutionary processes.

Dr. Nadin initiated the Study Group in Anticipatory Systems at the Hanse Wissenschaftskolleg in 2014. The Study Group organized three international conferences (2015, 2016) with the participation of over 100 scientists and educators from around the world. He is one of the founders of the field of studies called Anticipatory Systems, working in this domain since 1985. His currently focus is on foundational issues of anticipation and predictive computation, and in particular the significance of the anticipatory approach for medicine. At the invitation of the University of Texas, Dr. Nadin assumed the Ashbel Smith University Professor position, where he initiated Project Seneludens, applying interactive technology to maintain cognitive and physical health in the aging.

Mihai G. Netea
Head, Division of Experimental Medicine
Raboud Univeristy
Rotterdam, The Netherlands
Anticipating infection: trans-generational transmission of host defense against infections

Infections are one of the strongest environmental factors that exert evolutionary pressures on the host. Darwinian evolutionary processes relying on variation, selection and inheritance are the main mechanisms through which more effective immune responses against infections are selected during evolution. However, Darwinian evolutionary processes are slow and rely on chance variation, which can increase the risk for the population in case of major pandemic events with high mortality rates. Recent studies are emerging in the last decades that epigenetic changes, acquired during the life of an individual and protective against infections, can be transmitted trans-generational to protect the next generation of individuals. Such anticipatory Lamarckian evolutionary process can be complementary for the survival of a population during severe pandemic events.

Mihai Netea was born and studied medicine in Cluj-Napoca, Romania. He completed his PhD at the Radboud University Nijmegen, The Netherlands, on studies investigating the cytokine network in sepsis. After working as a post-doc at the University of Colorado, USA, he returned to Nijmegen where he finished his clinical training as a specialist in infectious diseases, and where he currently heads the division of Experimental Medicine, Department of Internal Medicine, Nijmegen University Nijmegen Medical Center. He is mainly interested in understanding the factors influencing variability of human immune responses, the biology of sepsis and immunoparalysis in bacterial and fungal infections, and the study of the memory traits of innate immunity. He is the recipient of the Spinoza Prize 2016 and an ERC Advanced grant in 2019, and member of the Netherlands Royal Academy of Science (KNAW).

Daniel Notterman
Head, Notterman Lab
Princeton University
Princeton, New Jersey, USA
Epigenetic signatures of social and environmental adversity: lessons from the Fragile Families Study

The Fragile Families and Child Wellbeing Study has closely followed a cohort of 5000 children and their mothers since 1998. Most of the families selected are poor and unstable, with high rates of single parenthood, and facing economic and social adversity. Every 3-5 years, social and demographic surveys have been conducted, together with health and environmental exposure. Since 2007, DNA methylation and genotype have been measured. To be presented and discussed are recent findings that connect epigenetic patterns and specific loci with social and environmental measures.

Dan Notterman is a pediatrician by clinical training and a biologist whose research examines interactions between genetic variants and environmental signals in the developing behavioral, cognitive and emotional phenotype of the child. He wishes to understand the interactions between specific genetic variants, environmental signals, and resulting behavioral and health outcomes. He holds the positions of Senior Molecular Biologist and Lecturer with Rank of Professor in Molecular Biology, at Princeton University.

Marcus Pembrey
Centre for Child and Adolescent Health
University of Bristol, UK
The Nature and Nurture of Inheritance and its Anticipatory Processes.

  The presentation will start with the 2006 Överkalix observation of male-line, sex-specific associations of ancestral food supply and longevity, plus its 2018 replication using the much larger Uppsala cohorts. It will be followed by a summary of the ALSPAC association studies of grandparental smoking with their grandchild’s developmental variation in growth, metabolism, myopia risk and IQ, plus emerging methylome correlates. The conclusion will present considerations of DNA damage / DNA repair response as a possible intergenerational signal.

