Max Planck Society Yearbook

2020

  • What makes neurons unique: gene-regulatory mechanisms that dictate the identity and function of neurons

    2020 Hilgers, Valérie
    Neurons, also known as nerve cells, send and receive signals in our brain. They are particularly complex and fulfill functions that are unique to this cell type. Our research has shown that particular RNA sequences are of crucial importance for neurons to maintain their identity, and to develop and function properly. We study the gene-regulatory mechanisms that underlie the neuron-specific RNA landscape that drives neural function in health and disease.

2019

  • Hematopoietic stem cells - why vitamin A needs to protect them from activation

    2019 Schönberger, Katharina; Obier, Nadine; Pavlovich, Polina; Cabezas-Wallscheid, Nina
    Hematopoietic stem cells (HSCs) are essential for the lifelong production of blood cells. Our research demonstrated that specific molecular signals, like Vitamin A, keep HSCs in a sleep-like, dormant state protecting them from exhaustion and maintaining their long-term differentiation potential. As a reaction to stress, such as blood loss or infections, dormant HSCs are activated in order to regenerate the blood system in a quick manner. We are investigating the mechanisms responsible for the resting state to develop new therapeutic approaches for the treatment of blood-related diseases.

2018

  • Signalling fire of haematopoiesis

    2018 Lefkopoulos, Stylianos; Clapes, Thomas; Trompouki, Eirini
    Hematopoietic stem cells (HSCs) are a rare population capable of giving rise to all blood cells in our body. Understanding the molecular mechanisms of their development and maintenance can bring insights into how we could manipulate them ex vivo and treat hematological diseases. We use zebrafish and mouse as models to study HSC biology and focus on the role of inflammatory signaling in HSC generation during development but also HSC maintenance in adulthood. We are interested in transcription factors that cause HSC generation and are often deregulated in hematological diseases, like leukemia.

2017

  • Inheritance beyond DNA: intergenerational epigenetic inheritance

    2017 Zenk, Fides; Iovino, Nicola
    The genetic information for building an organism is transmitted from parents to offspring through gametes. Although it has long been thought that the DNA blueprint solely is encoded in our genes, increasing evidence shows that stress-induced changes in the chromatin can also be inherited through gametes affecting gene regulation across generations. Our recent research shows that an epigenetic modification, H3K27me3, is maternally inherited and controls gene expression during early embryogenesis. Future work will address the mechanisms underlying intergenerational epigenetic inheritance.

2016

  • Enlightening organelle function - live cell imaging reveals insight into metabolic communication strategies of immune cells

    2016 Rambold, Angelika
    In response to pathogens, immune cells activate a cellular program to eliminate harmful, infectious organisms and ensure our health. To mount a functional immune response, most immune cells require the reprogramming of their metabolic pathways. The scientists aim at gaining novel insight into how specific cellular compartments, so-called organelles, regulate such metabolic transitions. Of particular interest is hereby not only the function of individual organelles but also how inter-organellar communication drives metabolic immune cell programs and enables the fight against infections.
  • Pebbles in the mosaic: Which cells shape our organs and where do they come from?

    2016 Grün, Dominic
    Every organ in our body is composed of a multitude of single cells. Key to understanding the function of an organ is the knowledge of all the distinct cell types with their respective function plus their developmental pathways, with a so-called stem cell as a common starting point. Innovative novel molecular biology methods now permit the simultaneous quantification of thousands of molecules across single cells. This reveals a fingerprint of a cell, permitting to discriminate cell types of different function and to infer developmental pathways.

2015

  • The role of molecular chaperones during transcription: implications in biomedicine and evolution

    2015 Hummel, Barbara; Yoveva, Aneliya; Sawarkar, Ritwick
    Molecular chaperones are known for their role in folding of proteins in the cytosol. The research focus of the research group is to study these chaperones operating at chromatin, at sites of gene expression. In 2015, two important aspects of chaperoning at chromatin were discovered. Firstly, the mechanistic basis of buffering of genetic variation in gene promoters was elucidated. Secondly, an unbiased interaction network of Hsp90 at chromatin was uncovered in human cells paving a way for understanding anti-cancer properties of Hsp90 inhibitors.
  • In the spotlight: Cells of the innate immune response become illuminated in Freiburg

    2015 Lämmermann, Tim
    Upon entry of an infectious organism, cells of the innate immune response mediate a rapid immune reaction to eliminate harmful pathogens and protect our tissues. The researchers aim to gain novel insight into how different types of immune cells coordinate their behavior at inflamed tissue sites to mount an optimal immune response. By using a special form of microscopy, the researchers could already decipher the molecular mechanisms which allow phagocytes to form prominent cell swarms collectively fighting pathogens in infected tissues.

