Seminar Colour Guide:              
External Faculty Speaker
Friday, 20 January 2017, 11:00Add to calendarDissecting the hypothalamic circuits that regulate appetiteDeniz Atasoy , Istanbul Medical University, TurkeyHost: Cornelius GrossCNR Seminar Room, EMBL Monterotondo
Abstract: Novel tools for mapping and manipulating molecularly defined neural circuits have improved the understanding of how the central nervous system regulates appetite. Activation of starvation-sensitive AGRP neurons can rapidly elicit behavioral state similar to food deprivation, which present an entry point for reverse-engineering neural circuits for hunger. We mapped functional synaptic interactions of AGRP neurons with multiple cell populations in mice and probed the contribution of downstream elements to feeding behaviour using optogenetic and pharmacogenetic techniques. We have also developed tools for detailed structural analysis of AGRP neuronal connections using serial-section electron microscopy. Our results characterized some basic features of functional and anatomical circuit organization for appetite regulating pathways.

Seminar given by an external postdoc
Monday, 23 January 2017, 10:00Add to calendarFibrosis and transdifferentiation of cardiomyocytes during zebrafish heart regenerationHector Sanchez Iranzo, Spanish National Centre for Cardiovascular Research, SpainHost: Alba Diz-MunozSmall Operon, EMBL Heidelberg
Tags: Cell Biology
External Faculty Speaker
Tuesday, 31 January 2017, 13:15Add to calendarRegulation of endocytosis by the stress-activated protein kinase Hog1 in S. cerevisiaeGerhard Seisenbacher, Universitat Pompeu Fabra, PRRB, Barcelona, SpainHost: Cristina Vieitez and Nassos TypasSmall Operon, EMBL Heidelberg
Company Representative
Thursday, 2 February 2017, 09:30Add to calendarRoles and selection procedures in IndustryPeggy Klein, Thermo Fisher Scientific, GermanyHost: Monika Lachner & Rachel Coulthard-GrafSmall Operon, EMBL Heidelberg
External Faculty Speaker
Friday, 3 February 2017, 13:00Add to calendarNovel approaches for computer aided drug discoveryVladimir Poroikov, Institute of Biomedical Chemistry, Moscow, Russia, Russian FederationHost: Victor LamzinSeminar Room 48e, EMBL Hamburg
Abstract: Among the numerous ligand-based drug discovery tools PASS occupies a special place because its development has been started over 20 years ago. During the past years PASS is improved and extended permanently. Current PASS version predicts 7,157 biological activities with average accuracy 94.6% based on structure-activity relationships elucidated from the training set consisted of 959,801 biologically active compounds. To analyze PASS predictions, we developed another computer program PharmaExpert, which provides analysis of the mechanism-effect relationships between the biological activities, analysis of possible positive and negative pharmacokinetic and pharmacodynamic drug-drug interactions, etc. Using PASS and PharmaExpert, novel pharmaceutical agents have been discovered with anxiolytic, anti-inflammatory, antihypertensive and other actions. We identified a nootropic action in known antihypertensive drugs Perindopril, Quinapril, and Monopril that is likely not related to their antihypertensive effect; therefore, PASS may be used for drug repurposing. To find new anticancer agents by virtual screening, we have analyzed dozens of millions of structures from ChemNavigator database and selected a few dozen compounds for biological testing. Two out of eleven tested compounds were found to be potent anticancer NCEs, with synergistic action to the known p53 reactivator RITA. In addition to PASS, which predicts activity at the qualitative level (active/inactive), we developed computer program GUSAR. GUSAR can be used for the creation of (Q)SAR models for the prediction of properties of organic compounds belonging to both homogeneous and heterogeneous chemical classes. GUSAR superiority was shown in comparative studies with many other popular ligand-based drug design methods. Application of PASS, GUSAR, and PharmaExpert not only significantly increases the chances for the discovery of novel more safety and potent pharmaceutical agents, but also provides an estimation of biological activity profiles for drug-like substances in chemical biology.