Marcus Pembrey, a clinical geneticist, is FMedSci and Emeritus Professor of Paediatric Genetics at UCL Great Ormond Street Institute of Child Health, London. Initial research on the fragile X syndrome and the genomic imprinting disorder Angelman syndrome sparked his interest in epigenetics, and the possibility of transgenerational alterations in gene expression in response to environmental changes. The Överkalix work on transgenerational associations with ancestral food supply featured in a 2005 BBC “Horizon” program called “The Ghost in your Genes.” He collaborates in ongoing research in the framework of the Avon Longitudinal Studies of Parents and Children at the University of Bristol, using grandparental smoking in pregnancy as the exposure.

Nadine Provençal
Head, EpiGenOmics of Developmental Trajectories Lab
Simon Fraser University, British Columbia, Canada
Exposure to Early Life Stress and Glucocorticoids: Focus on Epigenetic Mechanisms.

Evidence indicates that exposure to early life stress can lead to long-term changes in several biological systems. One proposed mechanism is that excessive glucocorticoids (GCs) release after ELS exposure induces long-lasting epigenetic alterations in important regulatory genes. Dr. Provencal will present recent evidences from her research which support this hypothesis. Overall her work suggests that early GCs exposure primes future gene responses via epigenetic marks. Her findings using an in vitro model may translate to human pregnancy where epigenetic marks could potentially serve as a biomarker for prenatal stress exposure and contribute to the increased risk for developing a psychopathology observed with prenatal GC exposure.

Dr. Provençal completed her Ph.D. in epigenetics of early life adversity and aggression at McGill University, in collaboration with the Research Unit on Children’s Psychosocial Maladjustment in 2013. She received a research fellowship from the Canadian Institute of Health Research to complete a postdoctoral training at the Max-Planck Institute of Psychiatry (MPIP) in Germany. At the MPIP, she pursued her research on the epigenetic mechanisms involved in the response to stress in the context of psychiatric disorders. In 2014, she received the Richard Todd Award from the International Society of Psychiatric Genetics for her research contribution to the genetics of child psychiatry. Dr. Provencal joined the Faculty of Health Sciences at Simon Fraser University as Assistant Professor in March 2017 and heads the EpiGenOmics of Developmental Trajectories (EGODT) laboratory. She is also an Investigator at BC Children’s Hospital Research Institute.

Oded Rechavi
Head, The Rechavi Laboratory for Radical Science
George S. Wise Faculty of Life Sciences
Tel Aviv University, Israel
Inherited memories

Can we inherit memories? This controversial idea, which goes back to antiquity, was rejected since it violates a fundamental dogma known as “The Second Law of Biology.” Traits acquired during life should not become heritable. I will discuss our studies using C. elegans nematodes, which show that acquired traits can become inherited nevertheless. Not via DNA, but via inheritance of RNA molecules which obey different rules altogether. Most incredibly, we found that small RNAs made in the parents’ brain control the genes and behavior of the progeny, challenging basic concepts in genetics and evolution.

Professor Rechavi was selected as one of the “10 Most Creative People in Israel Under 40”, and one of the “40 Most Promising People in Israel Under 40.” In 2010, he obtained a Ph.D. in Biology from Tel-Aviv University (TAU). He conducted his post-doctoral studies in the Department of Biochemistry and Molecular Biophysics at the Columbia University Medical Center, New York. After establishing the Rechavi Lab at TAU in 2012, he showed that starvation produces a small RNA-mediated transgenerational effect that extends the progeny’s life span. Recently, the Rechavi Lab discovered rules and genes that determine which heritable epigenetic responses would be inherited to the progeny, and for how long each response would last. In a new study, the Rechavi Lab discovered that neurons can communicate with the germline control the fate of the progeny. Aside from his affiliations at Tel Aviv University, Oded Rechavi is a Senior Research Associate at the Van Leer Jerusalem Institute, and is a team member of the Allen Discovery Center, the Paul G. Allen Frontiers Group, Tufts University, Boston USA.

Xiaohua Shen
Principal Investigator, Xiaohua Shen Lab
Center for Life Sciences
Tsinghua University School of Medicine
Long non-coding RNA in stem cell and cancer biology

Much of the developmental complexity of higher eukaryotes is thought to arise from gene regulation rather than from an increase in the number of protein-coding genes. RNA represents a hidden layer of regulatory information in complex organisms. Long noncoding RNAs (lncRNAs) have been increasingly recognized as important regulators of transcription and chromatin structure. However, the functionality of vast majorities of lncRNAs is unknown. Identifying functional lncRNAs and revealing their regulatory mechanisms represent major challenges in understanding genome complexity and RNA-mediated gene regulation. I will discuss recent progress made in lncRNA and RBP-mediated regulation in contexts of transcription, chromatin, and stem cell pluripotency.