2014

  • Understanding why we’re fat, and why it matters

    2014 Lempradl, Adelheid; Pospisilik, Andrew
    Worldwide, over two billion individuals are overweight and associated diseases including type-2-diabetes, stroke and cancer provide a major healthcare challenge. Our laboratory aims to understand mechanisms underlying obesity. Here, two recent studies are summarized; the first highlighting the identification of the enzyme HO-1 as a probable input separating healthy from metabolically diseased obesity, and the second, mapping the pathways allowing a father’s diet to control future offspring obesity susceptibility.
  • Evolution of vertebrate immune systems

    2014 Swann, Jeremy; Boehm, Thomas

    All living beings possess immune systems to defend themselves against parasites and pathogens, which requires their ability to distinguish self from nonself. Scientists examine the evolution and function of vertebrate immune systems in order to determine design principles and any species-specific peculiarities. Furthermore, the scientists aim at reconstructing the immune functions of extinct species. With this knowledge, attempts are being made to generate artificial immune facilities for therapeutic purposes.

2013

  • A new model for transplantation of blood stem cells

    2013 Hess, Isabell; Schorpp, Michael
    Thymopoiesis is a very complex and dynamic process. The thymus is important for the differentiation and maturation of progenitor cells into self-tolerant T-lymphocytes. Failures in thymus development or thymus function cause immunodeficiencies; however, many genetic lesions underlying these diseases are still unknown. At the institute, researchers aim at a better understanding of the molecular and cellular mechanisms of thymus development.
  • Epigenetic identity and nuclear organization of centromeres

    2013 Padeken, Jan; Mendiburo, María José; Olszak, Agata; Schwarz, Hans-Jürgen; Heun, Patrick
    Centromeres are specialized genomic regions essential for proper chromosome segregation to the daughter cells. The researchers are interested in understanding how their identity and nuclear organization is regulated. Using the fruit fly Drosophila melanogaster it was recently shown that the centromere-specific histone CENP-A is a key epigenetic mark for centromere identity, both necessary and sufficient for centromere formation. We further identified Nucleoplasmin (NLP) to play a major role in the positioning of centromeres in the nucleus.

2012

  • Epigenetics: How male fruit flies compensate their missing X-chromosome

    2012 Akhtar, Asifa; Conrad, Thomas; Hallacli, Erinc

    The research focus of the Akhtar laboratory is to study epigenetic mechanisms underlying sex-specific X chromosomal gene regulation. The dosage compensation of the fruit fly (Drosophila melanogaster) constitutes a paradigm example of epigenetic regulation. In 2012, two important aspects of this mechanism were discovered: Firstly, important insights into the structure of the protein complex responsible for the dosage compensation were revealed and secondly the Akhtar lab could demonstrate the manner by which a protein complex in the nucleus influences the dosage compensation.

  • Heterochromatin – packaging artists at work

    2012

    Jenuwein, Thomas; Lachner, Monika; Roesch, Harald

    To fit the two-meter long DNA molecule into a cell nucleus that is only a few thousandths of a millimeter in size, long sections of the DNA must be strongly compacted. Epigenetic marks maintain these sections, known as heterochromatin. The research group, led by Thomas Jenuwein, at the Max Planck Institute of Immunobiology and Epigenetics investigates the molecular mechanisms necessary for the formation of heterochromatin. In particular, their research focuses on histone methylation.

2011

  • Immune tolerance induction in the gut

    2011 Izcue, Ana
    Functional immune systems rely on tolerance to self and harmless components of food and microflora. In mammals, immune tolerance is achieved through several mechanisms including a specialised T cell subset with a high constitutive expression of the transcription factor Foxp3. These so called regulatory T cells are especially important in the gut. The team of Ana Izcue analyses the factors required for the activity of regulatory T cells in vivo.
  • The role of autoreactivity in B cell development

    2011 Jumaa, Hassan
    Antibodies produced by B lymphocytes are able to recognize virtually any foreign antigen in the body. This enormous antibody diversity is generated by random somatic recombination of V-, (D-) and J-gene segments. In this process, autoantibodies can be generated that are directed against the body’s own structures and can thereby cause autoimmune diseases. However, scientists at the MPI for Immunobiology and Epigenetics could now show that the recognition of autoantigens is important for the selection and expansion of developing B cells.