Since the reasonable quality of our computational tools PASS and GUSAR has been already demonstrated in many internal and independent studies, we decided to create Way2Drug platform (www.way2drug.com), which provides several tools for bioactivity prediction jointly with the interface for input of novel information by the user. This additional information may be used to improve the quality of the (Q)SAR models by re-training the predictive programs. Currently, a few predictive programs are presented at Way2Drug portal: PASSOnline predicts over 4000 kinds of biological activity; GUSAROnline predicts acute rat toxicity and interaction with antitargets; CLC-Pred predicts cytotoxicity for tumor and non-tumor cell-lines; DIGEP-Pred predicts drug-induced changes of gene expression profiles; SOMP predicts sites of metabolism by five major drug-metabolizing isoforms of P450; MetaTox generates structures of metabolites and predicts the integral toxicity of parent compound and its metabolites; etc.
Currently, in the framework of joint Russian-Indian project we are developing the next generation of Way2Drug platform, targeted to drug repurposing. This integrated tool will combine the ligand-based, target-based and network pharmacology approaches, to optimize the discovery of safer and more potent pharmaceutical agents.
External Faculty Speaker
Thursday, 9 February 2017, 14:00Add to calendarShared mechanisms and interactions of the immune and nervous systemManuel Friese, Universitätsklinikum Hamburg-Eppendorf Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Zentrum für Molekulare Neurobiologie Hamburg (ZMNH) , Hamburg, GermanyHost: Paul HeppenstallCNR Seminar Room, EMBL Monterotondo
Abstract: When individual cells of the immune or nervous system exchange information and process incoming signals, they rely on a limited set of receptors, signalling molecules and transcription factors that are central for information processing. The pathways involved have been repurposed multiple times during evolution, leading to genetic pleiotropies and shared signalling networks. Moreover, the immune and the nervous system also directly interact at several sites in the body, ensuring homeostasis, but chronic inflammation can result in neurodegeneration. We identified interacting pathways that intrinsically modulate resilience of neurons toward inflammatory stressors. In addition, by analysing signature gene transcripts of immune cells and cells of the nervous system we identified close relationship of transcript expression in distinct nervous system cells and specialized immune cells. In particular migratory dendritic cells (migDC) of the skin express genes, which were previously thought to be exclusive to neurons. Migratory dendritic cells are highly specialized antigen-presenting cells of myeloid origin that continuously transport antigen from peripheral tissues, such as the skin to secondary lymphoid organs, where they induce and regulate immune responses. We described a neuronal plasticity molecule that is functionally required for inflammatory locomotion in migrating DC, while its expression is exclusively restricted to migDC. We demonstrated that neuronal plasticity molecules allow functional identification of migrating DC, while the protein itself is driving DC migration by regulating actin dynamics. These are examples of co-evolution and direct interaction of the immune and nervous system, which can be therapeutically explored.
EMBL - Sapienza Lecture
Friday, 10 February 2017, 11:00Add to calendarReverse Replay during Human Problem SolvingPeter Dayan, Gatsby Computational Neuroscience Unit, Sainsbury Wellcome Centre, 25 Howland Street, London W1T 4JG, United KingdomHost: Cornelius Gross / Andrea MeleSapienza Università di Roma - Aula Odeion - Museo dell'Arte Classica - P.le Aldo Moro, 5 - Roma
Abstract: The fast replay of sequences of neural representations has been suggested as supporting learning and online planning. However, it has largely been studied in spatial tasks in rodents. I will show how we came upon reverse replay during our latest attempt to use the decoding of MEG data to capture the process of human model-based planning in a non-spatial sequential decision-making problem. During epochs in which our subjects were planning, their brains spontaneously visited representations of approximately four states in the problem in fast sequences lasting on the order of 120 milliseconds. These sequences followed backward trajectories along the permissible paths in the task.
I will discuss the possible implications of this finding.

This is joint work with Zeb Kurth-Nelson, Marcos Economides and Ray Dolan.