Xiaohua Shen received her Ph.D. at the University of Michigan and did the post-doctoral training at the Harvard Medical School. Xiaohua is a Cheung Kong Scholar and an Associate Professor in the School of Medicine at Tsinghua University. Xiaohua serves on the Editorial Board of Cell Reports. Her research interest is to understand how lncRNAs and genomic repeats influence chromatin structure, gene expression and cell fate in development.

Adelheid Soubry
Head, Epidemiology Research Group
Department of Public Health and Primary Care
KU Leuven, Belgium
Paternal influences on health of his progeny and the role of epigenetics

The concept of the Paternal Origins of Health and Disease (POHaD) paradigm will be presented, together with the Soubry Lab’s latest results regarding paternal effects on offspring health and epigenetic programming. Influences from pre-conception conditions, such as lifestyle, nutrition, obesity, pollutants, age, etc., are expected to induce epigenetically based defects in the next generations. Human studies on sperm and offspring samples are needed to understand the principles of epigenetic inheritance.

Adelheid Soubry, MSc, PhD, is an Epigenetic Epidemiologist and Director of the Epidemiology Research Centre at KU Leuven with an endless interest in the origin of life and etiology of diseases. She bridges multiple disciplines, holding several University degrees: Physics, (Bio)Medicine, and Molecular Biology, and Biotechnology. She received a Fulbright Award and did her postdoctoral training at the University of North Carolina-Chapel Hill, followed by a position at the Duke University Cancer Institute. She participated a 3-year interdisciplinary post-doc training program in Epidemiology, Public Health and Population Sciences at Duke University, funded by the NIH. She was honored a Toxicology and Environmental Health award by the Dr. M. Shannon Foundation. She has developed a new paradigm on paternal influences on offspring health (POHaD) and studies Epigenetics as an intermediate factor between paternal environmental exposures, early development and risk for non-communicable diseases in humans.

Prof. Dr. Daniela Cristina PLEA STEFAN
Global Clinical Leader, Oncology Diagnostics
F. Hoffman-La Roche, Ltd., Basel, Switzerland
Genes, us, and cancer
History of cancer and epigenetics (paradigm shifts in genetics), manipulation of epigenetic processes, cancer epigenetics: moving forward)

Dr Cristina Stefan is the oncology leader in APAC working for Roche for the past few years.

She is the first woman president of the African Organization for Research and Training in Cancer and also voted the most influential woman in business in Africa. After spending more than 25 years in Africa, founding a number of institutes such as African Cancer Institute and African Medical Research and Innovation Institute, pioneering the first South to South International twinning in cancer she continues to promote global oncology in Asia teaching at Duke Global Health Institute based in Singapore, as well at the Institute of Global Health in Geneva.

Moshe Szyf
Head, Szyf Lab
Department of Pharmacology and Therapeutics
McGill University, Montreal, Canada
Epigenetics behavior and experience.

The last century has seen an explosion of genetics research and genetic information culminating in the sequencing and decoding of the human genome. This has led to dominance of a deterministic view point that genetic differences between people explain the interindividual variation in behavior and temperament. Research in the last decade and a half has described biological processes that link experience and our genes. These processes involve “epigenetic” marking of genes. Epigenetic principles have an impact on our understanding of behavior that will be discussed.

