Research Report 2010 - MDC

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Figure 3. Membrane resealing assay performed on wild-type mousesingle skeletal muscle fibres. Membrane damage (5x5µm) wasinduced with a two-photon confocal laser-scanning microscope (LSM510 META, Zeiss) coupled to a 488-nm Argon Ti:Sapphire Laser in thepresence of FM 1-43FX fluorescence dye. Top: Plot of fluorescenceintensity (n=10) against time in the presence (red line) and absence(black line) of Ca 2+ . Data are means +-SEM. Bottom: fluorescenceobtained in the presence (right) and absence (left) of Ca 2+ .Ahnak1 – a novel, prominent modulator of cardiacL-type Ca 2+ channelsHannelore Haase, Ines Pankonien, Karin Karczewski,Steffen Lutter (In collaboration with Nathan Dascal,University Tel Aviv, Israel)Ahnak1 is located at the sarcolemma and T-tubuli ofcardiomyocytes indirectly associated with the voltagedependentL-type Ca 2+ channel (L-VDCC) via its β2-subunit.The goal of this study will be understanding theinteractions of ahnak1 with L-VDCC, i.e. α1C and β2, andtheir modulation by β-adrenergic stimulation, mutations,and PKC activation (Figure 2). This will be achievedby heterologous expression of ahnak1 fragments inXenopus oocytes and HEK cells and the characterizationof their effects on cardiac and smooth muscle L-VDCC. Furthermore, reconstitution of β-adrenergicmodulation of L-VDCC in heterologous expression systems,and elucidation of the role of ahnak1, Cavβ andother signaling components in PKA and PKC modulationwill be studied.The functional role of the ahnak protein familyin adult skeletal muscle fibersAndreas Marg, Petra DomaingThe aim of the project is the elucidation of the role ofahnak protein family in skeletal muscle fibers. Thetransmembrane protein dysferlin seems to anchorahnak1 and ahnak2 to the sarcolemma, thus providing amembrane-stabilizing dysferlin-ahnak-actin complex.We investigate whether the ahnak protein family isimportant for membrane stability and Ca 2+ handling ofskeletal muscle fibers. A laser-assisted membraneresealing (Figure 3) and a Fura2-based fluorescenceassay of electrically stimulated enzymatically isolatedsingle skeletal muscle fibers from mouse Flexor digitorumbrevis will be applied.Identification of new adipocyte-derivedcardiodepressant factorsChristiane Look, Lena Martin (In collaboration withValeria Lamounier-Zepter, University Dresden)Recently, we showed that cultivated human adipocytesecrete factors which depress contraction of cardiomyocytes(Figure 4). The aim of this project is to identifyadipocyte-derived cardiodepressant factors. We willassess the role of different adipose tissue depots in producingthese cardiodepressant factors in our in vitroadipocyte/cardiomyocyte and adipocyte/isolated perfusedheart models. Finally, the adipocyte-derived cardiodepressantfactors will be analysed in vivo in microdialysissamples of subcutaneous adipose tissue ofobese patients as well as in serum of our obese patientcohort. The resulting data will allow the developmentof risk profiling and novel therapeutic strategies forheart dysfunction in obese patients.14 Cardiovascular and Metabolic Disease <strong>Research</strong>
Figure 4. Effect of adipocyte-conditionedmedium (AM) on shorteningamplitude (top trace) and Fura-2signal (bottom trace) of an adultrat cardiomyocyte. A, B)Representative chart recordings ofshortening amplitudes.Selected PublicationsLamounier-Zepter V, Look C, Alvarez J, Christ T, Ravens U, Schunck W-H,Ehrhart-Bornstein M, Bornstein SR, Morano I (2009) Adipocyte fatty acidbindingprotein suppresses cardiomyocyte contraction: a new linkbetween obesity and heart disease. Circ Res. 105:326-34.Tünnemann, G, Behlke, J, Karczewski, P, Haase, H. Cardoso, MCh, Morano, I.(2007). Modulation of muscle contraction by a cell permeable peptide. JMol Med.12:1405-12.Aydt EM, Wolff G, Morano I (2007) Molecular modelling of the myosin-S1(A1) isoform. J. Struct. Biol., 159:158-63.Haase H, Dobbernack G, Tünnemann G, Karczewski P, Cardoso C, PetzholdD, Schlegel WP, Lutter S, Pierschalek P, Behlke J, Morano I. (2006)Minigenes encoding N-terminal domains of human cardiac myosin lightchain-1 improve heart function of transgenic rats. FASEB J. 20:865-73.Haase H, Alvarez J, Petzhold D, Doller A, Behlke J, Erdmann J, Hetzer R,Regitz-Zagrosek V, Vassort G, Morano I. (2005) Ahnak is critical for cardiacCa(V)1.2 calcium channel function and its beta-adrenergic regulation.FASEB J. 19:1969-77.Patent applications„Behandlung der Dysfunktion der Herzkontraktilität oderHerzinsuffizienz, insbesondere bei übergewichtigen und adipösenPatienten mittels Hemmung von FABP4“. P1880EPCardiovascular and Metabolic Disease <strong>Research</strong> 15
Page 1: Research Report 2010MAX DELBRÜCK C
Page 4 and 5: ContentInhaltContentInhalt.........
