Research Report - Nikolaus-Fiebiger-Zentrum für Molekulare Medizin

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Hematopoiesis Unit Chair of Genetics – Department Biology Head: Thomas Winkler, Dr. rer. nat. Professor for Genetics Address: Hematopoiesis Unit Glückstr. 6 D-91054 ERLANGEN Telefone: + 49 (9131) 85 29136 Fax: + 49 (9131) 85 29106 E-mail: thomas.winkler@molmed.rz.uni-erlangen.de Homepage: http://www.genetik.nat.uni-erlangen.de Ute Wellmann, Dr. rer. nat. * * part of the time reported Sven Brenner ° Agnes Giniewski Kristin Schröder ° PhD received Tanja Fisch* Markus Mroz* * part of the time reported Head Thomas Winkler, Prof. Dr. rer. nat. Professor for Genetics Postdoctoral Fellows Doctoral Students (Biology) Sonja Pötzsch ° Martina Seefried Technicians 49 Sabrina Sell Florian Weisel ° Andrea Schneider Hannes Tittlbach*
<strong>Research</strong> Our research focus lies on the selection processes at different stages of the development of B-lymphocytes. We investigate the genetic mechanisms for the early development of B-lymphocytes, the mechanisms for the loss of self-tolerance in the autoimmune disease systemic lupus erythematosus and antibody-mediated protection against cytomegalovirus. In our research we predominantly work with mouse models that we also create in our laboratory by the techniques of gene targeting (knock-out mice, knock-in mice, transgenic mice). B cell development and regulation of VDJ-recombination During the differentiation of B-lymphocytes the genes for the antibody molecules are assembled in a unique process called VDJ-recombination. VDJ-recombination is responsible for the enormous diversity of antibody molecules. This diversity is necessary to defend all possible invaders of our body. Whereas the molecular mechanism of the VDJ-recombination is understood in very much detail today, the regulation of this process is less well understood. All 7 different antigen-receptor gene loci (3 for immunoglobulins and 4 for T-cell-receptors) use the same VDJrecombination machinery, but still the expression of the different genes is tighly regulated. Antibody receptors are expressed only on B-lymphocytes and T-cell receptors only on T-lymphocytes. In addition, during development of B-lymphocytes the genes for the heavy chain of the immunoglobulin is recombined before the genes for the light chain and additional regulation exists that only one antigen-receptor is expressed on each B-lymphocyte. Our research focus is to investigate the accessibility of the immunoglobulin heavy chain genes for the VDJ-recombinase. The epigenetic mechanisms for the regulation of the chromatin state at the immunoglobulin loci is analyzed by modern methods (ChIP-on-ChiP, ChIP-Seq). In addition we try to identify the essential regulatory sequences at the immunoglobulin locus by gene-targeting. Regulation of VDJ-recombination in precursor B-lymphocytes Agnes Giniewski and Thomas Winkler VDJ recombination is strictly confined to the early precursors of T- and B-cells, where only T-cells recombine the T-cell-receptor loci and only B-cells recombine the B-cellreceptor loci. The differential regulation of VDJ recombination remains unknown as the Rag1 and Rag2 enzymes that are critical for this reaction are expressed in early B-cells as well as in early T-cells. It has been proposed, that the differentially regulated accessibility of the T- and B-cell receptor loci is the basis of this regulation. As chromatin accessibility is regulated by histone modifications, we generated a high 50
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Nikolaus-Fiebiger-Zentrum für Mole
Page 4 and 5: PREFACE Our present report covers t
Page 6 and 7: SCIENTIFIC ADVISORY BOARD The scien
Page 9 and 10: Financial Concept (Running Costs) R
Page 11 and 12: DEPARTMENT OF EXPERIMENTAL MEDICINE
Page 13 and 14: Research projects: I. Analyzing the
Page 15 and 16: osteoclast activity, we cannot rule
Page 17 and 18: Previously we have shown that cellu
Page 19 and 20: The proposed studies will provide n
Page 21 and 22: We recently introduced Ucma (Upper
Page 23 and 24: Park J, Bauer S, Schlegel KA, Neuka
Page 25 and 26: Research Hypertension is the primar
Page 27 and 28: accessory protein of the H+ vacuola
Page 29 and 30: Searle, J., Mockel, M., Gwosc, S.,
Page 31 and 32: DEPARTMENT OF EXPERIMENTAL MEDICINE
Page 33 and 34: Research Our group analyses molecul
Page 35 and 36: We found that the transcriptional r
Page 37 and 38: Fig. 1 Dual functional role of Amer
Page 39 and 40: HIF target gene expression in renal
Page 41 and 42: 2009 Wacker, I., Sachs, M., Knaup,
Page 43 and 44: Andreas Brandl* Sebastian Dütting*
Page 45 and 46: microRNAs in lymphocytes in health