Tags: Neurobiology
Science and Society
Tuesday, 14 February 2017, 15:00Add to calendarWhy time does not heal all wounds: Chronic PainRohini Kuner, Medical Faculty, Heidelberg University, GermanyHost: Halldór StefánssonLarge Operon, EMBL Heidelberg
External Faculty Speaker
Thursday, 16 February 2017, 11:00Add to calendarGenerators of diversity and the host-pathogen interfaceNina Papavasiliou, German Cancer Research Center (DKFZ), GermanyHost: Judith ZauggSmall Operon, EMBL Heidelberg
Abstract: Unlike most static cells in the body, immune cells constantly migrate through environments that vary considerably both in steady state and during invasion by a pathogen. The unpredictability of these environments can be thought of as a selective force that through evolution has favored substantial population diversity in cells of the immune system. Diversification can happen at the level of DNA (through recombination or mutation) to produce, for example, novel receptors on B cells (antibodies), than can better deal with pathogens. Not surprisingly, similar types of processes also occur in pathogens, for the purposes of evading a targeted antibody response. The African trypanosome is the best example of the counter response to antibodies by a pathogen. The interaction of B cells and trypanosomes is direct, and occurs at the molecular interface that is represented by the surface coat of each (antibody and VSG coat respectively). Each of these molecular surfaces is rapidly evolving in its own right but together they are nevertheless locked in an arms race, and form a system that is the best representative of the Red Queen hypothesis , an evolutionary paradigm that is of substantial theoretical but also practical (therapeutic) interest.Tags: Cell Regulation and Signaling, Evolution, Molecular Medicine
EMBL Distinguished Visitor Lecture
Tuesday, 21 February 2017, 11:00Add to calendarFrom Systems to Structure: Bridging Networks and MechanismNevan Krogan, University of California, USAHost: Balca Mardin/Benjamin LangThe Operon, EMBL Heidelberg
Abstract: There is a wide gap between the generation of large-scale biological data sets and more-detailed, structural and mechanistic studies. However, recent work that explicitly combine data from systems and structural biological approaches is having a profound effect on our ability to predict how mutations and small molecules affect atomic-level mechanisms, disrupt systems-level networks and ultimately lead to changes in organismal fitness. Our group aims to create a stronger bridge between these areas primarily using three types of data: genetic interactions, protein-protein interactions and post-translational modifications. Protein structural information helps to prioritize and functionally understand these large-scale datasets; conversely global, unbiasedly collected datasets helps inform the more mechanistic studies. Our efforts in this respect are presently focused on model organisms, including yeast and bacteria, as well as in mammalian cells, with a particular focus on pathogenesis.
External Faculty Speaker
Thursday, 23 February 2017, 11:00Add to calendarTo be announcedDavid Barford, MRC-LMB (Cambridge, United KingdomHost: Irina CornaciuEMBL Seminar Room, EMBL Grenoble
Science and Society
Thursday, 23 February 2017, 18:00Add to calendarWie Gliazellen zu Nervenzellen werden neue Ansätze zur Therapie nach GehirnverletzungenMagdalena Götz, Ludwig-Maximilians-Universität München, GermanyHost: Halldór StefánssonPrint Media Academy
Abstract: Das menschliche Gehirn kann abgestorbene Nervenzellen größtenteils nicht mehr ersetzen. Um dies zu ändern, untersuchen wir die Mechanismen, wie Nervenzellen während der Entwicklung gebildet werden, um dies dann auch im erwachsenen Gehirn nach Verletzung auslösen zu können. Tatsächlich werden Nervenzellen während der Entwicklung von radialen Gliazellen gebildet, einem Zelltyp der bislang nur als Stützzelle angesehen wurde. Diese Gliazellen gehen bei der Reifung des Säugergehirns verloren und differenzieren in andere Gliazellen aus. Dementsprechend geht auch die Fähigkeit zur Bildung neuer Nervenzellen in den meisten Gehirnregionen verloren, mit Ausnahme weniger Regionen, in welchen radiale Gliazellen erhalten bleiben, und tatsächlich zeitlebens noch neue Nervenzellen gebildet werden. In vielen anderen Wirbeltieren bleiben diese Gliazellen weitverbreitet erhalten (Barbosa et al., Science 2015), und Gehirnverletzungen können ohne Narbenbildung völlig geheilt werden (Baumgart et al., Glia 2010). Wir arbeiten daran zu verstehen, wie diese radialen Gliazellen Nervenzellen bilden, und wie wir die Bildung von Nervenzellen auch in den differenzierten Gliazellen des Säugergehirns wieder auslösen können (als Übersichtsartikel: Masserdotti et al., Development 2016). Diesbezüglich haben wir gerade in den letzten Jahren große Fortschritte gemacht und es gelingt uns nun, viele narbenbildende Gliazellen in reife Nervenzellen nach Gehirnverletzung im Mausmodell umzuwandeln (Gascon et al., Cell Stem Cell 2016). Zudem konnten wir zeigen, dass auch Gehirnregionen, in denen normalerweise keine neue Nervenzellen im Erwachsenenstadium gebildet werden, die Fähigkeit besitzen, neue Nervenzellen wieder passend in das Nervenzellnetzwerk zu integrieren und die Funktion der abgestorbenen Nervenzellen wieder zu ersetzen. Die große Frage ist nun, ob dies auch für lokal aus Gliazellen umgewandelte Nervenzellen möglich ist.