Page 6 and 7: Surgical OncologyPeter M. Schlag...
Page 11 and 12: at the MDC. The role of the institu
Page 13 and 14: in discovering genes that contribut
Page 16 and 17: The ECRC offers research space and
Page 18 and 19: etween disciplines such as biology,
Page 20 and 21: approaches from bioinformatics/syst
Page 23 and 24: von Humboldt Foundation (AvH). The
Page 25: organization to a larger, multi-fac
Page 28 and 29: Cardiovascular and Metabolic Diseas
Page 30 and 31: electrical signals. More recent wor
Page 32 and 33: Basic Cardiovascular FunctionStruct
Page 34 and 35: Figure 2: SORLA and sortilin in neu
Page 36 and 37: Annette Hammes(Delbrück Fellow)Str
Page 38 and 39: Ingo L. MoranoStructure of the Grou
Page 42 and 43: Michael GotthardtStructure of the G
Page 44 and 45: Structure of the GroupSalim Seyfrie
Page 46 and 47: Structure of the GroupFerdinand le
Page 48 and 49: Francesca M. SpagnoliStructure of t
Page 50 and 51: Structure of the GroupKai M. Schmid
Page 52 and 53: Genetics and Pathophysiology of Car
Page 54 and 55: Figure 2. Planariato experimentally
Page 56 and 57: Norbert HübnerStructure of the Gro
Page 58 and 59: Structure of the GroupGroup LeaderF
Page 60 and 61: Figure 2. Omega-3 fatty acids prote
Page 62 and 63: Structure of the GroupDominik N. M
Page 64 and 65: Rainer DietzStructure of the GroupG
Page 66 and 67: Figure 2. Cardiac-restricted ablati
Page 68 and 69: Ludwig ThierfelderStructure of the
Page 70 and 71: standing of the molecular and cellu
Page 72 and 73: Structure of the GroupThoralf Niend
Page 74 and 75: Michael BaderStructure of the Group
Page 76 and 77: Natriuretic peptide systemJens Butt
Page 78 and 79: Structure of the GroupZsuzsanna Izs
Page 80 and 81: Young-Ae LeeStructure of the GroupG
Page 82 and 83: Structure of the GroupMatthias Selb
Page 84 and 85: Matthew PoyStructure of the GroupGr
Page 86 and 87: Jana WolfStructure of the GroupGrou
Page 88 and 89: Structure of the GroupGroup LeaderD
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Cancer Research ProgramKrebsforschu
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are responsible for the emergence o
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tral component of the canonical Wnt
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lead to an aberrant constitutive ac
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How Notch- and TGFβ signaling casc
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tures of the chronic phase in human
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oped a new safeguard that is based
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Graduate StudentsSeda Cöl ArslanCa
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investigation, as is the cause of c
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Graduate StudentsÖzlem Akilli Özt
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onment, the (cancer) stem cell nich
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The pluripotent state of murine and
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In the morula of the early mouse em
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Graduate StudentsRami Hamscho*Qingb
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esis and granulopoiesis. We showed
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URE ∆/∆ mice regularly develope
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PD Dr. Wolfgang Walther (GroupLeade
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For the delivery of naked DNA into
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ACBDMyc and FoxO transcription fact
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Graduate StudentsKatrin BagolaHolge
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Heinemann, we could also identify t
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Above: Tip of chromosom3L showing t
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Graduate StudentsSarbani Bhattachar
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vesicle transport to the Golgi. Our
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acbFigure 1a: EHD2 is tubulatingpho
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KnowledgeProbabilitiesknownPossible
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Graduate and undergraduatestudentsU
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successive oncogenic mutations. We
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CXCR5 drives the development of ect
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Graduate and undergraduatestudentsW
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Graduate andUndergraduate StudentsM
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Angela MensenStefanie WittstockBjö
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deficient mice, both major effector
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ant of CD3 delta coding for a 45-me
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Robert KudernatschLi-Min LiuAna Mil
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Sebastian GüntherTechnical Assista
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Graduate StudentsJana RolffAnnika W
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with murine hepatocytes showed morp
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Function and Dysfunction of the Ner
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The Neuroscience Department also es
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the coming years, Björn Schröder
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mice. Further analysis of the funct
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Signaling Pathways and Mechanisms i
