Participating Groups

Beckers Group, Gene Regulation and Epigenetics (IEG)

Research Focus:

The Group of Gene Regulation & Epigenetics is interested in understanding the mechanisms of epigenetic inheritance of the predisposition to develop obesity and diabetes over generations. Having discovered that parental malnutrition predisposes the offspring to develop a more severe metabolic syndrome, which is transmitted via mammalian oocytes and sperms, we are now focusing on the epigenomic signatures in gametes. Parental malnutrition changes epigenomic signatures in gametes at multiple levels. We use an embryogenic approach to understand which of the dramatic epigenomics changes in the gametes are responsible for the enhanced phenotype in the offspring. In addition, we have initiated several projects to study the reversibility of the epigenetic inheritance of the metabolic syndrome. These include the experimental assessment of nutritional supplements that effect epigenomic signatures as well as mutli-generational approaches.

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Bonev Lab, 3D Genome and Molecular Neurobiology (Pioneer Campus)

Research Focus:

The Bonev Lab studies how epigenetic identity is related to cell fate and what are the functional implication of chromatin remodeling to the temporal and spatial heterogeneity in the brain. To accomplish this, they focus on the interplay between transcription factors, 3D nuclear organization and gene expression in vivo and using cerebral organoids. Their research is highly interdisciplinary and combines developmental neurobiology, single cell –omics, mouse genetics, genome engineering and computational biology. The long-term objective of the Bonev lab is to decipher the genetic and epigenetic blueprints of cortical development and evolution.

Colomé-Tatché Group, Computational Epigenomics (ICB)

 

The Colomé-Tatché group works in the Institute of Computational Biology. Her group aims to develop new computational methods for the integration and interpretation of datasets generated from single cell / low input technologies as well as "classical" bulk experiments, such as (single cell) DNA methylation and (low input) histone modifications.  In addition, her group also works on modelling epigenetic processes, such as the inheritance of epigenetic states and the stochastic gains and losses of epigenetic marks. The overall aim of their research is to develop robust computational methods that allow for a better understanding of processes involving epigenome dynamics, and how epigenomic changes affect the phenotype.

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Drukker Group, Human Pluripotent Stem Cells (ISF)

Research Focus:

The research aim of the Drukker lab is to investigate the mechanisms governing the potency and differentiation of pluripotent stem cells (PSCs). Epigenetic regulation plays a critical role in these processes, and therefore mutations in epigenetic factors or environmental stress can lead to disease. To understand normal and pathologic development, we focus on investigating transcription, histone modifications, and posttranscriptional regulation and the relationship to the dissolution of pluripotency and the commitment of developmental progenitors that give rise to our organs. We also model epigenetic disorders using patient and genetically engineered iPSC models that we differentiate in vitro to disease relevant cell types and organoids.

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Durner Group, Epigenetics and Acclimation (BIOP)

Research Focus:

Subject of our research is the interaction of epigenetic and metabolic dynamics in response to environmental change. We particularly focus on the connections between histone/DNA methylation and one-carbon metabolism, which produces the universal methyl donor S-adenosylmethionine. Using highly interdisciplinary approaches, including genetic and chemical screening, high-throughput phenotyping, genomics, and metabolomics, we aim to reveal new regulatory mechanisms, which will help to understand the causes and consequences of epigenetic variation in plant populations.
With Arabidopsis as model organism, we take advantage of the vast genetic resources that are available, including gene silencing reporter lines that we have generated. In contrast to mammals, Arabidopsis tolerates losses of DNA methylation, which greatly facilitates genetic analyses. Moreover, changes in DNA methylation often lead to epialleles that are heritable over many plant generations. This allows us to associate epigenetic variation with different traits and explore the potential of epigenetics in the development of stress-resistant crops.

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Eick Group, Molecular Epigenetics (MEG)

Research Focus:

Mammalian RNA polymerase II (Pol II) has evolved a carboxy-terminal domain (CTD) consisting of 52 hepta-repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Post-translational modification of CTD is a prerequisite for transcription of chromatin templates and proper 5’-capping, splicing, and 3’-processing of mRNA. Histone modifications serve as manual for the recruitment of CTD modifying enzymes to transcriptionally engaged Pol II. Inversely, CTD modifications are critical for the recruitment of histone modifying enzymes. The current model implies that the cross talk between CTD and chromatin plays a central role for reading and writing of epigenetic information. In our project we study the different post-translational modifications in CTD and their functions in gene regulation.