2010

  • The Stability of Bob1 in B Cells

    2010 Nielsen, Peter
    Bob1 (also called OBF-1 or OCA-B) is a lymphoid transcription factor. While loss of Bob1 leads to impaired B-cell development and activation, over-expression of Bob1 could contribute to B-cell lymphomas. The amount of Bob1 protein in B-cells appears to be largely controlled by protein stability. Scientists at the Max Planck Institute for Immunology and Epigenetics are investigating how Bob1 stability is regulated during B-cell development.
  • RNA-binding proteins and microRNAs in the mammalian embryo

    2010 Winter, Jennifer
    Posttranscriptional regulation mediated by RNA-binding proteins and microRNAs is essential for proper development of the embryo. This is due to the fact that the embryo is a very dynamic system in which cells have to acquire new characteristics rapidly or have to migrate to distant places in the organism. Scientist at the Max Planck Institute of Immunobiology and Epigenetics study functions of RNA-binding proteins and microRNAs (miRNAs) in the developing mouse embryo.

2009

  • T-cell activation

    2009 Schamel, Wolfgang
    The immune system plays a central role for human health. Critically involved for its functioning is the activation of T-cells that relies on a complex intracellular signalling-network. To understand its behaviour, one has to study it in detail. Only then can one understand its dysfunction, as e.g. in case of tumors or infections, and develop novel drugs. Scientists at the MPI for Immune Biology have used biochemical and systemsbiology approaches to understand the function of the T-cell signalling-network. Of particular interest is the first element of the network, the T-cell antigen receptor (TCR-CD3) complex that recognizes foreign proteins.
  • Learning from Fish: Thymus Development in the Zebrafish

    2009 Schorpp, Michael
    The thymus is a primary lymphoid organ whose function is to provide mature and self-tolerant T lymphocytes required to fight infection and maintain tissue integrity. About 40 mutant zebrafish lines with aberrant thymus development have been established. The mutant genes so far identified show that the zebrafish model is an excellent tool to define novel genetic pathways important for T cell development. Live imaging analysis with these mutants and novel transgenic fish lines is used to examine the genetic basis of essential steps of thymopoiesis and to unravel their spatial and temporal characteristics.

2008

  • The important contribution of quantitative proteomics for deciphering the gene-regulatory code fo the human genome

    2008 Mittler, Gerhard
    The human genome contains roughly 25,000 protein-coding genes. However, in a given cell-type a maximum of only 10,000 of these genes are expressed at a significant level. In order to understand this, scientists have to know the gene regulatory code, which consists of the DNA sequence-dependent binding specificities of a prominent class of DNA-binding proteins, the so called transcription factors (TFs), which are able to read the regulatory information. Max-Planck researchers have devised a fast and sensitive technology bearing the potential for genome-wide studies of the gene regulatory code.
  • The role of cadherins during patterning of the mammalian embryo

    2008 Stemmler, Marc
    Cadherin-mediated cell-cell adhesion plays a pivotal role in patterning of multicellular organisms. In particular E- and N-cadherin have an important function during development and their expression is usually mutually exclusive. During important morphogenetic events expression is switched from E- to N-cadherin. This cadherin switch is observed during normal development, but also during tumorigenesis and metastasis and is accompanied by changes in cell morphology and their molecular properties. Scientists at the MPI of Immunobiology have focused on the molecular differences between and the gene regulation of E- and N-cadherin.

2007

  • Regulation and function of TGF-ß signals during early embryogenesi

    2007 Oelgeschläger, Michael
    Abstract Proteins of the transforming growth factor-beta (TGF-ß) family regulate a plethora of cellular processes. TGF-ß proteins regulate cellular differentiation as well as proliferation and mutations in the TGF-ß signal transduction pathway have been identified in various tumours. In addition, TGF-ß activity is of central importance for early embryonic development. Scientists at the Max-Planck-Institute of Immunobiology have identified new TGF-ß regulated genes that mediate TGF-ß activities during early embryonic development.