Dr. Szyf is a geneticist and James McGill Professor of Pharmacology and Therapeutics at McGill University, where he also holds a GlaxoSmithKline-CIHR chair in pharmacology. He is also a Fellow of the Royal Society of Canada and the Canadian Academy of Health Sciences. Szyf’s main research interests lie with epigenetics, including behavioral epigenetics as well as cancer research. He pioneered research in DNA methylation for the last three decades and published more than 290 papers on the biological role of DNA methylation that span a broad spectrum from basic mechanisms to cancer diagnostics and therapeutics, as well as behavior, chronic pain, and addiction. Szyf pioneered epigenetic pharmacology in cancer and as well as the field of behavioral epigenetics. His studies provide a molecular link between environment and genes and between nurture and nature that had a wide impact on the social sciences and psychiatry. Last but not least, Szyf founded HKG epitherapeutics, which develops a novel class of epigenetic diagnostic markers for early detection of cancer and other diseases aimed for routine “check-up” in the general population to prevent disease and increase health and well-being.

Trygve Tollefsbol, Ph.D., D.O.
Professor of Biology
University of Alabama at Birmingham, USA
The epigenetic diet: Generational anticipation of nutrition-based cancer prevention through induced epigenetic modifications.

The reversibility of epigenetic changes that arise in early tumorigenesis allows novel approaches for cancer prevention. There is aberrant gene expression due to epigenetic changes in most cancers and bioactive dietary phytochemicals of the “epigenetics diet” can be used to neutralize epigenomic aberrations as they arise for cancer prevention. This epigenetic protective effect may be transmitted to the next generation allowing generational anticipation of cancer prevention.

Dr. Tollefsbol is a Professor of Biology and Senior Scientist at the University of Alabama at Birmingham. He has doctorate degrees in molecular biology and medicine, trained at Duke University and the University of North Carolina, and has published over 180 peer-reviewed papers and15 scholarly books, and has been featured as an Investigator in the Spotlight by the NIH and ScienceNow. He is an Associate Editor for Frontiers in Genetics, a contributing Editor of Lewin’s GENES classic textbook on molecular biology and is Lead Editor for Elsevier’s Translational Epigenetics Series. Dr. Tollefsbol’s research on epigenetics, cancer, and nutrition has been highlighted in eScience News and ScienceDaily. He has been investigating epigenetic mechanisms for over 25 years and is considered among the top three pioneering and leading researchers in the field of epigenetics,

Miklos Toth, M.D., Ph.D.
Head, Toth Lab
Professor of Pharmacology, Weill Cornell Medical College
New York, New York, USA
Epigenetic basis of anticipatory programming of behavioral adaptation across generations

Development creates thousands of bi-stable epigenetic switches in neurons that control, via gene and protein expression, neuronal phenotypes. Stochastic switching between epigenetic states produces cell-to-cell phenotypic variability. Cells with specific combinations of epigenetic switch-states respond to environmental inputs. Ancestral and early-life environment modulates stochasticity of epigenetic states to optimize behavioral responses to the expected environment.
Mismatch between early and later life environments leads to inappropriate behavioral responses

Dr. Miklos Toth is a neuroscientist, professor of Pharmacology at Weill Cornell Medical College in New York City, where he also has a medical practice. Born in Hungry, he earned his degree at the Semmelweiss University in Budapest. Recently, the Toth Laboratory became interested in environmental risk-factors in psychiatric disease (including early adverse care, sedentary lifestyle, chronic societal stress, psychological trauma, and drug use) because environment-induced disease conditions, similar to genetic conditions, can propagate across generations.

Kazuhiro Wada
Head, Molecular Neuroethology Laboratory Hokkaido University, Sapporo, Japan
Behavioral driven epigenetic regulation for vocal learning in songbirds

Vocal learning is the key behavioral basis for the acquisition of complex vocal patterns, like spoken human language. However, the learned vocal patterns do not suddenly emerge, but rather gradually develop through the long-term experience of vocal practice in the critical period. I will present the data showing that the self-motivated practice itself regulates the epigenetic dynamics for gene expression that are associated with vocal learning plasticity.

An Associate Professor in Faculty of Science, Hokkaido University, Japan, Dr. Wada obtained an M.D. in 1998 from School of Medicine, Kanazawa University. From 1998-2004, he studied biochemistry and neuronal signaling in songbirds and the effects of behavior on gene regulation, in order to determine the relationship of avian and mammalian brains using gene expression profiles. His post-doctoral research (at Duke University) examined the relationship between gene expression and learned vocal communication behavior. Currently, as Associate Professor at Hokkaido University, where he heads his own Laboratory, he studies the molecular and genetic mechanisms of vocal learning and species-specific learned vocalization.