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Gieger Group, Molecular Epidemiology (AME)

Götz Group, Neural Stem Cells (ISF)

 

Magdalena Götz and her team aim to elucidate the key mechanisms of neurogenesis in the developing and adult brain and then use them for repair purpose. The aim of their research is to identify mechanisms important for neurogenesis and to find ways of reactivating them following brain injury. To do this they study neurogenesis during development, at postnatal stages and in particular areas of the adult forebrain where neurogenesis occurs, using zebrafish, mice and human in vivo and in vitro approaches. The identified molecular mechanisms are then used to turn various cell types into neurons by direct reprogramming and study the molecular mechanisms of this conversion process.

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Hammerschmidt Group, EBV Genetics and Vectors (AGV)

 

Research Focus:

Epigenetic regulation of EBV’s life cycle.

The situation:

When EBV infects a human cell, the viral DNA is epigenetically naïve, i.e. it lacks nucleosomes, is free of histone proteins and does not contain 5’-methylcytosine residues. The outcome of EBV infecting any cell is nonproductive and a latent infection ensues. Later, upon chromatinization of the viral genomic DNA and incorporation of 5’-methylcytosines the latently infected cells can support EBV’s lytic phase.

The questions:

How does the epigenetically naïve EBV DNA acquire its characteristic epigenetic signature? What are the factors involved in chromatinization? Is chromatinization essential to establish a latent infection?
The perspective:

Knowing the crucial steps in chromatinization is a prerequisite to consider means and measures that can prevent viral infection and abrogate the co-existence of the virus and its host cell.

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Hamperl Group, Chromatin Dynamics and Genome Stability (IES)

The genetic information stored in DNA must be accurately expressed, duplicated and maintained to allow cellular proliferation, differentiation and development to a multicellular organism. Eukaryotic DNA replication starts at multiple sites throughout the genome and is necessarily coordinated with other chromosomal processes including transcription, chromatin assembly and maturation, recombination and DNA repair. Notably, chromosomes provide the fundamental scaffold for all these dynamic and in part simultaneously occurring processes. Using cell biological, genetic and proteomic approaches in yeast and human cells as model organisms, the Hamperl group is interested in characterising and identifying the molecular players that allow DNA replication and transcription to occur simultaneously on our chromosomes - without major accidents leading to DNA damage and genome instability, a hallmark of cancer and many other human diseases.

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Heinig Group, Genetic and Epigenetic Gene Regulation (ICB)

Research Focus:

The Heinig team aims to develop and apply computational and statistical tools for the identification of molecular regulatory networks underlying common diseases and the genetic and epigenetic mechanisms controlling these networks from population level DNA and multi-omics data sets. A special focus is the molecular characterization of metabolic and cardiovascular diseases, in particular diabetes and arrhythmias like atrial or ventricular fibrillation.  In doing so, they aim to provide a deeper mechanistic or systems level understanding of disease processes.

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Hrabě de Angelis Group, Functional Genetics (IEG)

Jeremias Group, Apoptosis in Hematopoietic Stem Cells (AHS)

Research Focus:

The aim of the Jeremias lab is to uncover basic biologic mechanisms that represent suitable targets for anti-cancer therapy. In acute leukemias as model disease, the majority of tumors reveal early, if not initiating mutations in epigenetic regulators so that leukemias might be considered as epigenetic diseases. Our lab tries to understand how altered epigenetic regulation is required for tumor cell growth and survival and how epigenetic alterations can be addressed therapeutically. As example, we study chromosomal translocations involving the epigenetic regulator KMT2A (MLL) with the final aim to find new treatment options for the challenging subgroup of KMT2A -rearranged leukemias.

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Kempkes Group, Viral Latency (AGV)

Epstein-Barr virus infected B cells can express at least four distinct cellular transcription programs by switching between defined sets of viral gene expression patterns. Like all herpes viruses, EBV switches between virus producing lytic and latent infection. Each of these well-defined epigenetic states mirrors physiological B cell differentiation stages which are tightly controlled by the virus. While latently infected cells phenocopy blast-like, germinal center or resting memory B cells, virus producing B cells phenocopy antibody producing plasma cells. The Kempkes group studies the molecular processes that initiate and balance the switches between the different epigenetic stages in B cells. Currently we study the impact of B cell pioneer factor EBF1 and long non-coding RNAs on the control of co-regulated gene clusters residing in chromatin domains.

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Lindermayr Group, Redox-dependent chromatin modulation (BIOP)

Research Focus:

In mammalians, redox-stress alters global histone modification and nitric oxide and reactive oxygen species have been described as new architects of the epigenetic landscape. The focus of our research covers basic mechanisms that are conserved or analogous between plants and animals. We want to analyse the role of redox signaling in epigenetic regulation and its implications in plant fitness and development. We aim to understand how plant redox systems are altered in response to changing redox-active atmosphere (enhanced NOx, CO2, O3, temperature) and how plant epigenomes respond to such different climate scenarios over multiple generations. This will allow us to generate a map of global scenario-specific responses of the histone acetylome/methylome (Epi-Proteomics). Systematic depletion of known deacetylases we help us to establish enzyme-substrate relationships and unveil a crosstalk between neighboring modifications. Moreover, we want to reveal how this responses affect plant performance and if the redox system is a key player at the interface between environment and plant epigenomes and phenotypes.