External Faculty Speaker
Friday, 24 February 2017, 10:00Add to calendarTo be announcedTam Mignot, CNRS, Aix-Marseille University, FranceHost: Nassos TypasSmall Operon, EMBL Heidelberg
External Faculty Speaker
Friday, 24 February 2017, 11:00Add to calendarLong lasting trans-generational epigenetic transmission of environmental informationBen Lehner , Centre for Genomic Regulation (CRG), Barcelona, Spain, SpainHost: Jamie HackettCNR Seminar Room, EMBL Monterotondo
Abstract: Since Darwin and Lamarck, biologists have speculated about the possibility of the inheritance of acquired traits. In our work on the causes of inter-individual variation we chanced upon an example of a >10 generation epigenetic memory of environmental change in C. elegans. We have been using this as a model system to understand how information about the environment can be transmitted for many generations without establishing permanent epigenetic states. I will present this work and also our work on the epigenetic consequences of impaired DNA replication.
External Faculty Speaker
Thursday, 2 March 2017, 11:00Add to calendarOpportunities and Challenges Using the Other Omics for Precision MedicineErnest Fraenkel, MIT Department of Biological Engineering, USAHost: Judith ZauggSmall Operon, EMBL Heidelberg
Abstract: Rapid advances in high-throughput technologies, including next-generation sequencing, proteomics, and metabolomics, are providing exceptionally detailed descriptions of the molecular changes that occur in diseases. However, it is difficult to use these data to reveal new therapeutic insights. Despite their power, each method only captures a small fraction of the cellular response. Moreover, when different assays are applied to the same problem, they provide apparently conflicting answers. Furthermore, data from clinical samples sometimes make each patient appear unique. I will show how network modeling approaches integrate disparate data to reveal functionally coherent pathways. These networks can identify features common to subgroups of patients that may provide critical insights for targeted therapies.Tags: Biocomputing, Biological Networks, Cell Regulation and Signaling, Gene Regulation, Systems Biology
EMBL - Sapienza Lecture
Friday, 3 March 2017, 11:00Add to calendarEpigenetics and Rett SyndromeAdrian Bird, Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland, United KingdomHost: Cornelius Gross / Irene BozzoniSapienza Università di Roma - Aula Odeion - Museo dell'Arte Classica - P.le Aldo Moro, 5 - Roma, EMBL Monterotondo
EMBL Distinguished Visitor Lecture
Friday, 10 March 2017, 10:00Add to calendarTo be announcedEve Marder, Brandeis University, Faculty of Biology, Waltham, MA, USA, USAHost: Philip Avner / Cornelius GrossCNR Seminar Room, EMBL Monterotondo
EMBL Distinguished Visitor Lecture
Tuesday, 21 March 2017, 11:00Add to calendarTo be announcedJürgen Knoblich, Institute of Molecular Biotechnology, AustriaHost: Anne Ephrussi, Jan EllenbergThe Operon, EMBL Heidelberg
External Faculty Speaker
Thursday, 23 March 2017, 11:00Add to calendarTo be announcedGraziano Martello , Universita delgi Studi di Padova, Dipartimento di Medicina Molecolare, Padova, Italy, ItalyHost: Jamie HackettCNR Seminar Room, EMBL Monterotondo
Abstract:
External Faculty Speaker
Thursday, 30 March 2017, 11:00Add to calendarTo be announcedKay Diederich, University of Konstanz, GermanyHost: Irina CornaciuEMBL Seminar Room, EMBL Grenoble
EMBL - Sapienza Lecture
Friday, 31 March 2017, 11:00Add to calendarTransgenerational epigenetic inheritance: Evidence in mammals and potential mechanisms involving the germlineIsabelle Mansuy, University of Zürich and ETH Zürich, Zurich, SwitzerlandHost: Cornelius Gross / Andrea MeleSapienza Università di Roma - Aula Odeion - Museo dell'Arte Classica - P.le Aldo Moro, 5 - Roma, EMBL Monterotondo
Science and Society
Friday, 31 March 2017, 15:00Add to calendarThe problem with pseudoscienceMichael D. Gordin, Princeton University, USAHost: Halldór StefánssonLarge Operon, EMBL Heidelberg