Esther Walton
Senior Research Associate in Genetic Epidemiology
University of Bath, UK
Epigenetics of physical and mental ageing

The presentation will focus on research around healthy mental ageing. Using measures of accelerated epigenetic age and brain age, I will discuss how each ageing measure links to physical and mental health; the genetic architecture of both ageing measures; and modifiable lifestyle factors that impact accelerated ageing. Findings have important implications with respect to healthy mental ageing across populations.

Dr. Walton is an Assistant Processor in Clinical Psychology at the University of Bath. Her research centers on longitudinal epigenetic effects on mental health outcomes. She has expert knowledge on mental health research, including hyperactivity and behavioural difficulties, as well as mental health conditions such as anorexia nervosa and schizophrenia. She has a long track record of investigating brain imaging correlates of mental health conditions and how these link to genetic and epigenetic markers. In her research, she applies several approaches including methylome-wide association analyses, mixed and multi-level modelling, as well as causal inference methods such as Mendelian randomization. She also studies the life-course of these associations by applying longitudinal analyses on prospectively collected data from large UK and international cohorts.

Wei Xie
Head, XIE Lab
School of Life Sciences, Tsinghua University, Beijing, China
Epigenetic inheritance and reprogramming during mammalian early development

Drastic epigenetic reprogramming occurs during mammalian early embryogenesis. Deciphering the molecular events underlying these processes is crucial for understanding how epigenetic information is transmitted between generations and how life really begins. Probing these questions was previously hindered by the scarce experimental materials that are available in early development. By developing a set of ultra-sensitive chromatin analysis technologies, we investigated chromatin reprogramming during early mouse development for chromatin accessibility, histone modifications, and 3D architecture. These studies unveiled highly dynamic and non-canonical chromatin regulation during maternal-to-zygotic transition and zygotic genome activation. Recently, we further showed how the oocyte epigenome is established through extensive crosstalks of chromatin modifications, and how its defects exert a profound impact on embryonic development. Finally, I will also discuss how chromatin reprogramming occurs in other species including humans. Comparison among different species reveals both conservation and divergence during evolution in the molecular principles underlying epigenetic inheritance and reprogramming between generations.

Dr. Wei Xie is a Professor at the School of Life Sciences, Tsinghua University, and an HHMI International Research Scholar. After completing his graduate studies, he continued research in epigenetics and transcription regulation as a postdoctoral fellow at UCSD in 2009. He then joined Tsinghua University, School of Life Sciences as a Principle Investigator in 2013. Using interdisciplinary approaches, Dr. Wei Xie is dedicated to understanding how the epigenome is inherited, reprogrammed, and established in early development when life just begins. His work is among the first to demonstrate how chromatin accessibility, histone modifications, and higher-order chromatin structure are reprogrammed and regulated at the DNA level during early mammalian development.

Anthony S. Zannas, M.D., Ph.D.
Department of Genetics, School of Medicine
University of North Carolina, USA
Epigenetic Programming by Environmental Stress throughout Human Life

This talk will describe how psychosocial and other types of environmental stress can get biologically embedded through lasting epigenetic modifications. The possible mechanisms and cascade of molecular events responsible for this embedding will also be reviewed. The relevance of these epigenetic processes for shaping biological anticipation and anticipatory systems will be discussed.

Dr. Zannas is Assistant Professor of Psychiatry and Genetics at the University of North Carolina at Chapel Hill and Adjunct Assistant Professor of Psychiatry and Behavioral Sciences at Duke University, USA. Following completion of his medical degree and clinical work in Greece, Anthony obtained a master’s degree focusing on the Science of Stress at the University of Athens Medical School. He trained as a psychiatrist at Duke University and then completed a Ph.D. and post-doctoral degrees in Molecular Biology at the Max Planck Institute of Psychiatry and Ludwig Maximilian University in Munich, Germany. His research work examines how lasting epigenetic patterns result from stressful experiences, accrue throughout life, and can in turn shape health or disease trajectories.