Marr Group, Quantitative Single Cell Dynamics (ICB)

Research Focus:

Combinations of histone modifications regulate gene expression and can be measured with mass spectrometry based proteomics. However, it is often difficult to assess what mechanisms generate the observed abundances of these combinations. Together with their experimental partners, the Marr group develops mathematical models that describe the dynamics of histone modifications during cell cycle or developmental processes. They use mass action dynamics and model selection to infer parameters and find reaction networks that best describe the measured data.

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Ninkovic Group, Neurogenesis and Regeneration (ISF)

Research Focus:

Jovica Ninkovic and his team perform basic and translational research in the field of the central nervous system (CNS) repair and regeneration.  Their aim is to indentify novel strategies for brain repair and regeneration by modulating the function of glial cells. Using the mouse and zebrafish as model systems, the Ninkovic team combine in vivo imaging with cell type-specific omics approaches to understand multi-gene interactions in vivo and in real-time in the regenerating adult zebrafish brain and implement them in the mammalian brain for the regeneration purposes.

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Rosemann Group, Radiation Biology (ISB)

Research Focus:
  
The Rosemann team focus their research on three main areas: Chromatin architecture and radiation epigenetics, DNA repair in mesenchymal stem cells, and Genetic instability and cellular aging.  They aim to understand the effects of low dose radiation exposure on the development of cancer and degenerative diseases.  In addition, they study the effects of aging and low dose chronic irradiation on genomic stability and mesenchymal stem cell potency, an important stem cell population in adult mammals.

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Scheel Group, Mammary Stem Cells (ISF)

Research Focus:

Plasticity, defined as the ability of cells to dynamically change cell state, generates cellular heterogeneity and drives regenerative processes and tumor progression in epithelial tissues. This emerging realization challenges fundamental concepts of tissue formation and complicates developing precision medicine approaches for regeneration and oncology. As a research group, we focus on defining mechanisms of plasticity during human mammary gland morphogenesis, maturation and breast cancer progression. We use organoid assays, functional genomics and single-cell analysis and work on constantly developing and improving new tools for culturing primary human cells.

Schmoller Group, Cell and Organelle Size Control (IFE)

Research Focus:

Total protein content typically increases in direct proportion to cell volume. However, because DNA content remains constant, certain DNA binding proteins need to be differentially regulated to ensure the correct DNA-to-protein stoichiometry. The Schmoller group uses a combination of single-cell microscopy and biochemical bulk assays to identify the molecular mechanisms responsible for the distinct cell-size-dependence of histone homoestasis in the model organism budding yeast.

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Schneider Group, Chromatin Dynamics and Epigenetics (IFE)

 

Research Focus:

The Schneider team aims to decipher the molecular mechanisms underlying epigenetic inheritance and function, with the long-term goal of understanding and tackling epigenetic distortions in disease, stem cell maintenance and metabolism.  In their studies of chromatin modifications, the team endeavors to identify novel sites and types of novel histone modifications, explore links between environment, metabolism and chromatin structure and to establish the mechanisms through which chromatin modifications are integrated within the cell in healthy and diseased states. Their research also investigates epigenetic inheritance in yeast and mammalian cells, as well as the expression and function of histone H1 variants in development and disease.

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Scialdone Group, Physics and Data-based Modelling of Cellular Decision Making (IES)

Research Focus:

The Scialdone lab investigates the role of epigenetic mechanisms during cellular decision making, with a focus on embryonic development. In particular, they analyse the interplay between the epigenome and the chromatin spatial organization, which dynamically change during fate decision.

To this end, the Scialdone group integrates the analysis of 'omics data and the development of physical models, to get insight into the underlying molecular mechanisms.

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Stricker Group, Epigenetics Engineering (ISF)

Research Focus:

The aim of the Stricker lab is to investigate which of the myriad of epigenetic marks have significant functional relevance in mediating stem cell or disease phenotypes.  Through the development of molecular tools enabling the manipulation of epigenetic marks, the Stricker team aims to identify epigenetic inducers of cell fates and associated changes in desease.

