Contributions to the Yearbook of the Max Planck Society
2023
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Sleeping embryos as a survival strategy
2023 Bulut-Karslioglu, AydanDiapause enables numerous animals to delay pregnancy until environmental conditions become more favorable by pausing the development of their embryos. Whether human cells can also undergo diapause is a subject of debate. We are utilizing in vitro models to explore the mechanisms through which mouse embryos regulate diapause. Our research holds promise for biotechnological applications and could contribute to a deeper understanding of the phenomenon of quiescent cells in various biological contexts.
2022
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How protein droplets cause hereditary disease
2022 Hnisz, Denes; Ballaschk, MartinThe cell, like many of its components, consists of small vesicles with a fatty envelope. Molecules can move around freely inside these envelopes. But there are other complex structures that are not strictly bounded from their environment. They can change dynamically and are made of a large number of different molecules. These molecular condensates play an important role in gene regulation and disease.
2021
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X-Chromosome as a model for genetic regulation
2021 Schulz, Edda G.The inactivation of one of the two X chromosomes in females can not only explain various inheritable diseases, but also allows us to study how the activity of our genome is controlled. X inactivation is governed by the Xist gene, which is able to silence an entire chromosome. Although this process appears to be restricted to mammals, the underlying regulatory mechanisms are used in various contexts of genome regulation.
2020
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Trunk development in a dish
2020 Herrmann, Bernhard G.; Veenvliet, Jesse V.The ontogeny of a complex organism from a single cell demands a high level of self-organization of stem cells and their descendants. The current 2-D model of cell differentiation in culture does not support the formation of embryo-like structures. By using a new 3-D culture system we were able to show that embryonic stem cells of the mouse are indeed able to form trunk-like structures comprising primordia of the spinal cord, cartilage, bone, and skeletal muscle in a culture dish. Our method strengthens a new field of research: Synthetic Embryology.
2019
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In the thicket of biological regulation
2019 Vingron, Martin; van Bömmel, Alena; Heinrich, Verena; Ramisch, Anna; Ballaschk, MartinWe are pursuing fundamental questions of biology: How do cells work, what are the processes within and how do these processes affect each other? After all, interaction of billions of molecules is what constitutes life. Hence, we try to understand the complexity of biological systems through mathematical models and the analysis of large-scale data. Particularly the dynamic regulation of genes is a continuous source for new and surprising discoveries.
2018
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Writing DNA methylation in mammalian genomes
2018 Galonska, Christina; Charlton, Jocelyn; Mattei, Alexandra; Meissner, AlexanderDuring the development of an organism, the sequence of its DNA remains unchanged. Gene activity, however, is epigenetically controlled by reversible modifications of the DNA sequence, such as methylation of cytosines. We are working on the development of a system for targeted methylation of the genome at defined positions. Thus, we hope to gain a comprehensive understanding of the role of DNA methylation for the regulation of gene activity, thereby paving the way for the development of new therapeutic approaches for a range of diseases.
2017
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Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors
2017 Risch, Thomas; Abdavi-Azar, Nilofar; Jandrasits, Christine; Amstislavskiy, Vyacheslav; Worth, Catherine L.; Warnatz, Hans-Jörg; Sultan, Marc; Herwig, Ralf; Lehrach, Hans; Yaspo, Marie-Laure; in Kooperation mit dem OncoTrack Konsortium (www.oncotrack.eu)Colorectal carcinomas (CRC) are clinically challenging tumors. To identify novel predictive biomarkers of the therapeutic response, the OncoTrack consortium recruited 106 CRC patients for establishing a biobank of organoids and xenografts models analysed by sequencing and tested in a pre-clinical platform. This unique resource generated a compendium of data for advancing our understanding of CRC. Linking molecular patterns with drug response profiles identified novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.
2016
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From possibilities and necessities in epigenetics
2016 Kinkley, Sarah; Helmuth, Johannes; Chung, Ho-RyunChromatin modifications provide information above the DNA sequence. The modifications correlate with transcriptional activity, constitute a memory of past decisions, and are thought to provide a state that enables future decisions. The direct measurement of a at the end conflicting combination of chromatin modifications revealed that this combination is not a reflection of molecular potential, as has been thought, but is required to dampen the mutation rate within important genes. Hence, chromatin modifications are key players keeping the DNA sequence in shape and thereby influence evolution.
2015
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Our genome in 3D - how DNA-folding regulates our genes
2015 Mundlos, StefanThe folding of chromatin is an inherent property of the genome to incorporate the DNA in the cell nucleus. Recent advances using chromosome conformation capture technologies have shown that the genome is folded in structured domains, so-called TADs. Structural variations, as they often occur in human genetic disease, can interfere with TAD configuration and thus result in altered gene expression and consecutive disease. By re-engineering human aberrations in mice it was shown that TADs and their boundaries are an essential component when interpreting structural variations.