Science and Society
Friday, 7 April 2017, 11:00Add to calendarTracking large-scale outbreaks using infectious disease genomicsKristian Andersen, Scripps, STSI Department of Immunology and Microbial Science, La Jolla, California, USAHost: Halldór Stefánsson CNR Seminar Room, EMBL Monterotondo
Abstract: Tracking large-scale outbreaks using infectious disease genomics
Hamburg Speaker
Friday, 7 April 2017, 13:00Add to calendarTo be announcedMatthias Wilmanns, EMBL Hamburg, GermanySeminar Room 48e, EMBL Hamburg
Science and Society
Friday, 7 April 2017, 14:00Add to calendarTransparent Publishing, Preprints & Open Science: how to share reproducible dataBernd Pulverer, EMBO, GermanyHost: Erika Pellegrini ILL Chadwick, EMBL Grenoble
Abstract: The biosciences are witnessing a rapid growth and diversification of research. Scientific progress depends on efficient mechanisms to select, quality control, archive, share and find reliable and reproducible research. The research paper remains the predominant mode of sharing peer-reviewed research findings, and a subset of scientific journals play important roles also as a proxy for quality and impact in research assessment. I will discuss how the editorial and peer review process at highly selective journals can be reformed to assess both the interest and quality of the claims made by a researcher, and also the reliability, reproducibility and integrity of the experimental data.
I will discuss forward looking policies and publishing modalities that facilitate sharing and discoverability of research data with minimal delay, focussing on EMBO Source Data policies and technology and Preprint servers. I will discuss the promises and challenges of the nascent preprint movement in the biosciences and highlight how preprints and papers can form a continuum for fast and reliable research communication.
In times of limited funding, the pressures to publish in a subset of journals can increase dramatically. I will discuss the challenges this poses to the publication process in the context of reproducibility and scientific integrity. I will discuss how a metrics centric research assessment process can undermine the quality of the research process, highlighting the San Francisco Declaration for Research Assessment (DORA) and other initiatives.
External Faculty Speaker
Thursday, 20 April 2017, 11:00Add to calendarTo be announcedFrancesca Mattiroli, Luger Lab, JSCBB, University of Colorado Boulder, 3, USAHost: Valentina SperanziniEMBL Seminar Room, EMBL Grenoble
Hamburg Speaker
Friday, 21 April 2017, 13:00Add to calendarTo be announcedAnne-sophie Huart, EMBL Hamburg, GermanySeminar Room 48e, EMBL Hamburg
EMBL Distinguished Visitor Lecture
Monday, 24 April 2017, 11:00Add to calendarNutritional Regulatory Networks Marian Walhout, University of Massachusetts Medical School, USAHost: Anne-Claude GavinThe Operon, EMBL Heidelberg
Abstract: Gene regulation and metabolism lie at the heart of most biological processes. Both are accomplished by complex networks harboring hundreds of nodes and thousands of edges. We study these networks and the interactions between them mainly in the nematode C. elegans, because it is amenable to high-throughput, large-scale genetics and genomics. In addition, we study interspecies network interactions between C. elegans and bacteria, that may help illuminate interactions between mammalian intestinal cells and the gut microbiota.
EMBL Distinguished Visitor Lecture
Tuesday, 25 April 2017, 11:00Add to calendarThree short stories about sex chromosomes Job Dekker, University of Massachusetts Medical School, USAHost: Yad Ghavi HelmThe Operon, EMBL Heidelberg
Abstract: The 3D organization of the genome is critical for gene regulation. I will present three examples where sex chromosomes can serve as powerful models to study the folding of chromosomes in general, to identify cis-elements and proteins involved and to determine how chromosome organization and gene regulation are mechanistically linked.