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Teperino Group, Environmental Epigenetics (IEG)

Research Focus:

The Teperino group  is interested in identifying the epigenetic contribution to metabolic disorders within and across generations. On this regard, they have recently identified an unexpected role for the histone variant macroH2A1.1 in mitochondrial respiration (Posavec, Teperino*, Buschbeck* – NSMB*corresponding authors). they are currently dissecting the role of the Polycomb Repressive Complex 2 (PRC2) in metabolic control. In particular, the group has identified Indian Hedgehog as a novel hepatokine, which is controlled by PRC2 in the liver and regulates whole body energy homeostasis (Teperino R. et al. Cell 2012; and in preparation).

As a natural follow up to these studies, we are exploring the role of Polycomb across generations in several models of epigenetic inheritance of diabetes and obesity in mice (such as paternal overweight and circadian disruption); and we are trying to identify new mediators of non-genetic inheritance (such as cytokines and hormones).

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Theis Group, Machine Learning (ICB)

The Theis group works on a variety of topics related to Machine Learning in the context of computational biology. They apply existing state-of-the-art Machine Learning algorithms and develop novel methods tailored towards solving complex biological and medical questions. Their current research focus lies in the analysis of heterogeneities in single cell profiles e.g. from single cell transcriptomics.

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Torres-Padilla Group, Epigenetics and cell-fate in early mammalian development (IES)

Research Focus:

The Torres-Padilla group is interested in understanding the molecular mechanisms behind epigenetic reprogramming, the acquisition and loss of totipotency and the underlying cell fate decisions, during the earliest stages of mammalian development, after fertilisation of the oocyte by the sperm. Combining state of the art live imaging approaches, super-resolution microscopy, cell biology and embryological approaches in vivo with large scale omics analyses the team aims to better understand chromatin structure and function in embryonic development and how nuclear organisation impacts gene expression and the acquisition of different cell fates. 

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Uhlenhaut Group, Molecular Endocrinology (IDO)

 Research Focus:

The Uhlenhaut lab investigates mechanisms of transcriptional regulation by nuclear hormone receptors using mouse genetic and genomic approaches. These receptors recruit different coregulator complexes and histone modifiers in response to ligand. They are currently studying different histone modifications mediating hormone action in both innate immune cells and metabolic organs, with relevance to human disease.

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Winkelmann Group, Neurogenomics (ING)

 

Research Focus:

The Institute of Neurogenomics works on both monogenic diseases and multifactorial disorders. The potential epigenetic mechanisms in these conditions are of major interest. In case of childhood-onset dystonia, for instance, we recently found the causative gene by identifying mutations in KMT2B which encodes a lysine-specific histone methyltransferase (Zech et al 2016). For the multifactorial restless legs syndrome a large-scale epigenome-wide association study (EWAS) is under way, searching for variation in DNA methylation that is associated with the disorder.

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Yildirim Group, Experimental Pneumology (CPC/iLBD)

Research Focus:
 
Chronic obstructive pulmonary disease (COPD) is a life-threatening lung disease, currently the third leading cause of death worldwide, characterized by chronic bronchitis, small airway remodeling and emphysema. It is a major global health problem, associated with high health-care costs and currently no curative therapy.
Although cigarette smoke remains the greatest risk factor for COPD, epigenetic modification has recently emerged to be another key player in the pathogenesis of COPD. A lesser known epigenetic regulating event is the post-translational modification of proteins by the addition of methyl groups to arginine residues by a family of intracellular enzymes termed protein arginine methyltransferases (PRMTs). Protein arginine methylation is a unique class of protein modification involved in cellular processes such as cell proliferation, differentiation, apoptosis and senescence.  The Yildirim team works to decipher the role of protein arginine methyltransferases (PRMTs) in the pathogenesis COPD. To that end they recently demonstrated that deficiency of Coactivator-associated arginine methyltransferase 1 (CARM1) or PRMT4 attenuated SIRT1-regulated anti-senescence, and thus induced senescence in alveolar epithelial cells resulting in an increased susceptibility to emphysema in mouse lung. As PRMT activity appears to be dysregulated in numerous human diseases, including heart disease and cancer, these enzymes may be potential novel therapeutic targets against COPD.

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Zeggini Group, Institute of Translational Genomics (ITG)

The Institute of Translational Genomics leverages big data in genetics and genomics for medically important human traits. We aim to translate insights from genomics into mechanisms of disease development and progression, shortening the path to translation and empowering precision medicine.

We use integrated multi-omics and systems genomics to enhance our understanding of the genetic and genomic aetiology of disease development and progression. Specifically, we integrate proteomics, gene expression, methylation and genomic information obtained from disease-relevant primary tissues collected from patients, or studied in cellular and organismal models of disease. Our aim is to move from discovery to functional interpretation and ultimately to clinical application. Our approach is underpinned by data generation at scale and by the development of computational genomics toolkits to analyse the wealth of information.

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