2014
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Molecular networks in genome and proteome analysis
2014 Stelzl, UlrichMolecular networks are data-based descriptions of molecular interactions in a cell. Today, a wealth of physiologically relevant protein information is available, obtained from cells under different conditions, from different systems or disease states, including information on genetic variation, protein levels, and post-translational modification. Molecular networks are useful frameworks to distinguish causal from other molecular alterations that are only consequence or do not substantially contribute to the phenotype. This way, molecular networks are also increasingly important for medicine.
2013
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Long non-coding RNAs as regulators of transcription in human
2013 Ørom, UlfThe "Long non-coding RNAs" (ncRNAs) research group is focusing on the molecular mechanisms of long non-coding RNAs. In particular, the scientists are studying how these transcripts are involved in transcriptional regulation and long-range gene activating functions. The goal is a better understanding of fundamental processes underlying regulation of gene expression. The detailed understanding of the complex class of ncRNAs is limited, however, their importance for gene regulation and disease progression is obvious, following studies in both basic science as well as clinical research. -
Are there two classes of promoters?
2013 Vingron, MartinA mathematical analysis of human gene promoter sequences shows that these promoters fall into two distinct classes. A number of features correlate with these two classes, suggesting that this distinction is actually a reflection of different regulatory mechanisms. This article summarizes sequence features and biological properties specific for the promoters of the two classes. We explain how a mathematical analysis of whole-genome data could point towards particular biological mechanisms.
2012
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A truly selfish gene and its supporters
2012 Herrmann, Bernhard G.At fertilisation, we get one set of chromosomes from each parent and, in general, pass on either the paternal or the maternal allele of each gene with equal frequency to our children. This has been taught by Mendel. According to Richard Dawkins’ hypothesis, however, there are selfish genes which are not content with random selection and thus actively promote their increased transmission to the next generation. Evidence for this assumption comes from a mouse gene that is transmitted at a frequency of up to 99% from males to their offspring. -
Novel systems biology research for a personalized medicine in cancer
2012 Nietfeld, Wilfried; Lehrach, HansThe solution of many medically important aspects depends on the prediction of the behaviour of complex networks, e.g. biological networks active within a tumor but also in other tissues of a patient under complex conditions, for example a particular therapy. So far, it is not possible to predict the success of a specific therapy for a specific patient. We are sequencing the genome of individual cancer patients as well as the genome and transcriptome of their tumor as a basis of a virtual-patient-model, used to predict effect and side effects of specific therapies on the individual patient.
2011
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Nutrigenomics: natural modulation of gene expression
2011 Sauer, SaschaThe scientific focus of the research group lies on the systematic analysis of the modulation of gene and protein expression. This process can be specifically influenced by the interaction of genes and natural products, which are e.g. derived from food. We analyse if and by which mechanisms natural products interfere with genes or gene products. The interdisciplinary approach comprises basic and applied research. The results can be useful for optimised application of natural products to improve various metabolic processes. -
Better late than never: Genome research turns to rare diseases
2011 Ropers, Hans-HilgerFor more than 15 years, genome research has looked for clinically relevant genetic risk factors for common diseases, with meagre results. Now rare disorders come into focus of genome research worldwide. Scientists at the Department of Human Molecular Genetics have successfully dealt with rare genetic disorders for many years. Since the introduction of novel, affordable sequencing techniques it has become possible, in principle, to elucidate the molecular causes of all single gene disorders, with far-reaching consequences for diagnosis, prevention and therapy.
2010
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Neurodegenerative disorders – from yeast to neurodegenerative processes
2010 Krobitsch, SylviaLate onset neurodegenerative disorders are progressive disorders, which usually strike during mid-age of affected individuals and with age result in profound neuronal degeneration. Even though these diseases are quite common worldwide, the mechanisms responsible for their pathogenesis are, in most cases, poorly understood, and effective preventative therapies for these devastating disorders are currently not at hand.
2009
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Give me five! Or six? Or seven?
2009 Kuss, PiaGive me five, high five, hello and good bye - all shown to others with one hand. Certainly everyone knows that this hand comprises five digits. But not everyone is born with exactly five digits. In humans, occasionally hereditary skeletal limb malformations do occur. One malformation, the so-called synpolydactyly, implies that patients are born with additional digits, and those are fused above all. This phenotype develops due to a mutation within the Hoxd13 gene, leading to a lack of retinoic acid and thereby causing uncontrolled cartilage production at wrong sites in the extremity. -
Protein networks: How protein interactions define shape and function of cells
2009 Stelzl, UlrichSystematic protein interaction studies are an important part of functional genomics research. A powerful method to decipher protein-protein interaction networks is the yeast two-hybrid system that allows studying the possible interaction of billions of protein pairs. Resulting interactions are represented in protein networks which provide a framework for a systems understanding of the molecular biology of the cell and contribute to medical practice, facilitating identification of human disease genes and an improved interpretation of patient samples and records.