Page 47 and 48: Function of EFhd1 and EFhd2 in B ce
Page 49 and 50: mainly expressed on phagocytes, fun
Page 51 and 52: Lang, V. R., Mielenz, D., Neubert,
Page 53: TRAINING OF GRADUATE AND MEDICAL ST
Page 57 and 58: During the last 3 years we had succ
Page 59 and 60: Adoptive transfer of memory B cells
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Page 63 and 64: passive immunization for prevention
Page 65 and 66: Weisel, F.J., U.K. Appelt, A.M. Sch
Page 67 and 68: IZKF Junior Group III BMBF Research
Page 69 and 70: Figure 1: Induced pluripotent stem
Page 71 and 72: oligomerizing mutant (α-syn mut, F
Page 73 and 74: INTERDISCILINARY CENTER OF CLINICAL
Page 75 and 76: Research Primary essential hyperten
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Page 79 and 80: its soluble receptor sVEGFR3). This
Page 81 and 82: Fig. 5. Selective blockade of the V
Page 83 and 84: 2011 Slagman MC, Kwakernaak AJ, Yaz
Page 85 and 86: Matrix Biology Group (Dpt. Of Inter
Page 87 and 88: Research Our group is mainly intere
Page 89 and 90: accumulation of collagen, dermal th
Page 91 and 92: Original Articles Publications (200
Page 93 and 94: 13. Krönke G, Uderhardt S, Kim KA,
Page 95 and 96: Reviews 1. Iwamoto N, Distler JH, D
Page 97 and 98: * PhD received Doctoral Students (M
Page 99 and 100: esidues, or nucleic acids. This sti
Page 101 and 102: Targeting antigens under immunizing
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Loschko J, Hackl D, Dudziak D, Rein
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Experimental Immunology and Immunot
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activating or inhibitory Fc recepto
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M and G levels. This was mirrored b
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orchestrates the clearance of apopt
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Grevers, L.C., van Lent, P.L., Koen
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Clinical Research Group (Reinhard V
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From the immunopathogenesis of syst
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with bortezomib depletes plasma cel
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Voll R, Hiepe F. [Depletion of plas
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Matthias Koch Franziska Cipa Melani
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application of both TSP-1 and OP-1
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Books and Reviews Gelse K, Beyer C.
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Stefan Fleischer Technicians Marina
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plain BCP constructs, constructs pr
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a source to establish a reliable pe
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Original Articles Rath SN, Strobel
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Research Our group is interested in
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essential regulatory mediators duri
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Fig. 3 The nuclear receptor PPARβ
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Books and Reviews Scholtysek C, Kr
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Elke Nolte geb. Löprich, Dipl. Bio
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prognosis and metastases of prostat
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Grochola LF, Taubert H, Greither T,
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DEPARTMENT OF INTERNAL MEDICINE 5 (
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Fig. 1 FACS analysis of NK cell sub
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Ullrich E, Bonmort M, Mignot G, Cha
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Tilman Jobst-Schwan Sina Grupp * pe
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comparison to the control animals.
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were able to induce the expression
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Figure 5: A. Kidney of a 7 months o
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protein is highly expressed in the
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and LOXL2 are necessary and suffici
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TEACHING ACTIVITIES at the Nikolaus
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G. Riemekasten, Berlin Systemic scl
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Research Report - Nikolaus-Fiebiger-Zentrum für Molekulare Medizin

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