2006

  • Biological Patterning

    2006 Schlake, Thomas
    How does the complexity and variability of life develop from simple embryonic structures? Periodic body structures as well as characteristic colour patterns on the body surface clearly stress the existence of biological patterning processes. Although an astonishingly simple mathematical model could explain pattern formation, experimental proof was still missing. A combined experimental and computer modelling approach now provided evidence for the biological correctness of the hypothesised mechanism.
  • Mediators of Transcriptional Regulation

    2006 Borggrefe, Tilman
    All protein coding genes are transcribed by RNA polymerase II, the central enzyme in gene expression. A Mediator complex forms the bridge between transcriptional regulators and the RNA polymerase II machinery. Scientists at the MPI for Immunobiology recently gained first insights of the physiological function of the Mediator complex by using knock-out mice. They could show that Mediator is an essential coactivator for erythroid master regulator GATA-1. Therefore, mice lacking Mediator subunit Med1/TRAP220 are anemic and have a defect in the red blood cell development.

2005

  • Notch signaling and its key role in the neural stem cell differentiation

    2005 Taylor, Verdon
    Understanding the mechanisms that control the maintenance and differentiation of stem cells in the central nervous system of mammals is a key question in developmental and regenerative neurobiology. As the population ages, the occurrence of diseases that afflict the nervous system are becoming of prime importance and currently there are no therapies for the maintenance or replacement of neurons lost due to disease or damage in the brain. Scientists at the MPI for Immune Biology have focused on the identification of neural stem cells in the mammalian central nervous system, determining the niche and mechanisms that control neural stem cell development and addressing their potential for therapeutic cell replacement.

2004

  • The role of lipopolysaccharid in the interplay between bacteria and the immune system

    2004 Freudenberg, Marina A.
    The interaction of bacteria and other pathogenic microorganisms with the mammalian immune system has been the subject of world-wide investigations since more than a century now. The studies carried out in the group of Marina A. Freudenberg at the MPI for Immune Biology are concerned mainly with the interaction of lipopolysaccharide (endotoxin, LPS) with the innate immune system. LPS is a highly toxic component present in the outer cell-wall of Gram-negative bacteria, inducing in animals and humans a large spectrum of pathophysiological activities that can lead to shock and death. On the other hand LPS is a powerful activator of the innate immune system and plays a primary role in the early recognition of bacterial infections and in the stimulation of antibacterial defense. The positive and negative consequences of LPS/host interaction during bacterial infections, i.e. the induction of an early resistance to infection, the development of pathophysiological effects, as well as their underlying mechanisms are investigated by the group in different mouse-models. The objective of these studies is an improved diagnosis, prevention and treatment of infection and are therefore important both from the scientific and clinical point of view.
  • Quality control in the immune system

    2004 Boehm, Thomas
    How does the immune system avoid self-destruction and the devastating effects of autoimmunity that Paul Ehrlich described as “horror autotoxicus“? How did early vertebrates survive when they began to use receptors with random antigen specificities despite their extensive self-reactivity? It appears that the quality control mechanisms taming self-reactivity in the immune system were derived from an ancient mechanism that guided sexualselection on the basis of evaluating genetic diversity.

2003

  • The adapter protein SLP65 functions as tumour suppressor of childhood leukaemia

    2003 Reth, Michael; Jumaa, Hassan
    Signal transduction processes regulate the differentiation of B cells. Deregulation may result in immunodeficiency, autoimmunity or lymphoproliferative diseases. Mice lacking the adaptor protein SLP-65 show a block in B cell differentiation and an increased incidence of pre-B cell leukaemia. Moreover, the tumour suppressor function of SLP-65 seems to be required for the inhibition of pre-B cell leukaemia in humans.
  • Embryonic patterning via gradients of BMP signaling

    2003 Oelgeschläger, Michael
    The Bone morphogenetic proteins (BMP) belong to the TGF-ß family of secreted growth factors and regulate fundamental events in early development of vertebrate as well as invertebrate embryos. In particular, the formation of a functional BMP signalling gradient, established by the localised secretion of BMP antagonists, is essential for the determination of cell fate along the future dorsoventral or back-to-belly body axis. Michale Oelgeschläger and his team have identified a number of new genes that are regulated by the BMP signalling gradient in Xenopus laevis. One of these genes is involved in the regulation of cellular movements rather than cell fate determination and might help to unravel the relationship of cellular movements and cell fate determination during early embryonic development.
  • Zebrafish as a model for immunological research

    2003 Schorpp, Michael
    The group of Michael Schorpp at the MPI in Freiburg is interested in identifying genes that are important for thymopoiesis in the zebrafish. They study mutant fish lines that were generated by chemical mutagenesis and display aberrant thymus development. Affected genes are isolated by positional cloning and their biological function elucidated in fish and mice using a variety of methods. These studies are of medical relevance as they might lead to more refined diagnosis and novel therapeutic modalities for inborn or acquired immune deficiency syndromes.
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