2008
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Computational modelling of biological processes
2008 Wierling, Christoph; Herwig, RalfThe development of computational models for biological processes opens the possibility to predict new effects of virtual targeted perturbations that can in turn be validated by experimental observations. Such predictions are highly relevant for many practical applications, for example the development of new drugs. Through the last years, the Bioinformatics group has been developing different tools, methods, and databases that support the computational modeling of biological processes, such as the pathway integration database ConsensusPathDB and the modeling system PyBioS. -
The interconnection of mutagenic and cellular processes during the evolution of mammals
2008 Arndt, Peter F.The huge amount of DNA sequence data derived from a multitude of species, which is at our disposal today, allows comparative studies of genome evolution. Such studies afford to trace back the evolution of genomic DNA sequences and to single out and study the processes that play an important role in changing and shaping the genomes of mammals. The interaction of these processes with other cellular operations is now being investigated and better understood.
2007
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Interaction networks in protein structures
2007 Lappe, MichaelThe central topic of the Bioinformatics / Structural Proteomics group is the analysis and prediction of protein structures via networks. Methods are developed to reconstruct the 3D structure from such networks with the aim to identify the determining contacts in these structure networks. This interdisciplinary work provides potential application in protein and drug design. -
Regulatory networks of trunk formation in mammals
2007 Herrmann, Bernhard G.Mesoderm formation is an important process of embryonic development. It plays an essential role in trunk formation and organ development in mammals. It is controlled by several interacting signalling pathways, which also play an important role in tumour progression. Novel methods are utilized for deciphering the complex regulatory networks comprising thousands of gene products, which control mesoderm formation in the embryo and in tumours.
2006
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Mathematical models demonstrate the integration of information through cellular signal transduction pathways
2006 Klipp, EddaMolecular approaches reveal components and mechanisms of cellular stress sensing and adaptation. In addition, mathematical modeling has proven to foster the understanding of some basic principles of signal transduction and signal processing as well as of sensitivity and robustness of information perception and cellular response. Main modeling principles are exemplified here for a model organism, the yeast Saccharomyces cerevisiae. -
Newly recognized functions of monoaminergic hormones: protein monoaminylation
2006 Walther, Diego J.After the finalization of the human genome project, investigations into the transcriptome, proteome, and metabolome have been largely increased, since their concurrence determines the functionality of genes. In this context, recent mechanistic discoveries have induced a kind of “paradigm shift” regarding the mode of action of hormones and widened our understanding of these compounds in cell and gene regulation, particularly when involved in human diseases.
2005
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Molecular mechanisms of skeletal development
2005 Mundlos, StefanThe research group Development & Disease focuses on the molecular basis by which form and structure of the skeleton are regulated during vertebrate development. Our approach combines research on human genetic disorders with gene function analysis in vitro and in animal models. The studies are carried out in close collaboration with the Institute of Medical Genetics at the Charité, Berlin. Recent advances in the identification and functional analysis of human gene mutations have provided new insights into the biology and pathology of limb malformations and, in particular, in the mechanisms of joint formation. Genetic screens have identified a large number of novel genes that are currently investigated for their role in normal bone development, in disease, and during the regeneration of bone and cartilage. -
Ribosomes, the cellular production plants of proteins, loose their secrets
2005 Fucini, Paola; Nierhaus, Knud H.Ribosomes translate the genetic DNA information into the amino-acid sequence of proteins and are one of the most complicated structures of the cell. High resolution methods such as X-ray analysis and cryo-electron microscopy as well as improved functional methods have led to a quantum leap in our understanding of the mechanisms of the ribosome by deducing functionality from structure.
2004
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Analysis of binding sites for the activation of genes
2004 Vingron, MartinTranscription factors play a central role for the regulation of genes. The Department of Computational Biology at the MPI for Molecular Genetics utilizes a panel of mathematical methods to analyze function and interaction of transcription factors in order to achieve new insights into gene regulation. -
From genetic information to the treatment of diseases
2004 Lehrach, HansThanks to the sequencing of the human genome, we have access to detailed and extensive information about the complexity of biological processes. The comparison of the human genome with the chimpanzee genome leeds to a better understanding of molecular processes. This will set up a basis for the advancement of new medical diagnostics and treatments.
2003
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Molecular basis of hereditary cognitive disorders
2003 Ropers, Hans-HilgerMental retardation is the biggest unsolved problem of Medical Genetics and a major burden for Health Care. Most severe forms of mental retardation are due to chromosome aberrations and gene defects, but so far, only a small proportion of these defects is known. For the mapping and identification of the relevant genetic factors we employ four different complementary strategies: i. investigation of patients with balanced chromosome rearrangements; ii. development and application of methods for high-resolution detection of unbalanced changes in the DNA; iii. systematic search for mutations in families with X-linked mental retardation; and iv. mapping of autosomal recessive gene defects by identifying homozygous genome segments in children of consanguineous parents. During recent years we have already identified numerous molecular causes of cognitive disorders. The characterization of these genes promises major progress for the diagnosis and prevention of mental retardation as well as new insights into normal and disturbed brain development and function. -
Regulatory networks during embryogenesis of vertebrates
2003 Herrmann, Bernhard G.The development of the body anlage with its organs is controlled by a multitude of complex regulatory mechanisms which follow a strict order. On top of these processes is the formation of mesenchyme, an event with similarities to metastasis formation of tumors. Novel methods are utilized to unravel regulatory networks controlling mesenchyme formation and tissue differentiation.