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Control Olig3 -/-ABFigure 2. Geneti
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Thomas J. JentschStructure of the G
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Figure 2. Cellular model for ionic
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Structure of the GroupGroup LeaderF
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paired-pulse facilitation, less dep
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Gary R. LewinStructure of the Group
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Model summarizing the three waves o
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Structure of the GroupInes Ibañez-
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Jochen C. MeierStructure of the Gro
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Björn Christian SchroederStructure
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Structure of the GroupJan Siemens(S
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Structure of the GroupGroup LeaderD
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Imaging of the Living BrainStructur
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Pathophysiological Mechanisms of Ne
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Figure 2. Iba1 positive microglia c
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Erich E. WankerStructure of the Gro
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Scientific-Technical StaffAnja Frit
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Structure of the GroupJan Bieschke(
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Berlin Institute of Medical Systems
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etes, metabolic diseases and neurod
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A number of MDC investigators have
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Technical AssistantsClaudia Langnic
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has become a standardized data flow
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Phylogeny of cellulase genes from P
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Experimental and Clinical Research
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his patients, and a basic research
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The ultrahigh field MR facility was
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Structure of the GroupSimone Spuler
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Ralph KettritzStructure of the Grou
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Structure of the GroupJeanette Schu
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Maik GollaschStructure of the Group
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Technology PlatformsComputational B
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projects/ard/] to detect repeats li
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Simulation of line-scan images of C
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Development of an MRM method for qu
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mobility or turnover of the underly
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Left: Inside view of a FACSAria2 (f
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Examples fort the use of EM methods
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Oviducts lined up in pre-implantati
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Academic Appointments 2008-2009Beru
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Buch which is part of the Excellenc
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“Bioinformatics in Quantitative B
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Delbrück FellowsDelbrück-Stipendi
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Yinth Andrea Bernal-Sierra, a PhD s
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Congresses and Scientific MeetingsK
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SeminarsSeminare2008Speaker Institu
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Speaker Institute TitleKiyoshi Mori
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2009Speaker Institute TitleDavid G.
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Speaker Institute TitleJuri Rappsil
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The Helmholtz AssociationDie Helmho
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The Berlin-Buch CampusDer Campus Be
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the MDC, the existing collaboration
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Prof. Dr. Gary R. LewinMDC Berlin-B
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Prof. Dr. Renato ParoCenter of Bios
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Staff CouncilThe Staff Council is i
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Type of Financing/Art der Finanzier
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Research Projects 2008-2009Forschun
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CIC-5 Regulation und Endocytose am
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MDCMAX-DELBRÜCK-CENTRUMFÜR MOLEKU
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Index 275Bröske, A. . . . . . . .
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Index 277Gross, V. . . . . . . . .
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Index 279Kur, E. . . . . . . . . .
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Index 281Piano, F. . . . . . . . .
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Index 283Smink, J. . . . . . . . .
Page 312 and 313:
Campus MapCampusplanRobert-Rössle-
Page 314:
How to find your way to the MDCDer
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