Science and Society
Tuesday, 25 April 2017, 15:00Add to calendarEthical Review Goes Global: Learning the arts of a good ethical reviewRachel Douglas-Jones, IT University of Copenhagen, DenmarkHost: Halldór StefánssonLarge Operon, EMBL Heidelberg
EMBL Distinguished Visitor Lecture
Friday, 28 April 2017, 10:00Add to calendarSynaptic Processing of Visual Information in the RetinaLeon Lagnado, School of Life Sciences, , University of Sussex, Brighton, UK, United KingdomHost: Phil AvnerCNR Seminar Room, EMBL Monterotondo
Abstract:
Synapses are perhaps the most numerous computational elements within neural circuits. The process of chemical transmission can transform neural signals and, because synapses are plastic, these transformations can be altered over different time-scales to adjust the input-output relation of the circuit as a whole. I will describe experimental strategies that allow the synaptic basis of neural circuit function to be studied in vivo by imaging of genetically-encoded reporters. I will illustrate how these reporters can be used to analyze the synaptic processing of visual information in the retina of zebrafish. These strategies are revealing how the visual signal is first converted from an analogue format into spikes, as well as the synaptic changes that alter the input-output relation of the retinal circuit. In particular I will describe how plasticity of excitatory and inhibitory synapses can cause simultaneous increases and decreases in the gain of neural responses within distinct microcircuits of the inner retina. The general picture that emerges is one in which plasticity of synapses leads to dynamic changes in the encoding of visual stimuli.
External Faculty Speaker
Friday, 5 May 2017, 13:00Add to calendarDissecting bacterial lifestyle with systems-based approachesNassos Typas, EMBL Heidelberg, GermanyHost: Matthias WilmannsSeminar Room 48e, EMBL Hamburg
Abstract: We work at the interface of systems biology and molecular mechanism. On one hand we develop and utilize high-throughput quantitative approaches that reveal functional interactions between genes at a whole cell level. On the other hand, we zoom into these networks to understand how different functional modules are interconnected, often at a detailed mechanistic level. Here I will present how we use such approaches to shed light into gene function and pathway organization, to understand the action of drugs and their interplay when combined, and to probe how protein machineries operate at the bacterial cell envelope- how they are organized, how they coordinate their actions and how the cell senses when they are malfunctioning. We have also recently moved our approaches to the host-pathogen interface and the dynamic microbial communities formed in our gut. Our main goals are to: a) elucidate pathways Salmonella uses to hijack its host machinery and b) to probe how gut microbial communities are formed, how they react to nutrition and pharmaceuticals, and how their composition and characteristics affects our health.
External Faculty Speaker
Thursday, 11 May 2017, 11:00Add to calendarThe regulation of excitability within sensory neurons and pain pathogenesis: from molecule to manDavid Bennett, Nuffield Department of Clinical Neurosciences, University of Oxford, UK, United KingdomHost: Paul HeppenstallCNR Seminar Room, EMBL Monterotondo
Abstract: Neuropathic pain arises as a consequence of excessive excitability within sensory neurons. There has been significant progress over the last decade in understanding the molecular basis by which sensory neurons transduce and subsequently transmit noxious (ie. tissue damaging) stimuli giving rise to the sensation of pain. Over this same period we have recognized that mutations in such ion channels can result in primary pain disorders in humans providing great insight into the genetics of pain. An excellent example is the voltage gated ion channel NaV 1.7. Loss of function mutations in this ion channel result in congenital inability to experience pain and gain of function mutations can cause a number of distinct neuropathic pain disorders including erythromelalgia, paroxysmal extreme pain disorder and small fibre neuropathy. The fact that mutations in such channels can cause monogenic pain disorders makes them attractive analgesic drug targets and we are seeing a number of therapeutics being developed on this basis. Given that spontaneous activity is critical for the induction and maintenance of peripheral neuropathic pain we are now exploring techniques to reversibly silence sensory neurons. We have found that an engineered glutamate gated ion channel (which no longer responds to glutamate but is activated by Ivermectin) is very effective at electrically silencing sensory neurons both in vitro and in vivo. I will discuss how this can be used as a translational tool to reverse pain related hypersensitivity in animal models of neuropathic pain.
EMBL Distinguished Visitor Lecture
Friday, 12 May 2017, 10:00Add to calendarDNMT3A in Hematopoietic Stem Cells, Cancer and AgingMargaret Goodell, Baylor College of Medicine, Houston, Texas, USA, USAHost: Philip Avner / Christophe LancrinCNR Seminar Room, EMBL Monterotondo
Abstract: DNA methyltransferase 3a (DNMT3A) has recently emerged as an important tumor suppressor in hematologic malignancies, and its ablation in mouse hematopoietic stem cells inhibits differentiation. We will describe the use of DNMT3A knockout mice to study its role in myeloid and lymphoid malignancy development and its function in maintaining global DNA methylation. The role of DNMT3A mutations in intercellular competition in the context of aging will also be discussed.
External Faculty Speaker
Monday, 15 May 2017, 11:00Add to calendarTo be announced Katrin Rittinger, The Francis Crick Institute,Molecular Structure of Cell Signalling Laboratory,London, United KingdomHost: Esther OrtegaEMBL Seminar Room, EMBL Grenoble
EMBL - Sapienza Lecture
Friday, 19 May 2017, 11:00Add to calendarStructural dynamics of the breast cancer genome in response to hormonesMiguel Beato, Gene Regulation, Stem Cells and Cancer Program , Centre de Regulació Genòmica (CRG), The Barcelona Institute of Science and Technology, Barcelona , Spain, , SpainHost: Cornelius Gross / Irene BozzoniSapienza Università di Roma - Aula Odeion - Museo dell'Arte Classica - P.le Aldo Moro, 5 - Roma, EMBL Monterotondo
Abstract: Eukaryotic cells decode environmental information via receptors and signalling networks that converge in the cell nucleus to adjust an integrated gene expression response. We study the response of breast cancer cells to the steroid hormones estrogens and progesterone (Pg) acting via their respective receptors (ER and PR, respectively) to decipher the underlying molecular mechanisms.

The precise organization in nucleosomes of the DNA sequences recognized by PR is a requisite for receptor binding and the initiation of chromatin remodelling leading to displacement of histones H1 and H2A/H2B. Remodelling depends on receptor-associated enzymes, including histone modifying enzymes and ATP-dependent chromatin remodelers, as well as activated PARP1, which uses the NAD+ synthesized by NMNAT1 in the cell nucleus to synthesize large amounts of Poly-ADP-Ribose (PAR). These epigenetic processes are required for chromatin remodelling and the rapid regulation of thousand of genes leading ultimately to cell proliferation in response to hormone.

In addition to nucleosomes, higher levels of genome organization also participate in hormone action. The conserved partition of the genome in consecutive topological associating domains (TADs) contributes to coordination of the hormonal response. Hormone regulated genes tend to segregate into TADs that respond as a whole with either activation or repression of transcription. Genes in one TAD can be all activated by one hormone and all repressed by another hormone. Thus, TADs behave as regulons in the response of cells to external signals. High-resolution Hi-C data reveal the role of dominant enhancers in organizing the differential hormonal response within TADs.

The extensive chromatin remodelling observed in response to hormones requires the transient accumulation in the cell nucleus of large amounts of PAR, which is subsequently degraded to ADPR. A fraction of this ADPR is converted to ATP in the nucleus by NUDIX5 in the presence of PPi. NUDIX5 is a homodimer known to catalyse the hydrolysis of ADPR to AMP and R-5-P, but in response to hormone NUDIX5 is dephosphorylated at T45, leading to a conformational change of the homodimer that enables it to catalyse the reaction of ADPR with PPi to generate ATP and R-5-P. The ATP generated in the cell nucleus is essential for chromatin remodelling and gene regulation by estrogens or progesterone, as well as for DNA damage repair. NUDIX5 is overexpressed in breast cancers and is a marker for poor prognosis. Thus, it represents a novel target for breast cancer management.

Science and Society
Monday, 22 May 2017, 18:00Add to calendarMenschliche Gehirne aus dem Labor Fortschritte und Grenzen der modernen StammzellforschungJürgen Knoblich, Institut für Molekulare Biotechnologie, Wien, AustriaHost: Halldór StefánssonPrint Media Academy
EMBL Distinguished Visitor Lecture
Friday, 26 May 2017, 10:00Add to calendarTo be announcedSarah-Jayne Blakemore, Institute of Cognitive Neuroscience, UCL, London, UK, , United KingdomHost: Philip Avner / Cornelius GrossCNR Seminar Room, EMBL Monterotondo
Abstract: Tags: Neurobiology
Science and Society
Friday, 2 June 2017, 13:00Add to calendarTo be announcedMaureen O'Malley, University of Bordeaux, FranceHost: Rob MeijersSeminar Room 48e, EMBL Hamburg
EMBL Distinguished Visitor Lecture
Monday, 12 June 2017, 11:00Add to calendarTo be announcedWieland Huttner, MPI-CBG, Dresden, GermanyHost: Stefano De RenzisThe Operon, EMBL Heidelberg
Science and Society
Tuesday, 20 June 2017, 15:00Add to calendarCatastrophic Thinking: Extinction and the Value of DiversityDavid Sepkoski, Max Planck Institute for the History of Science, GermanyHost: Halldór StefánssonLarge Operon, EMBL Heidelberg
Abstract: Why do we care about preserving biodiversity? At the beginning of the 21st century biodiversity has come to be seen as an intrinsic scientific and cultural value. In other words, biological diversity the sheer multiplicity and heterogeneity of living things is now understood to have an inherent value that is not reducible to the utilitarian or aesthetic worth of any particular individual species: the value of diversity is diversity itself. Extinction plays a central role in this understanding of biodiversity, since diversity is something that is understood to be fragile and tenuous, constantly endangered by the threat of loss. Whereas most historians who have examined this phenomenon have placed the modern biodiversity movement in the context of a history of conservation biology and endangered species protection, I want to frame it in a new perspective. This talk will examine the influence of biological theories about the nature and dynamics of extinction and especially mass extinction on the current valuation of biological diversity. I will focus particularly on the ways that new understandings of extinction in the past for example, the extinction of the dinosaurs have converged with scientific and cultural anxieties about the present the specters of global warming, nuclear war, and biodiversity loss. I will argue that this new model of extinction has played a prominent conceptual and rhetorical role in debates surrounding the current biodiversity crisis, which I will examine in critical historical perspective.
External Faculty Speaker
Tuesday, 27 June 2017, 11:00Add to calendarTo be announcedMaria Carmo-Fonseca , University of Lisbon, PortugalHost: Isabel Chillon EMBL Seminar Room, EMBL Grenoble
External Faculty Speaker
Tuesday, 4 July 2017, 11:00Add to calendarTo be announcedEdward Lemke, EMBL Heidelberg, GermanyHost: Francesco BisiakEMBL Seminar Room, EMBL Grenoble
EMBL Distinguished Visitor Lecture
Thursday, 6 July 2017, 11:00Add to calendarTo be announcedOlivier Pourquié, Harvard Medical School, Department of Genetics/The Brigham and Women s Hospital, USAHost: Alexander AulehlaThe Operon, EMBL Heidelberg
EMBL Distinguished Visitor Lecture
Thursday, 14 September 2017, 11:00Add to calendarTo be announcedGene Myers, MPI-CBG, Dresden, GermanyHost: Stefano De RenzisThe Operon, EMBL Heidelberg
Science and Society
Friday, 29 September 2017, 11:00Add to calendarTo be announcedHelga Nowotny, ETH Zurich, Switzerland, SwitzerlandHost: Halldór Stefánsson CNR Seminar Room, EMBL Monterotondo
Abstract:
EMBL Distinguished Visitor Lecture
Friday, 6 October 2017, 10:00Add to calendarTo be announcedDouglas Higgs, MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United KingdomHost: Philip Avner / Christophe LancrinCNR Seminar Room, EMBL Monterotondo
External Faculty Speaker
Friday, 13 October 2017, 11:00Add to calendarTo be announcedAlla Karpova, HHMI Janelia Farm Research Campus, Virginia, USA, USAHost: Cornelius GrossCNR Seminar Room, EMBL Monterotondo
EMBL - Sapienza Lecture
Friday, 3 November 2017, 11:00Add to calendarTo be announcedAnne Ferguson-Smith, Department of Genetics, University of Cambridge, Cambridge , UK, United KingdomHost: Cornelius Gross / Irene BozzoniSapienza Università di Roma - Aula Odeion - Museo dell'Arte Classica - P.le Aldo Moro, 5 - Roma
Abstract:
EMBL Distinguished Visitor Lecture
Thursday, 9 November 2017, 11:00Add to calendarTo be announcedBing Ren, University of California, USAHost: Jan KorbelThe Operon, EMBL Heidelberg
EMBL Distinguished Visitor Lecture
Wednesday, 15 November 2017, 11:00Add to calendarTo be announcedDavid Baker, University of Washington, USAHost: Janosch HennigThe Operon, EMBL Heidelberg
EMBL Distinguished Visitor Lecture
Friday, 17 November 2017, 10:00Add to calendarEpigenetic mechanisms in early mammalian developmentMaria Elena Torres-Padilla, Institute of Epigenetics and Stem Cells (IES) , Helmholtz Zentrum München, GermanyHost: Philip Avner CNR Seminar Room, EMBL Monterotondo
Abstract: